JP2016519054A - Composition comprising mannoheptulose for use in the treatment or prevention of overweight and obesity - Google Patents

Abstract

The present invention is based on the discovery that mannoheptulose (mHep) reduces the body's fat storage capacity by reducing or inhibiting the differentiation process from adipose stem cells to adipocytes. Compositions comprising mHep, processes for making the compositions, and compositions for treating or preventing overweight and obesity in mammals such as growing pets (eg puppies, kittens) or ovariectomized / castrated pets The method of using is included in the present invention.

Description

  The present invention relates to a method of treating or preventing overweight and obesity in a mammal comprising administering to the mammal a composition comprising an effective amount of mannoheptulose (mHep). Furthermore, the present invention also includes compositions comprising mHep and processes for making the compositions.

Overweight and obesity are a major problem in mammals, particularly humans and livestock, such as pets (eg dogs, cats). According to the US Centers for Disease Control (CDC), approximately one-third (33.3%) of all adults in the United States are overweight (ie BMI = 25 kg / m ² to 29.9 kg / m ² ). Numbers greater than a fraction (35.7%) are obese (ie, BMI ≧ 30 kg / m ² ). Unfortunately, pets are not healthier than their owners. According to 2011 statistics from the Pet Obesity Prevention Association (APOP), 53% of adult dogs and 55% of adult cats are overweight or obese in the United States (similar scoring system and IAMS®) (Based on a body condition chart (BCS) to assess obesity in cats and dogs developed by Greg Sunvold (1998)).

  The important point is that whether humans and livestock are considered overweight or obese is not by weight but by percentage of body fat. Overweight and obesity are the accumulation of excess adipose tissue (ie body fat) due to, for example, excessive caloric intake and / or lack of exercise. Excess accumulation of body fat occurs when the amount of fat (eg, triglycerides) synthesized and deposited in fat cells exceeds the amount of fat breakdown. Over time, such excessive accumulation of body fat becomes overweight and then obese if left untreated.

  Being overweight or obese clearly increases morbidity and mortality. Furthermore, many health problems may be exacerbated alone and in combination with other diseases. For example, if an overweight or obese dog is left untreated, particularly in an adult dog (ie about 6 to 8 years old) or an old dog (ie about 9 years old or older), chronic diseases such as diabetes, cancer, The risk of developing hypertension, pulmonary disease, cardiovascular disease or osteoarthritis increases, so the quality of life may decrease. That is, the advantage of not being overweight or obese includes not only longevity but also high quality of life. Older dogs are further disadvantaged by the fact that they are prone to “age related body fat gain” which may contribute to becoming overweight or obese. Thus, there is still a need for new or advanced methods for treating or preventing overweight and obesity in mammals, particularly when the mammal is an aging pet.

  In addition to the role of adipose tissue as a reserve of surplus energy (ie fat) for the body, it has been recognized as an endocrine organ that produces hormones, such as estrogen, a sex hormone. Estrogens are present in both male and female animals. It plays an important role in regulating the function and development of adipocytes forming adipose tissue and maintaining normal body adipose tissue (Non-patent Document 1). In fact, in humans, a decrease in estrogen levels after menopause and after pet ovariectomy / castration surgery for population control reasons has been correlated with increased accumulation of adipose tissue (body fat) (non-patented Document 2; Non-patent document 1; and Non-patent document 3).

  Estrogens mediate their effects on adipose tissue in a wide variety of ways. For example, estrogen affects the number and size of adipocytes; regulates the rate of adipogenesis and lipolysis; and may increase appetite or reduce energy expenditure (Non-Patent Document 2; Non-Patent Document 1; And Non-Patent Document 4). Hormone replacement therapy and estrogen dietary supplementation are common methods that attempt to stop these effects (Non-Patent Document 5). However, both therapies are expensive and require strict patient compliance in order for them to be effective.

  Thus, there is still a need for new or advanced methods of treating or preventing overweight or obesity in mammals that may be due to, for example, menopause in humans or weight gain from animal ovariectomy / castration surgery, and in particular The method minimizes additional costs and facilitates patient / animal compliance. For example, if mHep is pre-mixed in a pet food composition, treatment can be achieved simply by eating the animal.

  Consumers believe that the health and longevity of their pets can be achieved through a combination of proper nutrition from high-quality diets, ovariectomy and castration, maintenance of an active lifestyle, and regular veterinary visits. Yes. In response to such nutritional requirements in pet food, the pet food industry is exploring the use of caloric restriction mimetics as a sales strategy. Caloric restriction is believed to result in an increase in median lifespan (ie, the age at which 50% of the population is alive) and longevity (ie, the age of the longest surviving individual). According to recent studies, the amount of time that an animal's life span is extended gradually increases as caloric intake decreases and the duration of a calorie restricted diet increases. In one study, monkey life spans have increased by over 30% because they started caloric restriction soon after birth (Non-Patent Document 6). Furthermore, a 10% to 40% reduction in caloric intake has also been found to be effective in improving quality of life by delaying and / or preventing age-related diseases.

  An example of a calorie restriction mimetic is mannoheptulose (mHep), which is a 7-carbon sugar present in various natural sources such as avocado, fig and primula. mHep is believed to be effective for life extension and quality of life in both lower and higher organisms. As a calorie restriction mimetic, mHep competes with glucose due to its structural similarity and binds to hexokinase-1, an enzyme in glycolysis. As a result, glucose metabolism is suppressed and fatty acid synthesis is prevented. This reduces the amount of fat deposition in the fat cells, which ultimately leads to weight loss. In a related role, mHep may block the normal metabolism of carbohydrates by functioning as a glucose antimetabolite. The resulting physiological changes may include lower tissue glucose levels, lower plasma insulin levels, and weight loss (see US Pat. Both effects are due to mHep's inhibition of carbohydrate metabolism. To date, mHep has not been shown to affect adipocyte expression or activity, and is not particularly associated with overweight and obesity.

  In view of the growing problem associated with excessive weight gain in today's human and pet populations, new or advanced methods of treating and preventing overweight and obesity in mammals are still desirable. In certain embodiments, the mammal is caused, for example, by changes in hormone homeostasis (ie, menopausal humans and ovarectomy / castrated surgical pets) or from normal age-related weight gain (ie, elderly or old pets). It is preferably selected from a subgroup with a high risk of steatosis that occurs, especially if the animal is otherwise healthy.

International Publication No. 2012 / 61446A1

Cooke, P.A. S. Et al., Exp. Biol. Med. , 229: 1127-35, 2004. Pergola, G. et al. D. , Int. J. et al. Obesity, 24: S59-S63, 2000 Mohamed, M.M. K. Et al., Eur. J. et al. Endocrinol. 142: 307-14,2000 Naaz, A .; Et al., Endocrinology 144: 3315-20, 2003. Sayegh, R.A. A. , Etc. Meopause 6: 312-5, 2002 Mattson, M.M. P. J. et al. Nutr. Biol. 16, 3: 129-137, 2005

  New or advanced methods preferably apply to growing pets when they are overweight or obese or have undergone oophorectomy / castration surgery before reaching sexual maturity. It would also be desirable to be profitable. Alternatively, early administration of mHep to growing pets exposes the animal to calorie restriction mimetics for a longer period of time, thereby increasing the chance of extending lifespan in these animals.

  In a first aspect, the present invention relates to a new use of mHep based on the discovery of various molecular processes and mechanisms that mHep provides new benefits to mammals. The present inventors have found that mHep suppresses the differentiation of adipose stem cells into adipocytes, thereby reducing the body's fat storage capacity through a reduction in adipocyte mass. Furthermore, mHep has also been found to inhibit adipocytes from exhibiting adipogenic or lipogenic effects that can result in excessive buildup of adipose tissue that contributes to weight gain. With this discovery, the inventors have discovered a new method of using mHep for treating or preventing overweight and obesity in a mammal, the method comprising administering to the mammal a composition comprising an effective amount of mHep.

  In one embodiment, the method relates to a mammal that is a pet, and more particularly a pet is (a) a growing pet that may have been overweight or obese, unfertile, or ovariectomized / castrated (eg, Pups, kittens); (b) adult pets that may have been overweight or obese, unreproductive, or ovariectomized / castrated; or (c) overweight or obese, unreproductive, or ovariectomized / castrated Selected from old pets that may have been operated on.

  In another embodiment, the method comprises administering to the mammal a composition comprising an amount of mHep effective to inhibit or reduce the differentiation process from adipose stem cells to adipocytes in the mammal, whereby the mammalian Body fat storage capacity is reduced by about 5% or more, about 10% or more, or about 20% or more compared to an untreated mammal.

  In yet another embodiment, the method comprises providing to the mammal a composition comprising a daily dosage of about 1 mg / kg to about 50 mg / kg of mHep, the composition comprising pet food, supplements and liquids The supplement or liquid is selected from the group consisting of and can be taken individually or added to the pet food. The composition may be a hydrous composition (ie, having a total moisture content greater than 50% by weight of the product), a wet composition (ie, having a total moisture content of from about 16% to about 50% by weight of the product), semi-wet It can be selected from the group consisting of compositions, dry compositions and combinations thereof. The composition can be a nutritionally balanced pet food composition.

  In another aspect, the invention relates to the life of a mammal, preferably a growing pet, such as a puppy or kitten, by administering to the mammal a composition comprising an effective amount of mHep to reduce caloric intake of young pets. Where the administration begins in the range of about 1 to 3 years after the animal's birth. The reduction in caloric intake is preferably in the range of about 10% to about 50% of caloric intake prior to administration.

  In yet another aspect, the invention relates to a pet food composition comprising an amount of mHep effective to promote or maintain healthy body fat in a growing pet, wherein the mHep is from about 0.0001% by weight of the composition. It is present in the composition at about 10% by weight. The pet food composition is preferably a high fat food composition, wherein the fat content present in the composition is from about 15% to about 45% by weight of the composition. Higher fat content brings greater palatability to the pet food composition, but mHep minimizes and / or offsets any negative effects on weight gain.

  These and other features of the present invention will become apparent to those skilled in the art when the following detailed description is considered in conjunction with the appended claims.

While the specification concludes with claims that particularly point out and distinctly claim the invention, the invention should be better understood from the following description of the accompanying drawings.
Physical condition chart for assessing obesity in dogs. A physical condition chart for evaluating obesity in cats. Oil staining showing inhibition of MSC differentiation by mHep.

Definitions As used in this specification, the singular forms used in the claims shall include the plural forms.

  Within the scope of the present description, the term “about” is optionally ± 20%, preferably optionally ± 10%, more preferably optionally ± 5%, even more preferably optionally ± 2%, and Most preferably, it is sometimes taken to mean ± 1%.

  As used herein, the term “including” means non-limiting.

“Obesity” as used herein means an increase in weight that exceeds the limits of skeletal and physical needs as a result of excessive body fat accumulation. A human is “obese” if it has a body mass index (BMI) greater than 30 kg / m ² according to US CDC guidelines. Pets such as cats or dogs, for example, are shown in a physical condition chart (BCS) for assessing obesity in cats and dogs developed by “IAMS” Greg Sunvold (1998), and FIG. 1A (dogs) and When the guidelines reproduced in 1B (cat) are used, if an animal has its physical attributes, it is identified as “obese”. For all other types of mammals, similar body condition charts and scoring systems, such as the Body Condition Score, are used to obtain guidance for determining whether a subject is “obese” it can.

“Overweight” as used herein means having a normal or more body weight than necessary, particularly having a body weight that is more than normal or healthy for an individual's age or physique. Human is "overweight" as having According to US CDC guidelines 25.0 kg / ^{m 2} from 29.9 kg / ^{m 2} Body Mass Index (BMI). Pets such as cats or dogs, for example, are shown in a physical condition chart (BCS) for assessing obesity in cats and dogs developed by “IAMS” Greg Sunvold (1998), and FIG. 1A (dogs) and When the guideline reproduced in 1B (cat) is used, if an animal has the physical attribute, it is identified as “overweight”. For all other types of mammals, similar body condition charts and scoring systems can be used to obtain guidance for determining whether a subject is “obese”.

  “Mammal” as used herein means a primate, such as a human, ape or monkey, or a domestic animal, such as a pet.

  “Pet” as used herein is a domestic animal, such as a domestic dog (canine), cat (feline), horse, cow, ferret, rabbit, pig, rat, mouse, gerbil, hamster. Means horses, etc. Pets are also referred to herein as “companion animals”.

  “Growing pet”, as used herein, refers to a subset of “pets” and includes young animals that are still developing and not sexually mature.

  “Kitten” as used herein refers to a kind of “growing pet” and includes domestic cats that are 3 years old or younger, or about 2 years old or younger, or about 1 year old or younger To do.

  “Puppy” as used herein refers to a kind of “growing pet” and includes domestic dogs 3 years old or younger, or about 2 years old or younger, or about 1 year old or younger To do.

  “Adult pet”, as used herein, refers to a subset of “pets”, such as domesticated dogs (canine) and cats (feline) between about 3 years of age and about 8 years of age. ).

  “Old-aged pet” as used herein refers to a subset of “pets” and includes, for example, domesticated dogs (canine) and cats (feline) over 9 years of age.

  “Non-fertile” as used herein means that an animal can still breed because it has not received any treatment to remove or neutralize the genitals (eg, ovary, testis).

  “Menopause” as used herein means a period of permanent cessation of menstruation in female humans, typically occurring between about 45 and about 55 years old. Menopause is characterized by dramatic changes in hormone levels, such as a decrease in estrogen levels because the ovaries are no longer producing eggs.

  “Ovariectomy” or “castration” as used herein means a surgical procedure performed on an animal to adjust the population. “Neuter surgery” is the removal of the testis from male animals, and “ovariectomy” is the removal of the ovaries from female animals. “Ovariectomy” or “castration” is also a low circulating blood due to natural causes such as anatomical defects, biochemical or genetic abnormalities, or due to disease, eg compared to healthy non-obese control animals. It can also include pets that have undergone changes with regard to their genitals due to male pauses with low levels of medium estradiol.

“Treatment” or “treatment” as used herein means treating an overweight and obese condition in a mammal, including:
(I) suppressing overweight and obese conditions, ie stopping its onset;
(Ii) alleviating an overweight and obese condition, i.e. inducing a regression in an overweight or obese condition; or
(Iii) alleviating symptoms resulting from an overweight or obese condition, ie, alleviating an overweight or obese condition without targeting the underlying cause of the disease or condition;
Is included.

  “Prevent”, as used herein, means to stop an overweight and obese condition from occurring.

  “Relieving” as used herein means being able to tolerate overweight and obese conditions.

“Healthy body weight” as used herein means a range of body weight that is considered healthy. This can be determined by a body mass index (BMI) based on height and weight. According to the US CDC guidelines, BMI range associated with normal body weight is 24.9 kg / ^{m 2} from 18.5 kg / ^{m 2.}

  “Healthy body fat” as used herein means the age-adjusted percentage of body fat that is considered healthy for mammals. Healthy body fat includes (i) essential body fat and (ii) storage body fat. Essential body fat is necessary to maintain vital functions and reproduction of life. Stored body fat consists of an accumulation of fat in adipose tissue. The present invention is intended to limit the percentage of stored body fat to minimize adverse weight gain.

  “Adipose-derived stem cells” or “adipose stem cells” as used herein means pluripotent cells that can differentiate into tissue cells such as adipocytes (ie fat cells). They are ubiquitous and are present in adipose tissue. The adipose stem cells are “adipose-derived adult stem (ADAS) cells”, “adipose-derived stromal cells (ADSC)”, “adipose stromal cells (ASC)”, “adipose mesenchymal stem cells (AdMSC)”, “pre-adipocytes” ”,“ Treated lipid aspirated (PLA) cells ”and“ adipose-derived stromal / stem cells (ASC) ”.

  “Adipocyte” as used herein means a cell specialized in storing energy as fat for the body and is a primary cell that constitutes adipose tissue. “Adipocytes” are also known as “lipocytes” and “fat cells”.

  “Adipose tissue” as used herein means connective tissue comprising adipocytes (ie, fat cells). Adipose tissue is generally where the body deposits and stores excess fat. Adipose tissue includes, but is not limited to, white, brown and yellow adipose tissue.

  “Body fat storage capacity” as used herein means the body's ability to store energy as fat for the body in adipose tissue. Body fat storage capacity increases with increasing number of adipocytes.

  In this specification, reference is made to trade names relating to elements including various components utilized in the embodiments of the present invention. The inventors do not intend to limit the substance to a specific trade name. Substances equivalent to those mentioned under the trade name (eg, those obtained from different sources under different names or reference numbers) may be substituted and utilized in the description herein.

In particular, compositions comprising mannoheptulose (mHep) provide compositions comprising an effective amount of mHep for treating overweight and obesity in mammals. In one embodiment, the composition of the present invention is a food composition intended for oral consumption by mammals, preferably humans or pets (eg cats, dogs). In a particular embodiment, the composition is intended for consumption by a pet, in which case the composition is selected from the group consisting of pet food, supplements and liquids.

  A “pet food” is a composition intended to be ingested by a pet, preferably a domestic pet, such as a cat, kitten, puppy, or dog. As used herein, “pet food” is intended to encompass confectionery (eg, biscuits), chews, rawhides and the like. In some embodiments, “pet food” is specifically designed for growing pets (eg, puppy food), or in other embodiments, “pet food” is “complete and nutritionally balanced”. Pet food. This contains all known necessary nutrients in appropriate amounts and proportions based on the recommendations of authorities recognized in the field of pet nutrition, and thus life without the addition of supplemental nutritional ingredients. Can be the only source of food intake to maintain or promote reproduction. For examples of “nutritionally balanced” dog foods, see National Research Council, 1985, Nutritional Requirements for Dogs, National Academy Press, Washington D. et al. C. Alternatively, reference can be made to the Guidelines of Association of American Feed Control Officials, Official Publication 1996).

  In another embodiment, the pet food composition is a dry composition (eg, rough grain, having a total moisture content of about 0% to about 16% by weight of the product), a wet or semi-moist composition (ie, Product having a total water content of about 16% to about 50% by weight of the product), a water-containing composition (ie having a total water content of greater than about 50% by weight of the product), or a mixture thereof.

  In yet another embodiment, the pet food composition is on a dry matter basis a) about 15% or more of the composition; b) about 25% or more of the composition; c) about 35% or more of the composition; or d) may be a “high fat food”, preferably a “high fat pet food” having a fat content present in a pet food composition of about 45% by weight or more of the composition. It is common practice to intentionally add some fat to a pet food composition to improve palatability. However, if the amount of fat begins to exceed 10% of the pet food composition, the pet food is considered “high fat” for the consumer. High fat pet foods are difficult to sell because the general consumer prefers low fat substitutes that provide the correct nutritional balance for their pets.

  Without being bound by theory, for example, in the case of high-fat pet food compositions, adding an effective amount of mHep to the high-fat pet food composition will cause mHep to interact with fat cells and negate the negative effects of fat It is done. Adding higher concentrations of mHep to increasing concentrations of fat to a level such that the effect of the presence of high fat content of the pet food composition on the body fat accumulation of food consuming animals is minimized or eliminated. Can do. In certain embodiments, mHep is believed to be effective in reducing negative effects, even at very high levels of fat content, for example, greater than about 45% by weight of the composition.

  Embodiments related to the compositions of the present invention, preferably pet food compositions, may further comprise a carbohydrate source. In one embodiment, the composition may comprise a carbohydrate source from about 35% by weight of the composition to about 50% by weight of the composition. In other embodiments, the composition can comprise from about 35% to about 45% by weight of the composition or from about 40% to 50% by weight of the composition of carbohydrate source. Non-limiting examples of carbohydrate sources include grains or cereals such as rice, corn, milo, sorghum, barley, wheat, etc., which are representative examples of carbohydrate sources.

  The composition of the present invention, preferably a pet food composition, also includes other substances such as, but not limited to, dried whey and other dairy by-products, beet pulp, cellulose, fiber, fish oil, flax, vitamins, minerals , Fragrances, antioxidants and taurine.

  Optionally, other advantageous ingredients such as crude protein are also present from about 10% to about 90% by weight of the composition, from about 20% to about 50% by weight of the composition, from about 20% by weight of the composition. It may be present in a composition of the present invention, preferably a pet food composition, as a percentage of the composition up to about 40% by weight, or ranging from about 20% to about 35% by weight of the composition. Other optional ingredients in the pet food composition include probiotic ingredients (bifidobacteria and / or lactobacilli), prebiotic ingredients (eg fructooligosaccharides, see eg PCT publication WO 2005/0158294), omega-6 and Omega-3 fatty acids, carnitine, hexametaphosphate, glucosamine, chondroitin sulfate, carotenoids such as beta carotene, vitamin E and lutein may be included.

  “Supplement” as used herein is intended to cover both “dietary supplements” and “food supplements” and is taken individually in addition to the normal diet in mammals. Means a product intended to be added to a feed, preferably a pet food, or to a liquid intended for consumption by animals.

  “Liquid” as used herein means fillers, grevies, sauces, beverages, supplement water, and combinations thereof. The liquid is intended to be ingested separately in addition to the mammal's normal diet or added to feed, preferably pet food.

Mannoheptulose (mHep)
The compositions of the present invention comprise an effective amount of mHep for treating or preventing overweight and obesity in a mammal receiving the composition. When the composition is preferably a pet food, the amount of mHep as a percentage of the composition is about 0.0001% to about 10% by weight of the composition, about 0.1% to about 5% by weight of the composition. %, Or in the range of about 0.1% to about 3% by weight of the composition, wherein the weight of the composition is on a dry matter basis.

  It should be noted that higher percentages of mHep may be supplied because of other caloric restriction mimetics such as having high effective doses but strong cytotoxicity (50-100 μm) This is because, unlike resveratrol, which is more difficult to administer, the therapeutic concentration range of mHep is wide. In various other embodiments, the amount of mHep is about 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5% by weight of the composition. 4.0 wt%, 4.5 wt%, 4.0 wt%, 4.5 wt%, 5.0 wt%, 5.5 wt%, 6.0 wt%, 6.5 wt%, 7 0.0%, 7.5%, 8.0%, 8.5%, 9.0%, 9.5%, or 10.0%.

  When formulating the composition as a dietary supplement, it may be easily administered to a mammal in the form of a tablet, capsule, concentrate or other similar dosage form, or diluted, for example with water, Increase mHep at higher concentrations (ie, 2x, 3x, 4x, 5x, etc.) so that the composition can be diluted prior to administration by spraying or spreading onto pet food and other similar modes of administration. It may be formulated to contain.

The mHep used in the present invention can be derived from any suitable raw material. Preferred sources of mHep are as follows:
i. Naturally derived mHep raw material;
ii. Synthetically derived mHep raw material;
iii. MHep raw material derived from microorganisms;
iv. a) and b) in combination;
v. a) and c) in combination;
vi. a combination of b) and c);
vii. a), b) and c) combinations;
Is included.

Naturally derived mHep
mHep may be obtained from "naturally occurring raw materials" such as components of plant materials such as avocado, avocado extract, avocado flour, avocado concentrate, or other mHep enriched raw materials. Non-limiting examples of mHep reinforcing ingredients include alfalfa, fig or primula. The plant material may include fruits, seeds (or nuclei), branches, leaves, or any other part of the plant, or a combination thereof.

  Avocado (commonly referred to as alligator pier, aguacate, or parta) contains mHep and a very rich source of related sugars and other carbohydrates. Avocado is the subtropical evergreen fruit that is best cultivated in California, Florida, Hawaii, Guatemala, Mexico, West India, South Africa and Asia.

  Avocado species include, for example, Persea Americana and Persea nubigena, and all cultivated variant plants of these representative species. Cultivated variety plants are “Anaheim”, “Bacon”, “Creamhart”, “Duke”, “Fuerte”, “Ganter”, “Gwen”, “Hass”, “Jim”, “Lula”, “Lyon”, “Mexicola” “Grande”, “Murrieta Green”, “Nabal”, “Pinkerton”, “Queen”, “Puebla”, “Reed”, “Rincon”, “Ryan”, “Spinks”, “opa Topa”, “Whitsell” “Wurtz” and “Zutano” may be included. Particularly preferred for use in the present invention are avocado fruits that contain nuclei, or from which nuclei have been removed or at least partially removed. Persea Americana fruits, as well as cultivated varieties that produce larger fruits (eg, about 12 ounces or more when the fruits are ripe), such as Anaheim, Creamhart, Fuerte, Hass, Lula, Lyon, Murrieta Green, Nabal, Queen, Puebla, Reed, Ryan and Spins fruits are particularly preferred for use in the present invention.

  Other examples of natural sources of mHep may include plant material obtained from alfalfa, fig or primula that has been reported to give relatively high concentrations of mHep. Alfalfa is also referred to as Medicago sativa. Ficus carica (including, for example, cluster figs or winged figs) as well as Primula officinalis may be used.

Synthetic mHep
mHep may be obtained from “synthetic origin”. Synthetic mHep is commercially available in a highly pure state (Glycoteam GmbH (Hamburg, DE)). However, highly purified synthetic mHep has the same activity level as naturally derived raw materials of mHep such as avocado extract.

Microbe-derived mHep
mHep may be obtained from “microbe derived raw material”.

  One skilled in the art will understand how to determine the appropriate amount of mHep to be added to a given composition. Some non-limiting examples of factors to consider are: (i) the type of composition (eg, pet food composition or dietary supplement), (ii) the average of a particular type of composition from different animals Consumption, and (iii) conditions under which the manufacturing process and composition are adjusted. The compositions of the present invention are described in, for example, Waltham Book of Dog and Cat Nutrition, edited by ATB Edney, A.E. Rainbird, title "A Balanced Diet" p. 57-74, Pergamon Press Oxford, can be made according to any method appropriate in the art.

  In another aspect, the invention relates to a pet food composition comprising mHep for promoting or maintaining healthy body fat in a growing pet, wherein mHep is from about 0.0001% to about 10% of the composition. It is present in the composition by weight percent, from about 0.01% to about 5% by weight of the composition, or from about 0.1% to about 3% by weight of the composition. The term “healthy body fat” is intended to mean the average age-adjusted percentage of body fat that is considered healthy for a mammal. For example, when the mammal is a human, the “age adjusted body fat percentage recommended value” of the World Health Organization (WHO) can be referred to as a guideline. They have separate charts for men and women because women tend to have higher percentages for reproductive reasons.

Administration of Compositions The compositions of the present invention can be administered to mammals by various routes of administration. Such routes include, for example, oral, intranasal, intravenous, intramuscular, intragastric, transpyloric, subcutaneous, rectal and the like. In certain embodiments, the preferred route of administration is “oral” administration of the composition. “Oral” administration means that the mammal ingests the composition or that the human supplies the mammal with the composition of the invention, where the “human” supplying the composition is, for example, a pet owner, It may be a doctor, veterinarian or other health professional (eg pharmacist).

  Supply instructions for communicating and / or directing humans on how to use the composition and how to deliver to mammals include, for example, verbal or written instructions (eg, instructions from doctors, veterinarians, other health professionals); Radio, Internet or television media (e.g., advertisements); and / or packages (e.g., labels on the packages) attached to the composition. Alternatively, administration according to the present invention may be continuous or intermittent and will vary depending on the subject / patient. For example, consider the physiological condition of the subject / patient and whether the purpose of administration is treatment or prevention, and other factors known to those skilled in the art.

Method of using the composition According to the present invention, it has been found that mHep inhibits the differentiation process from adipose stem cells, especially mesenchymal stem cells (MSCs) to adipocytes, when cultured in the presence of a differentiation medium. After culturing, we discovered that mHep-administered adipose stem cells have the same overall gene expression pattern as undifferentiated cells that did not receive differentiation medium. It has also been discovered that mHep effectively suppresses the ability of differentiated adipose stem cells to accumulate lipids. These results indicate that mHep may be able to protect adipocytes from biological changes induced by excessive body fat accumulation through a reduction in the body's fat storage capacity.

  In one aspect of the invention, the invention relates to a method of treating or preventing overweight and obesity in a mammal, wherein the method comprises administering to the mammal a composition comprising an effective amount of mHep.

  In certain embodiments, the mammal is consuming more than the minimum caloric demand or is not on a dietary restriction plan.

  In another embodiment, the mammal is a human (eg, female, male). When referring to humans, the terms “overweight” and “obesity” are used to identify weight / body obesity status based on the body mass index (BMI) of a human subject. Table 2 below shows the range of BMI for each physical condition according to the guidelines given by the US CDC. BMI is determined by measuring the weight of a subject and dividing it by height.

In another embodiment, the mammal is:
a) Unfertile fertile pups, unfertile kittens, overweight or obese puppies, overweight or obese kittens, puppies that have undergone ovariectomy or castration surgery, and kittens that have undergone ovariectomy or castration surgery A growing pet selected from the group consisting of;
b) Adult dogs with no fertility, adult cats with no fertility, overweight or obese adult dogs, overweight or obese adult cats, adult dogs undergoing ovariectomy or castration surgery, ovariectomy or castration surgery An adult pet selected from the group consisting of an adult cat who has undergone; or c) an old fertile dog with no fertility, an old cat with no fertility, an overweight or obese old dog, an overweight or obese old cat, An elderly dog selected from the group consisting of an old dog that has undergone ovariectomy or castration surgery, and an old cat that has undergone ovariectomy or castration surgery;
A pet that is more selected.

  When the mammal is a pet, the terms “overweight” and “obesity” are reproduced by cats developed by “IAMS” Greg Sunvold (1998), as reproduced in FIGS. 1A (dogs) and 1B (cats). Refers to the state of body weight / body obesity based on the assessment of the animal's body using a body condition chart (BCS) to assess obesity in dogs. The chart shows five different weight / obesity status conditions: (1) lean, (2) underweight, (3) ideal, (4) overweight, and (5) obesity to facilitate evaluation. Each type of physical feature is defined and given. The benefit of the chart method is that it gives some degree of uniformity to the evaluation.

  Furthermore, since mHep has been observed to have only a limited effect on adipocytes that have already differentiated and accumulated lipids, the extent of adipocyte response is determined by the adipocyte differentiation stage. It was found that this also depends on the timing of mHep administration. Thus, the benefits of mHep on adipocyte function depend on early mHep administration prior to the onset of adipocyte differentiation. Once adipose stem cells have differentiated into adipocytes, it is difficult to remove them. Thus, the purpose of early administration of mHep to mammals is to inhibit the differentiation process and limit the body's retention of adipocytes.

  In another embodiment, the mammal is a growing pet, such as a kitten or puppy. The kitten may be a domestic cat that is 3 years old or younger, 2 years old or younger, or 1 year old or younger. The puppy may be a breeding dog that is 3 years old or younger, 2 years old or younger, or 1 year old or younger. Preferably, growing pets require such treatment because the animal is overweight or obese, or the method is a prophylaxis to prevent the mammal from becoming overweight or obese. Non-limiting examples of growing pets in need of such treatment include overweight puppies, obese puppies, overweight kittens, or obese kittens.

  Because compositions containing mHep are administered to growing pets before they are fully developed to normal adult weight, it is not possible to completely control weight gain and is healthy not. The method of the present invention allows for substantial weight gain of body mass in the body without fat, while at the same time treating or preventing weight gain due to excessive fat accumulation. Thus, for growing pets, overweight or obesity that is the subject of this new method is characterized by weight gain substantially due to excessive fat accumulation in adipose tissue. The composition of the present invention has a slight effect on body mass of fat-free body.

  In another embodiment, the growing pet may be fertile or may preferably have undergone oophorectomy or castration surgery. It may be after weaning and before reaching sexual maturity. Genital removal results in significantly reduced levels of endogenous sex hormones (eg, estrogen). As a result, weight gain is common in mammals after ovariectomy or castration surgery. Thus, the methods of the present invention may benefit growing pets undergoing ovariectomy or castration surgery.

  In another embodiment, the method is for preventing overweight and obesity in a mammal of the body characterized as lean, underweight or ideal. From the mechanism of action it is clear that mHep is unable to treat an animal if the mammal is obese with significant body fat stores. However, for adult / aged pets, mHep may be advantageous to prevent overweight and obesity if they do not generate significant amounts of body fat. In this scenario, MH is otherwise associated with overweight and obesity in adult / aged pets with no fat, regardless of whether they are undamaged or undergoing castration surgery. It is thought to contribute to the prevention / minimization of “spread” or “age related body fat gain”.

  In this embodiment, mammals considered suitable for this prophylactic method are from about 0.1% to about 20%, or from about 0.5% to about 15%, or from about 1% to about 10% of total body weight. With a percentage of total body fat. Alternatively, another method of identifying whether a mammal is overweight or obese is that the mammal is slim, underweight if measured based on the following points: (i) the physical condition chart described herein Or a physical condition characterized as ideal; or (ii) 1 to 3 bodies based on a scale of 1 to 5 when measuring BCS according to the physical condition score test disclosed herein By checking if it has a state score (BCS).

  For example, FIGS. 1A and 1B show physical condition charts for dogs and cats (available from “IAMS” (1998)). The physical condition chart shows five types of physical conditions (slimming, underweight, ideal, overweight and obesity), such as non-specialists (eg pet owners) and professionals (eg veterinarians and veterinarians) It is shown together with body standards that can be easily seen and measured by the person.

  The BCS method is the most commonly used method for estimating obesity in pets. Under the BCS method, a physical condition score may be assigned by using physical measurements, visual observation and palpation. The body condition score is a semi-quantitative evaluation method of body fat, and every 0.25 points, the following scale of 1 to 5 is used: 1 = recumbent, 2 = slimming, 3 = average, 4 = thick and 5 = Obesity is used. In another embodiment, the method of administering to a mammal a composition comprising an effective amount of mHep inhibits or reduces the differentiation process from adipose stem cells to adipocytes in the mammal. As used herein, an “effective amount” of mHep treats or prevents overweight and obesity when administered to mammals, preferably humans or domestic animals, such as pets or companion animals (eg, cats, dogs). Refers to the amount of mHep in the composition of the invention sufficient. This “effective amount” of mHep, a component of the composition of the present invention, will vary depending on the condition and severity, the mode / mode of administration, the age of the mammal to be treated and its overall health, It can be routinely determined by one of ordinary skill in the art that is aware of the present disclosure.

  The dosage of mHep depends on the form in which mHep is delivered to the mammal. The dose varies depending on the size and condition of the pet to which mHep is to be administered. A dose in the range of about 0.0001 or about 0.001 g / kg to about 1 g / kg may be advantageous in some embodiments. As used herein, when a mg / kg dose is used, mg refers to the amount of mHep, and kg is preferably kilograms of the mammal's body weight when the mammal is a human or a pet, such as a cat or dog. Point to. In one embodiment, the dose of ingredients given to the pet per day is from about 0.1, 0.5, 1, 2, or 5 mg / kg to about 15, 20, 50, 100, 150, or 200 mg / kg, and Any combination of these ranges may be used, where “mg” refers to the amount of mHep and “kg” refers to kilograms of mammalian body weight. In one embodiment, the daily dose of the pet is about 0.1 mg / kg to about 50 mg / kg, about 1 mg / kg to about 20 mg / kg, 1 mg / kg to about 15 mg / kg, about 2 mg / kg to about 10 mg. / Kg, or about 2 mg / kg to about 5 mg / kg, or about 2 mg / kg. In certain embodiments, these amounts are all less than about 5%, or less than about 2%, or from about 0.0001% to about 0.5%, or about 0.1% by weight of the composition. To about 10% by weight, or about 5% by weight of mHep. In certain embodiments, mHep is from about 0.0001% to about 10%, or from about 0.01% to about 5%, or from about 0.1% to about 3% by weight of the composition. Present in the composition in a range. All ranges between these are also included. The amount of mHep may be determined by one skilled in the art based on various factors such as the form of the composition. For example, if the composition is a pet food composition, it is selected from a dry composition, a semi-moist composition, a water-containing composition, or a supplement, or any other form or mixture thereof. One skilled in the art can utilize the preferred dosage regimen to determine the optimal amount of mHep within a given composition.

  In another embodiment, administration of mHEp inhibits or reduces the differentiation process from adipose stem cells to adipocytes, resulting in a lower amount of adipocytes, whereby the mammal's fat storage capacity is compared to an untreated mammal. About 5%, about 10%, or about 20% or more.

  In another embodiment, the invention relates to a method for promoting or maintaining a healthy weight in a mammal, the method comprising an effective amount of a composition comprising mHep to prevent or reduce excess body fat in a mammal. Administering the composition to the mammal. “Excess body fat” may be any amount that makes it appropriate for a mammal to be considered overweight or obese.

  In yet another aspect, the invention relates to a method for preventing or ameliorating overweight and obesity in a mammal comprising providing the mammal with a composition comprising mHep present in the composition. mHep is present from about 0.0001% to about 10% by weight of the composition, from about 0.01% to about 5% by weight of the composition, or from about 0.1% to about 3% by weight of the composition. . The composition is selected from the group consisting of pet foods, supplements and liquids, where the supplements or liquids can be ingested or added to the pet food and the mammal is an adult pet or an aged pet.

  In yet another aspect, the invention relates to a method for preventing or ameliorating overweight and obesity in a mammal comprising providing the mammal with a composition comprising mHep. mHep is present from about 0.0001% to about 10% by weight of the composition, from about 0.01% to about 5% by weight of the composition, or from about 0.1% to about 3% by weight of the composition. Wherein the composition is selected from the group consisting of pet foods, supplements and liquids, where the supplements or liquids can be ingested or added to the pet food and the mammal is an adult pet or an aged pet.

  In yet another aspect, the present invention provides a composition comprising a daily dose of mHep from 1 mg / kg to about 50 mg / kg, or from 1 mg / kg to about 15 mg / kg, or from 1 mg / kg to about 5 mg / kg. It relates to a method for extending the lifespan of a mammal comprising the step of administering to a mammal. For example, mammals that have been exposed to mHep for a long time by initiating treatment soon after birth are expected to benefit more in terms of extended lifespan. In certain embodiments, administration begins with the mammal at about 1 month or less, about 6 months or less, about 1 year or less, about 2 years or less, or about 3 years or less. In certain embodiments, the reduction in calories consumed by the mammal is at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, or at least about 50%. In another embodiment, the lifetime is extended by about 10% or more, about 15% or more, about 20% or more, about 25%, about 30% or more, or about 35% or more.

In another embodiment, in a method for extending life,
(I) administration of mHep begins when the mammal is about 1 month old with a life extension of about 30% or more;
(Ii) administration of mHep begins when the mammal is about 6 months of age with a life extension of about 25% or greater;
(Iii) administration of mHep begins when the mammal is about 1 year old and has a life extension of about 20% or more;
(Iv) administration of mHep begins when the mammal is about 2 years old with a life extension of about 15% or greater; and
(V) Administration of mHep begins when the mammal is about 3 years old and has a life extension of about 10% or more.

Combination Therapy A composition comprising an effective amount of mHep of the present invention, or an effective amount of mHep is useful in combination with one or more other therapeutic agents or any combination thereof in the treatment of overweight or obesity. You can go.

Package The present invention also includes a composition comprising an effective amount of mHep as described above, preferably in the form of a package, with a composition to a feline companion animal together with a feeding manual with instructions on how to administer it. Of commercial products. Any standard package suitable for delivery and sale of the compositions disclosed herein can be used. The package also describes specific written benefits relating to the treatment or prevention of overweight or obesity in mammals, preferably when the mammal is a pet, more preferably when the pet is a growing pet, such as a kitten or puppy. Can also be included.

  The benefit statement can also relate to health benefits derived from such treatment or prevention, such as weight loss, healthy weight, healthy body fat, and extended lifespan.

  The following examples are presented to illustrate embodiments of the invention and are not intended to limit the scope in any manner.

Example 1-Preparation of an Avocado Extract An avocado extract containing an enhanced amount of mannoheptulose was prepared according to the following optional process and utilized in the compositions of embodiments of the present invention.

  All avocado fruits (about 900 kg) were prepared. The fruit was divided, and the nucleus was completely or partially removed to obtain an avocado bisector with approximately 225 kg of nucleus removed. Raw avocado was filled into a grinder, and further charged with water (about 3000 kg) and CELLUBBRIX (distributor: Novozymes A / S) (about 1 liter) while stirring to some extent. The mixture was further stirred and simultaneously heated to about 66 ° C. After filling, more CELLUBRICX (about 1 L) was added and the entire mixture was held in CELLUBRICX with stirring for about 12 hours at a controlled pH of about 5.5. The temperature was then further increased to about 80 ° C. and then held for at least about 2 hours. The resulting digested plant mixture was then filtered at 80 ° C. to obtain a carbohydrate extract as a filtrate. The carbohydrate extract was then evaporated in a simplified recirculation system at 80 ° C. under vacuum to obtain a carbohydrate extract having a solids content of about 10% to about 20% and a pH of about 5.5. The extract was then further concentrated using a refractance window dryer to obtain about 100 kg of extract as a crystalline or powdered substance (with a yield of about 11% carbohydrate extract based on the total avocado fruit starting mass). And this is analyzed to be a mHep yield of about 0.25% to about 4.5% based on the starting mass of all avocado fruit). It should be noted that the amount of mHep present in the avocado varies depending on the particular plant line and fruit ripeness. Extracts may be used in the compositions of embodiments of the present invention.

Example 2-Effect of mHep on mesenchymal stem cell (MSC) differentiation
Test 1 —This test describes an in vitro assay to test the effect of mHep on terminal differentiation from mesenchymal stem cells (MSCs) (ie, adipose stem cells) to functional adipocytes. MSC differentiation from preadipocytes to functional adipocytes by culturing MSC (C57BL / 6) (Gibco) in adipocyte differentiation medium (Invitrogen) at 37 ° C. in the presence of palmitate at 5% CO _2. Induced. MSC control plates were cultured in ADP-free basal medium (BP) as a negative control (ie reflecting undifferentiated MSCs).

  The following samples: (i) 3 concentrations of mHep at 1.16 nM, 11 mM and 22 mM; (ii) whole fruit avocado extract supplemented with 0.2% of 25% fortified mHep; and (iii) 50 μM resveratrol. Their effects on adipocyte differentiation were evaluated by addition to ADP-containing MSC cultures. Endpoint measurements include (i) oil red staining as a measure of accumulated fat; (ii) visual inspection of adipocytes; and (iii) ATP assay to measure cell viability. The sensitivity of the assay allows for testing of millimolar levels of mHep for adipocyte differentiation.

Result 1
According to the results, the addition of palmitate into the differentiation cocktail increases lipid accumulation beyond the basal medium. MSC cultures with mHep (11 mM and 22 mM) or whole fruit avocado extract (0.2%) present in the medium regress lipid accumulation to near basal levels. These results suggest that fat cell differentiation and the ability of differentiated adipocytes to accumulate lipids are suppressed based on oil red staining (FIG. 2). The results are also supported by the lower mHep dose (1.16 mM), or the heat-inactivated raw material of whole fruit avocado extract (0.2%), which reduces the effect of preventing fat cell differentiation and fat accumulation.

Test 2 -In this test, the effect of delayed mHep administration on MSC differentiation is tested. 22 mM mHep was added to the MSC cultures on days 0, 4 and 7 and endpoints were measured by oil red staining as a measure of accumulated fat. Controls were cultured as negative controls in ADP-free basal medium (BP) (ie reflecting undifferentiated MSCs).

Result 2
When mHep was added after differentiation and the fat cells were accumulating lipids, the inhibitory effect of mHep was observed to disappear. The table shown below shows the effect on MSC differentiation due to delayed addition of mHep (22 mM) until day 4 and day 7. The results show the same oil red staining results as MSC-induced control cells grown in differentiation medium in the absence of MH. On the other hand, the addition of MH on day 0 caused the same inhibitory action on lipid accumulation as described above. These results suggest that MH prevents lipid accumulation by directly affecting the differentiation process of adipocytes. Once adipocytes have differentiated and accumulated lipids, MH is considered to have no effect on them. That is, any advantage of MH on adipocyte function depends on early MH administration prior to the onset of adipocyte differentiation.

  All maximum numerical limits given throughout this specification are such that all lower numerical limits are expressly set forth herein, such low numerical limits. Should be understood to encompass. All minimum numerical limits given throughout this specification include such high numerical limits, as all higher numerical limits are expressly set forth herein. To do. All numerical ranges given throughout this specification are such that all narrower numerical ranges that fall within such broader numerical ranges are expressly set forth herein. , Including such narrower numerical ranges.

  All parts, ratios and percentages set forth in the specification, examples and claims are by weight unless otherwise indicated, and all numerical limits are used with the usual accuracy possible for those skilled in the art. All documents cited in the detailed description of the invention are hereby incorporated by reference in the relevant part; any citation of any document shall be construed as an admission that it is prior art with respect to the present invention. Don't be.

  The dimensions and values disclosed herein are not to be understood as being strictly limited to the exact numerical values shown. Rather, unless otherwise specified, each such dimension is intended to mean both the recited value and a functionally equivalent range surrounding that value. For example, a dimension disclosed as “40 mm” is intended to mean “about 40 mm”.

  All documents cited herein, including any cross-references or related patents or applications, are hereby incorporated by reference in their entirety unless expressly excluded or specifically stated. The citation of any document is prior art with respect to any invention disclosed or claimed herein, or teaches any such invention, alone or in combination with any other reference. Does not permit the disclosure or disclosure. Furthermore, any meaning or definition of a term in this document shall be assigned to that term in this document as long as it is inconsistent with any meaning or definition of the same term in the document incorporated herein by reference. Or definition takes precedence.

  While particular embodiments of the present invention have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. Accordingly, all such changes and modifications within the scope of this invention are intended to be covered by the appended claims.

Claims (15)

  A method of treating or preventing overweight and obesity in a mammal, the method comprising administering to the mammal a composition comprising an effective amount of mannoheptulose (mHep). Said method has the following characteristics:
i. A physical condition characterized as lean, underweight or ideal as measured based on the physical condition chart disclosed herein; or
ii. A body condition score (BCS) of 1 to 3 based on a scale of 1 to 5;
2. The method of claim 1, wherein the method is for preventing overweight and obesity in a mammal having the following. The mammal is:
a) a growing pet selected from the group consisting of undamaged growing pets, overweight or obese growing pets and growing pets that have undergone ovariectomy or castration;
b) an adult pet selected from the group consisting of an undamaged adult pet, an overweight or obese adult pet and an adult pet that has undergone ovariectomy or castration;
c) an aged pet selected from the group consisting of an undamaged aged pet, an overweight or obese aged pet or an aged pet that has undergone ovariectomy or castration;
The method of claim 1, wherein a) the adult pet is selected from the group consisting of an intact fertile dog, an unfertile adult cat, an adult dog that has undergone ovariectomy or castration surgery, an adult cat that has undergone ovariectomy or castration surgery; Or
b) the old pet is selected from the group consisting of an old fertile dog, an old fertile cat, an old dog that has undergone ovariectomy or castration surgery, and an old cat that has undergone ovariectomy or castration surgery;
Wherein the percentage of total fat of the adult or old pet is from about 0.1% to about 20%, or from about 0.5% to about 15%, or from about 1% to about 10% of the total body weight. Item 4. The method according to Item 3.   4. The mammal being treated for overweight and obesity is a growing pet, wherein overweight or obesity is characterized by weight gain substantially due to excessive fat accumulation in adipose tissue. Method.   6. The method according to any one of claims 1 to 5, wherein administration of the composition comprising an effective amount of mHep to the mammal suppresses or reduces the differentiation process from adipose stem cells to adipocytes in the mammal.   Inhibition or reduction of the differentiation process from adipose stem cells to adipocytes results in low adipocytes, so that the body's fat storage capacity is at least about 5%, about 10%, compared to untreated mammals, 7. The method of claim 6, wherein the method is reduced by at least about 20%.   Providing said mammal with a composition comprising an effective amount of mHep, said effective amount being from about 0.1 mg / kg to about 50 mg / kg, or from about 1.0 mg / kg to about 20 mg / kg of mHep. And the composition is selected from the group consisting of pet foods, supplements and liquids, wherein the supplements or liquids can be ingested separately or added to the pet food. The method of claim 6. The mHep is:
a) Naturally derived mHep raw material;
b) mHep raw material derived from synthesis;
c) mHep raw material derived from microorganisms;
d) a combination of a) and b);
e) a combination of a) and c);
f) a combination of b) and c);
g) a combination of a), b) and c);
9. The method of any one of claims 1 to 8, wherein the method is derived from.   The natural source of mHep is avocado, avocado extract, avocado powder, avocado concentrate, avocado juice, alfalfa, alfalfa extract, alfalfa powder, alfalfa concentrate, alfalfa juice, fig, fig extract, fig powder, fig concentrate, fig 10. The method of claim 9, selected from the group consisting of juice, primula, primula extract, primula powder, primula concentrate, primula juice, and mixtures thereof.   Compositions wherein the mHep is from about 0.0001% to about 10% by weight of the composition, from about 0.01% to about 5% by weight of the composition, or from about 0.1% to about 3% by weight of the composition The method of claim 1, wherein the method is present in an object. The composition has the following fat content in the composition:
a) at least about 10% by weight of the composition;
b) at least about 15% by weight of the composition;
c) at least about 25% by weight of the composition;
d) at least about 35% by weight of the composition; or
e) at least about 40% by weight of the composition;
The method of claim 1, wherein the method is a high fat food product.   A method for promoting or maintaining a healthy body weight in a mammal, the composition comprising an effective amount of mannoheptulose (mHep) in the mammal to prevent or reduce excess body fat in the mammal Administering a step of administering.   A pet food composition comprising mannoheptulose (mHep) for promoting or maintaining healthy body fat in a growing pet, wherein the mHep is from about 0.0001% to about 10% by weight of the composition, A pet food composition present in the composition from about 0.01% to about 5% by weight of the composition, or from about 0.1% to about 3% by weight of the composition. The composition has the following fat content in the composition:
a) at least about 10% by weight of the composition;
b) at least about 15% by weight of the composition;
c) at least about 25% by weight of the composition;
d) at least about 35% by weight of the composition; or
e) at least about 40% by weight of the composition;
The composition according to claim 14, which is a high-fat food having