EP3709818A1 - Procédés de mesure de la production équivalente de réduction par des tissus pour déterminer des taux métaboliques et procédés d'utilisation - Google Patents

Procédés de mesure de la production équivalente de réduction par des tissus pour déterminer des taux métaboliques et procédés d'utilisation

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Publication number
EP3709818A1
EP3709818A1 EP18878766.7A EP18878766A EP3709818A1 EP 3709818 A1 EP3709818 A1 EP 3709818A1 EP 18878766 A EP18878766 A EP 18878766A EP 3709818 A1 EP3709818 A1 EP 3709818A1
Authority
EP
European Patent Office
Prior art keywords
animal
metabolic rate
production
reducing equivalent
animals
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP18878766.7A
Other languages
German (de)
English (en)
Other versions
EP3709818A4 (fr
Inventor
Benjamin J. RENQUIST
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Arizona
Original Assignee
University of Arizona
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by University of Arizona filed Critical University of Arizona
Publication of EP3709818A1 publication Critical patent/EP3709818A1/fr
Publication of EP3709818A4 publication Critical patent/EP3709818A4/fr
Pending legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/10—Feeding-stuffs specially adapted for particular animals for ruminants
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/008—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions for determining co-enzymes or co-factors, e.g. NAD, ATP
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5082—Supracellular entities, e.g. tissue, organisms
    • G01N33/5088—Supracellular entities, e.g. tissue, organisms of vertebrates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/52—Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06Q—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR ADMINISTRATIVE, COMMERCIAL, FINANCIAL, MANAGERIAL OR SUPERVISORY PURPOSES; SYSTEMS OR METHODS SPECIALLY ADAPTED FOR ADMINISTRATIVE, COMMERCIAL, FINANCIAL, MANAGERIAL OR SUPERVISORY PURPOSES, NOT OTHERWISE PROVIDED FOR
    • G06Q50/00—Information and communication technology [ICT] specially adapted for implementation of business processes of specific business sectors, e.g. utilities or tourism
    • G06Q50/02—Agriculture; Fishing; Forestry; Mining

Definitions

  • the present invention relates to the use of measuring reducing equivalents, such as NADH, FADH 2 , NADP(H), and/or Coenzyme Q, to measure tissue metabolic rate in animals and humans.
  • the methods of measuring reducing equivalents provide a high throughput means of determining metabolic rates of animals or humans.
  • the methods may be used for a variety of purposes, for example assessing feed efficiency, assessing productivity of animals, determining a likelihood of developing obesity, sorting animals, etc.
  • Basal metabolic rate may be estimated by housing animals in metabolic chambers, but the use of metabolic chambers is difficult due to practical and economic challenges.
  • neither of these measures have the sensitivity associated with the accumulation of signal noted with this invention, and both are subject to exchange of gases between the media and the air.
  • the technique described herein was previously used to assess ceil viability, not metabolic rate. Thus, it was surprising to discover that measuring reducing equivalents in tissues of an animal (or human) could be used as a proxy for measuring the metabolic rate of the animal (or human). An additional leap was made when it was discovered that tissue metabolic rate could be applied to assess an individual’s feed efficiency or a tissue’s production potential.
  • the methods of the present invention feature measuring reducing equivalents (e.g., NADH, FADH 2 , NADP(H), Coenzyme Q, etc.), which are used to determine the metabolic rate of the animal or human (e.g., tissue-specific metabolic rate).
  • the present invention provides a high throughput means of determining metabolic rate of an animal or human.
  • the present invention also features the use of said methods, e.g., the methods for measuring metabolic rates using reducing equivalent measurements.
  • the methods herein may be used to:
  • high producing animals e.g., high milk production, high egg production, meat production, or any other appropriate animal product
  • the technology of the present invention is advantageous because it provides a fast, high-throughput, scalable and easy means of assessing metabolic rate of tissues (via ceil viability assays, e.g., measuring reducing equivalents), while allowing the user to associate that metabolic rate to parameters such as feed efficiency and tissue-specific production formation.
  • ceil viability assays e.g., measuring reducing equivalents
  • the technology of the present invention is advantageous because it provides a fast, high-throughput, scalable and easy means of assessing metabolic rate of tissues (via ceil viability assays, e.g., measuring reducing equivalents), while allowing the user to associate that metabolic rate to parameters such as feed efficiency and tissue-specific production formation.
  • ceil viability assays e.g., measuring reducing equivalents
  • the present invention features methods of measuring reducing equivalents (e.g., NADH, FADH 2 , Coenzyme Q, etc.) in a tissue of an animal (or human) to determine the metabolic rate of the animal (or human) (or a tissue-specific metabolic rate).
  • the present invention is not limited to any particular method for measuring reducing equivalents.
  • the present invention is not limited to the use of resazurin, MTT, or any other particular reducing equivalent indicator.
  • measuring reducing equivalents may feature measuring NADH production.
  • measuring reducing equivalents may feature measuring FADH 2 production.
  • measuring reducing equivalents may feature measuring Coenzyme Q.
  • measuring reducing equivalents may feature measuring a combination of NADH, FADH 2 , NADP(H), or Coenzyme Q.
  • the term“animal” may refer to any appropriate animal or human, e.g., cattle (e.g., dairy cattle, beef cattle), goats, sheep, swine, mice, dogs, cats, humans, non-human primates, chickens, fish, moliusks, etc.
  • cattle e.g., dairy cattle, beef cattle
  • goats, sheep, swine mice
  • dogs, cats humans
  • non-human primates chickens
  • fish moliusks
  • the methods of the present invention may be used to determine a likelihood of obesity.
  • the methods and systems of the present invention are not limited to the animals disclosed herein.
  • tissue may refer to any appropriate tissue of the animal or human, e.g., skeletal muscle, mammary tissue, brown adipose tissue, white adipose tissue, liver, kidney, fin, etc.
  • the methods and systems of the present invention are not limited to the tissues disclosed herein.
  • a lower tissue-specific metabolic rate can be indicative of a lower whole animal basal metabolic rate (energy expended to maintain proper tissue function without a change in tissue mass) if that tissue mass is large relative to whole body mass (e.g. skeletal muscle).
  • a lower basal metabolic rate allows for less of the dietary energy to go toward body maintenance energy requirements and more to go toward growth or product (e.g., milk, eggs, meat, etc.) formation.
  • a low skeletal muscle metabolic rate in slow/non- growing adult animals is indicative of the potential for good feed efficiency (product mass/feed mass), and a high potential for product (e.g., milk, meat) production, etc.
  • the present invention also features the use of the methods of measuring reducing equivalents for determining metabolic rates of animals (or humans).
  • the present invention provides methods of identifying animals with a particular feed efficiency, e.g., a high feed efficiency.
  • feed efficiency refers to the amount of weight gained per unit of feed or product produced per unit feed.
  • the present invention also features methods of stratifying animals based on feed efficiency.
  • the present invention also features method of selection (e.g., methods of grouping, sequestering, etc.) of animals with a particular feed efficiency, e.g., a high feed efficiency.
  • feed efficiency determined by the methods herein may be used to calculate an expected progeny difference.
  • the aforementioned methods may comprise determining the reducing equivalent production (e.g., an amount, a change in, etc.) in a tissue sample (e.g., skeletal muscle tissue sample) from the animal, wherein the reducing equivalent production (e.g., an amount, a change in, etc.) in the tissue sample is inversely related to feed efficiency.
  • determining the reducing equivalent production e.g., an amount, a change in, etc.
  • a tissue sample e.g., skeletal muscle tissue sample
  • the animal from which the skeletal muscle tissue sample was obtained has a high feed efficiency compared to animals having a reducing equivalent production (e.g., an amount, a change in, etc.) above the predetermined threshold.
  • Determining the reducing equivalent production (e.g., an amount, a change in, etc.) in the tissue sample may comprise introducing a reducing equivalent indicator to the tissue sample and measuring an amount of or a change in reducing equivalent indicator (which is indicative of metabolic activity).
  • the predetermined threshold may be an average of reducing equivalent production for a breed, herd, or species of the animal.
  • the predetermined threshold may be determined by the user, e.g., based on a desired stringency of selection for feed efficiency.
  • the predetermined threshold may be a percentile level (e.g., 5 th percentile, 10 th percentile, 25 th percentile, 50 th percentile, etc.).
  • the predetermined threshold may be determined using a cohort of animals with a known reducing equivalent production (e.g., an amount, a change in, etc.) and known feed efficiencies.
  • the predetermined threshold may stratify animals by feed efficiency.
  • the reducing equivalent is NADH. In some embodiments, the reducing equivalent is NADP(H). In some embodiments, the reducing equivalent is FADH 2 . In some embodiments, the reducing equivalent is Coenzyme Q. In some embodiments, the reducing equivalent is NADH or FADH 2 . In some embodiments, the reducing equivalent is NADH or Coenzyme Q. In some embodiments, the reducing equivalent is FADH 2 or Coenzyme Q. In some embodiments, the reducing equivalent is NADH or NADP(H). In some embodiments, the reducing equivalent is NADP(H) or CoEnzyme Q. In some embodiments, the reducing equivalent is NADP(H) or FADH 2 .
  • the reducing equivalent is one or more of: NADH, FADH 2 , NADP(H), and Coenzyme Q. In some embodiments, the reducing equivalent is NADH, FADH 2 , or Coenzyme Q. In some embodiments, the reducing equivalent is NADH, FADH 2 , NADP(H), or Coenzyme Q.
  • the method may further comprise using the animal identified as having high feed efficiency for breeding.
  • the method may further comprise using the animal identified as having high feed efficiency for production of an animal product (e.g., milk, meat, etc.).
  • an animal product e.g., milk, meat, etc.
  • the present invention also provides methods of identifying animals with a particular milk production, e.g., high milk production.
  • the present invention also features methods of stratifying animals based on milk production.
  • the present invention also features method of selection (e.g., methods of grouping, sequestering, etc.) of animals with a particular milk production, e.g., a high milk production.
  • the aforementioned methods may comprise determining reducing equivalent production (e.g., an amount, a change in, etc.) in a mammary tissue sample from the animal, wherein the reducing equivalent production (e.g., an amount, a change in, etc.) in the mammary tissue sample is directly related to potential for milk production.
  • reducing equivalent production e.g., an amount, a change in, etc.
  • the animal from which the mammary tissue sample was obtained has a high milk production potential compared to animals having a reducing equivalent production (e.g., an amount, a change in, etc.) below the predetermined threshold.
  • Determining the reducing equivalent production in the tissue sample may comprise introducing a reducing equivalent indicator to the tissue sample and measuring an amount of or a change in reducing equivalent indicator (which is indicative of metabolic activity).
  • the predetermined threshold may be an average of reducing equivalent production for a breed, herd, or species of the animal.
  • the predetermined threshold may be determined by the user, e.g., based on a desired stringency of selection for milk production potential.
  • the predetermined threshold may be a percentile level (e.g., 5 th percentile, 10 th percentile, 25 ni percentile, 50 th percentile, etc.).
  • the predetermined threshold may be determined using a cohort of animals with a known reducing equivalent production (e.g., an amount, a change in, etc.) and known milk production.
  • the predetermined threshold may stratify animals by milk production potential.
  • the reducing equivalent is NADH. In some embodiments, the reducing equivalent is NADP(H). In some embodiments, the reducing equivalent is FADH 2 . In some embodiments, the reducing equivalent is Coenzyme Q. In some embodiments, the reducing equivalent is NADH or FADH 2 . In some embodiments, the reducing equivalent is NADH or Coenzyme Q. In some embodiments, the reducing equivalent is FADH 2 or Coenzyme Q. In some embodiments, the reducing equivalent is NADH or NADP(H). In some embodiments, the reducing equivalent is NADP(H) or CoEnzyme Q. In some embodiments, the reducing equivalent is NADP(H) or FADH 2 .
  • the reducing equivalent is one or more of: NADH, FADH 2 , NADP(H), and Coenzyme Q.
  • the reducing equivalent Is NADH, FADH 2 , or Coenzyme Q.
  • the reducing equivalent is NADH, FADH 2 , NADP(H), or Coenzyme Q.
  • the method may further comprise using the animal identified as having high milk production for breeding.
  • the method may further comprise using the animal identified as having high milk production for production of milk.
  • the present invention also features methods of calculating a feed efficiency breeding value for an animal.
  • the method comprises determining a feed efficiency based on metabolic rate of a tissue sample from the animal, e g , as described herein, e.g., wherein metabolic rate is determined by determining reducing equivalent production (e.g., an amount, a change in, etc.); and assigning an estimated expected progeny difference from the breed average based on the metabolic rate of the tissue sample.
  • the estimated breeding value indicates the genetics for feed efficiency of the potential brood stock.
  • the method further comprises combining estimated feed efficiency with one or more additional estimated breeding values, e.g., ribeye area, intramuscular fat, fat depth, birth weight, weaning weight, and carcass yield.
  • the present invention also features methods of favoring or skewing a genetic makeup of an animal population (e.g., a newborn animal population) towards having a high feed efficiency.
  • the method comprises determining a metabolic rate of a tissue sample (e.g., skeletal muscle tissue) from the animals (as described herein).
  • the method further comprises selecting the animals with the best feed efficiency for breeding a newborn animal population with a particular predicted feed efficiency.
  • the present invention also features methods of favoring or skewing a genetic makeup of an animal population (e.g., a newborn animal population) towards having high milk production.
  • the method comprises determining a metabolic rate of a tissue sample (e.g , mammary tissue) from the animals (as described herein).
  • the method further comprises selecting the animals with the best milk production for breeding a newborn animal population with a particular predicted milk production.
  • the present invention also features methods for detecting an effect of a drug, dietary supplement, diet, or other composition on feed efficiency of an animal.
  • the method comprises determining a baseline tissue-specific metabolic rate for the animal by measuring reducing equivalent production (e.g., an amount, a change in, etc.) in a first tissue sample (e.g., skeletal muscle) from the animal; administering the drug, dietary suppiement, diet, or other composition to the animal; then determining the reducing equivalent production in a second tissue sample of the tissue of the animal (a second tissue-specific metabolic rate).
  • reducing equivalent production e.g., an amount, a change in, etc.
  • the drug, dietary suppiement, diet, or other composition does not affect feed efficiency of the animal. In some embodiments, if the second tissue-specific metabolic rate is less than the baseline tissue-specific metabolic then the drug, dietary supplement, diet, or other composition has a positive effect on feed efficiency of the animal. In some embodiments, if the second tissue-specific metabolic rate is greater than the baseline tissue-specific metabolic then the drug, dietary supplement, diet, or other composition has a negative effect on feed efficiency of the animal.
  • the method comprises administering the drug, dietary supplement, diet, or composition to the animal; and determining a metabolic rate for the animal by determining reducing equivalent production (e.g., an amount, a change in, etc.) in a tissue (e.g., skeletal muscle) of the animal.
  • reducing equivalent production e.g., an amount, a change in, etc.
  • a tissue e.g., skeletal muscle
  • the control metabolic rate being a metabolic rate of one or a group animals not administered the drug, dietary supplement, diet, or other composition
  • the drug, dietary supplement, diet, or other composition does not affect feed efficiency of the animal.
  • the metabolic rate of the animal is less than a control metabolic rate, the control metabolic rate being a metabolic rate of one or a group animals not administered the drug, dietary supplement, diet, or other composition, then the drug, dietary supplement, diet, or other composition has a positive affect on feed efficiency of the animal.
  • the metabolic rate of the animal is greater than a control metabolic rate, the control metabolic rate being a metabolic rate of one or a group animals not administered the drug, dietary supplement, diet, or other composition, then the drug, dietary supplement, diet, or other composition has a negative effect on feed efficiency of the animal.
  • the present invention also features methods of detecting an effect of a drug, dietary supplement, diet, or other composition on milk production of an animal.
  • the method comprises determining a baseline tissue-specific metabolic rate for the animal by measuring reducing equivalent production (e.g., an amount, a change in, etc.)in a first tissue sample of a mammary tissue of the animal; administering the drug, dietary supplement, diet, or other composition to the animal; and determining a second tissue-specific metabolic rate for the animal by measuring reducing equivalent production (e.g., an amount, a change in, etc.) in a second tissue sample of the mammary tissue of the animal.
  • reducing equivalent production e.g., an amount, a change in, etc.
  • the drug, dietary supplement, diet, or other composition does not affect milk production of the animal. In some embodiments, if the second tissue-specific metabolic rate is less than the baseline tissue-specific metabolic then the drug, dietary supplement, diet, or other composition has a negative effect on milk production of the animal. In some embodiments, if the second tissue-specific metabolic rate is greater than the baseline tissue-specific metabolic then the drug, dietary supplement, diet, or other composition has a positive effect on milk production of the animal.
  • the method comprises administering the drug, dietary supplement, diet, or composition to the animal; and determining a tissue-specific metabolic rate for the animal by determining reducing equivalent production (e.g., an amount, a change in, etc.) in a mammary tissue of the animal.
  • reducing equivalent production e.g., an amount, a change in, etc.
  • the control tissue-specific metabolic rate being a metabolic rate of mammary tissue of one or a group animals not administered the drug, dietary supplement, diet, or other composition, then the drug, dietary supplement, diet, or other composition does not affect milk production of the animal.
  • tissue-specific metabolic rate of the animal is less than a control tissue- specific metabolic rate, the control tissue-specific metabolic rate being a metabolic rate of one or a group animals not administered the drug, dietary supplement, diet, or other composition, then the drug, dietary supplement, diet, or other composition has a positive affect on milk production of the animal.
  • the tissue-specific metabolic rate of the animal is greater than a control tissue-specific metabolic rate, the control tissue-specific metabolic rate being a metabolic rate of one or a group animals not administered the drug, dietary supplement, diet, or other composition, then the drug, dietary supplement, diet, or other composition has a negative effect on milk production of the animal.
  • the present invention also features methods of testing a drug, dietary supplement, diet, or composition ex vivo.
  • the method may feature obtaining samples from the animal and treating the samples with the drug, dietary supplement, diet, or composition in culture to determined wither or not there is an affect of the drug, dietary supplement, diet, or composition on the production of reducing equivalents (e.g., metabolic rate)
  • the term “baseline,” referring to metabolic rate or other parameter, may refer to an amount predetermined by the industry or by the user.
  • the baseline may be predetermined by the user by testing the animal’s metabolic rate (or milk production) prior to administration of the drug or composition.
  • the baseline is predetermined by other individuals, e.g., national averages, breed averages, etc.
  • the present invention also features methods for treating animals to improve milk production.
  • the method may comprise determining an amount of a drug, dietary supplement, diet, or other composition to administer to achieve a particular milk production (e.g., using the methods or a combination of methods described herein), and administering the dose of the drug, dietary supplement, diet, or other composition to achieve the desired milk production.
  • the present invention also features methods for treating animals to improve feed efficiency.
  • the method may comprise determining an amount of a drug, dietary supplement, diet, or other composition to administer to achieve a particular feed efficiency (e.g., using the methods or a combination of methods described herein), and administering the dose of the drug, dietary supplement, diet, or other composition to achieve the desired feed efficiency.
  • the terms percentile, percentile level, threshold, threshold level, and/or baseline may refer to a predetermined amount or level that is determined by the user or by the industry.
  • the threshold level or percentile level is an industry average.
  • the threshold level or percentile level is set by the user.
  • the threshold level may be unique to a particular breed or herd.
  • the threshold level or percentile level may depend on the desired feed efficiency, milk production, etc.
  • the threshold or percentile is the 50 th percentile or average.
  • the threshold or percentile is the 5 th percentile.
  • the threshold or percentile is the 1Q !h percentile.
  • the threshold or percentile is the 15 th percentile. In some embodiments, the threshold or percentile is the 20 th . In some embodiments, the threshold or percentile is the 25 th percentile. In some embodiments, the threshold or percentile is the 30 in percentile. In some embodiments, the threshold or percentile is the 35 h percentile. In some embodiments, the threshold or percentile is the 40 th percentile. In some embodiments, the threshold or percentile is the 45 ih percentile. In some embodiments, the threshold or percentile is the 55 Ih percentile. In some embodiments, the threshold or percentile is the 60 th percentile. In some embodiments, the threshold or percentile is the 65 th percentile.
  • the threshold or percentile is the 70 ih percentile. In some embodiments, the threshold or percentile is the 75 ih percentile. In some embodiments, the threshold or percentile is the 80 th percentile. In some embodiments, the threshold or percentile is the 85 th percentile. In some embodiments, the threshold or percentile is the 90 !h percentile. In some embodiments, the threshold or percentile is the 95 th percentile. In some embodiments, the threshold or percentile is the 5 Ih percentile. In some embodiments, the threshold or percentile is the 99 th percentile. In some embodiments, the threshold or percentile is the 5 ih percentile.
  • the present invention is not limited to the aforementioned thresholds or percentiles.
  • the present invention is not limited to the aforementioned means of determining the thresholds or percentiles.
  • features and advantages of the methods of the present invention include, but are not limited to: (a) the ability to test tissue-specific metabolic rate; (b) the ability to test for genetic, nutrition, endocrine, and physiological effects on tissue-specific metabolic rate; (c) the ability to test for effects either in vivo or ex vivo (d) the ability to test the effect on metabolic rate of any water or DMSG soluble compound; (e) the ease of application and measurement (includes fluorescence change or color change, which can be measured from a photograph); (f) the use of a cumulative signal, which is more sensitive that a simple measure of oxygen consumption and allows for differentiation of small differences between animals; (g) the simplicity, including only the mixture of a few solutions; and (h) the ability to scale this up for simultaneous measure of 1000s of samples.
  • FIG. 1A shows that skeletal muscle biopsies cause a linear increase in fluorescent signal with time indicating that the skeletal muscle tissue continues to produce reducing equivalents and remains viable through the incubation period. Moreover, it is shown that this signal is sensitive to fasting (16 hr fast).
  • FIG. 1 B shows that liver biopsies cause a linear increase in fluorescent signal with time indicating that the liver tissue continues to produce reducing equivalents and remains viable through the incubation period. Moreover, it is shown that this signal is not sensitive to fasting (16 hr fast).
  • FIG. 1C shows the 4h metabolic rate from figures 5A and 5B (fluorescence change/ng DNA). Metabolic rate of skeletal muscle biopsies is decreased by fasting (16b), but fasting did not affect liver biopsy metabolic rate. This establishes that the assay can be applied to assess the effect of nutritional state on tissue specific metabolic rate.
  • FIG. 1 D shows glucose (1 mM) in the media increases skeletal muscle biopsy metabolic rate measured as relative change in fluorescence/mg tissue. This establishes that the assay can be applied to assess the effect of nutrients on tissue specific metabolic rate.
  • FIG. 1 E shows Isoproterenol, a beta-adrenergic receptor agonist, increases skeletal muscle metabolic rate at high glucose concentrations (2 mM). This establishes that the assay can be applied to assess the effect of drugs on tissue specific metabolic rate.
  • F!G. 1 F shows metabolic rates (expressed as fluorescence change/mg tissue) of tissue biopsies (e.g., brown adipose tissue (BAT), white adipose tissue (WAT), white skeletal muscle, red skeletal muscle, heart, kidney, and liver) differ across tissues and with age of the mouse (1 month, 3 months).
  • tissue biopsies e.g., brown adipose tissue (BAT), white adipose tissue (WAT), white skeletal muscle, red skeletal muscle, heart, kidney, and liver
  • BAT brown adipose tissue
  • WAT white adipose tissue
  • red skeletal muscle red skeletal muscle
  • FIG. 2 shows metabolic rates (as changes in fluorescence over time) of many tissues (e.g., brown adipose tissue (BAT), white adipose tissue (WAT), white skeletal muscle, red skeletal muscle, heart, kidney, and liver) in fed and fasted mice.
  • tissues e.g., brown adipose tissue (BAT), white adipose tissue (WAT), white skeletal muscle, red skeletal muscle, heart, kidney, and liver
  • FIG. 3 shows that mammary gland biopsy metabolic rate may be used to predict milk production.
  • Ex vivo mammary gland metabolic rate (top panel), as measured using the assay described in this patent, predicts ex vivo mammary gland lactose production (bottom panel) in response to heat stress (days 13-19 of pregnancy 35°C/50% humidity), maintenance at room temperature (RT; 22 ⁇ 24°C/50% humidity) with ad libitum access to feed, or maintenance at room temperature (22-24°C/50% humidity) with feed restricted to that consumed ad libitum by heat stressed animals (pair-fed; PF).
  • FIG. 4A shows that biopsies from mature fully-grown cows have a lower metabolic rate than those collected from young growing cattle.
  • Variability in FC/4b induced by skeletal muscle biopsies from young and mature cows is robust. This variability may be important for improving genetics for efficiency.
  • skeletal muscle metabolic rate There was no breed difference in skeletal muscle metabolic rate between Hereford and Angus cattle.
  • intrabreed animal-to-animal variability in skeletal muscle metabolic rate FC/4b is extensive in Hereford and Angus cattle. This variability may be important for improving genetics for efficiency.
  • HF-HS high fiber-high starch
  • HF-LS high fiber-low starch
  • LF-HS low fiber-high starch
  • LF-LS low fiber-low starch
  • FIG. 6 establishes that the relative rank of animals based on skeletal muscle metabolic rate was maintained across dietary treatments.
  • Treatments included either a high (HS) or low (LS) rumen degradable starch source and either a high (HF) or low (LF) rumen degradable fiber source.
  • Animal numbers are arbitrary and reflect the animal identifier assigned by the farm. These identifiers are included in the legend to show consistence of animal rankings across diets. This figure establishes that rankings of similarly treated animals based on skeletal muscle metabolic rate can effectively be maintained independent of diet.
  • FIG. 7 shows the skeletal muscle metabolic rate of growing steers (as indicated on the X-axis, relative fluorescent change) is directly related to average daily gain (ADG) (top panel), does not relate to mean dry matter intake (DM! (middle panel), and is inversely related to feed to gain ratio (F:G) (bottom panel). (Each dot represents an individual animal.) The dotted line shows a best-fit linear regression of the performance variable on relative fluorescence. The R 2 values presented reflect the coefficient of determination for each regression. This data establishes that skeletal muscle reducing equivalent (NADH, FADFi 2 , etc.), used as a proxy for tissue metabolic rate, can be used to predict growth and feed efficiency in a growing animal.
  • ADG average daily gain
  • DM mean dry matter intake
  • F:G feed to gain ratio
  • the present invention provides methods of measuring metabolic rates of animas (or humans), wherein the methods feature measuring reducing equivalents (e.g., NADH, FADH 2 , NADP(H), Coenzyme Q, etc.).
  • the methods may comprise obtaining a tissue biopsy from the animal (e.g., skeletal muscle tissue biopsy, mammary tissue biopsy, etc.). Biopsies may be obtained by an appropriate means, e.g., using a needle biopsy tool, via crude dissection, etc.
  • the method may comprise putting at least a portion of the biopsy in appropriate media in a plate or dish (e.g., 12-we!i plate, 24-we!i plate, 96-we!i plate, etc ).
  • the biopsy tissue in the dish is then subjected to a reducing equivalent indicator, e.g., a dye.
  • a reducing equivalent indicator e.g., a dye.
  • the biopsies are then read, e.g., color (e.g., RGB analysis), absorbance, fluorescence, and/or any other appropriate parameter may be measured to assess change in signal.
  • the measured change is indicative of the degree of reducing equivalent (e.g., NADH, FADH 2 , NADP(H), Coenzyme Q, etc.) production.
  • concentration of reducing equivalent indicator e.g., resazurin, MTT, AlamarBlue®, PrestoB!ue®
  • concentration of reducing equivalent indicator may be titrated to meet specific needs; titration of concentration can alter sensitivity of the assay.
  • the present invention is not limited to the aforementioned reducing equivalent indicators.
  • resazurin assays for measuring NADH H + production
  • a biopsy is collected from an animal and immediately put into a well of a 96-weli plate containing Duibecco’s Modified Eagle Medium (DMEM) with Pen/Strep and put into a 37°C incubator with 95% 0 2 5% CO2. After 1 h equilibration, biopsies are moved into a well filled with 300 ul DMEM supplemented with 0.1 % DMSO, Pen/Strep and 0.16% 10X resazurin.
  • DMEM Modified Eagle Medium
  • FIG. 1A, FIG. 1 B, FIG. 1C, FIG. 1 D, FIG. 1 E, and FIG. 1 F show the application of the resazurin-based assay to homeothermic tissue collected from mice.
  • FIG. 1A shows skeletal muscle metabolic rate linearly increases with time to 4 hours and is sensitive to fasting.
  • FIG. 1 B shows liver metabolic rate (linearly increases with time and is not sensitive to fasting.
  • FIG. 1 C shows metabolic rate (expressed as fluorescence change/ng DNA) is decreased by fasting in skeletal muscle.
  • FIG. 1 D shows glucose in the media increases skeletal muscle metabolic rate (sensitive to ex vivo nutrient application).
  • FIG. 1A shows skeletal muscle metabolic rate linearly increases with time to 4 hours and is sensitive to fasting.
  • FIG. 1 B shows liver metabolic rate (linearly increases with time and is not sensitive to fasting.
  • FIG. 1 C shows metabolic rate (expressed as fluorescence change/ng DNA) is decreased by fasting in skeletal muscle.
  • FIG. 1 E shows Isoproterenol, a beta-adrenergic receptor agonist, increases skeletal muscle metabolic rate at high glucose concentrations (sensitive to drug application).
  • FIG. 1 F shows metabolic rates of tissues differ across tissues and with age of the mouse (1 month, 3 months).
  • FIG. 2 shows the metabolic rates of various tissues, e.g., brown adipose tissue (BAT), white adipose tissue (WAT), white skeletal muscle, red skeletal muscle, heart, kidney, and liver in fed and fasted mice, showing the effect of a physiological change (fasting) on metabolic rate (as measured by the 4br fluorescence change/mg tissue).
  • BAT brown adipose tissue
  • WAT white adipose tissue
  • FIG. 2 shows the metabolic rates of various tissues, e.g., brown adipose tissue (BAT), white adipose tissue (WAT), white skeletal muscle, red skeletal muscle, heart, kidney, and liver in
  • White adipose tissue and liver were the two tissues that were affected by fasting when measured as the 4hr fluorescence change per mg tissue. Skeletal muscle tissues were unaffected. Without wishing to limit the present invention to any theory or mechanism, DNA may be a preferred correction factor.
  • the present invention is not limited to the aforementioned methods and compositions for measuring reducing equivalents.
  • tissue metabolic rate is associated with a higher feed efficiency and/or a higher amount of productivity (e.g., higher production of milk, muscle, eggs, etc ).
  • the present invention provides methods for identifying (and/or) selecting animals with high feed efficiency.
  • the present invention also provides methods of identifying animals with increased productivity (e.g., egg production, milk production, etc.), methods of predicting animals with high productivity, and methods of selecting animals with high productivity.
  • the methods herein select for lower tissue-specific metabolic rates (e.g., lower skeletal muscle metabolic rates) and/or lower basal metabolic rates, etc.
  • a tissue from an animal e.g., skeletal muscle
  • determines the metabolic rate by determining reducing equivalent production (e.g., an amount, a change in, etc.).
  • the animal or tissue from the animal e.g., skeletal muscle
  • a reducing equivalent indicator is evaluated by assessing the change in fluorescence, absorbance (570-800 nM when using resazurin), or by color.
  • the resulting metabolic rate is then compared to the range of known changes in
  • tissue specific changes in fluorescence, absorbance, or color are corrected for DNA, protein, or mass of the sample.
  • the reducing equivalents are used in mathematical models may be used in conjunction with the reducing equivalent (metabolic rate) data to determine or predict feed efficiency or productivity, e.g., weight gain, egg production, milk production, etc.
  • feed efficiency or productivity e.g., weight gain, egg production, milk production, etc.
  • a prospective study of a cohort of dairy cows may be used to predict high milk production.
  • Mammary tissues may be obtained and tested for metabolic rate, and milk production can be determined for each subject.
  • a candidate scoring function may be chosen to stratify future tested animals into a category of high milk production or low milk production (or other different or additional categories). For example, those animals with high mammary gland metabolic rates may be selected as animals predicted to have high milk production.
  • the methods of the present invention feature selection of animals with a low basal metabolic rate (e.g., a low tissue-specific metabolic rate). In some embodiments, the methods of the present invention feature selection of animals with a high basal metabolic rate (e.g., a high tissue-specific metabolic rate).
  • mammary gland metabolic rate may be used to predict milk production.
  • FIG. 3 shows that ex vivo mammary gland metabolic rate (top panel) predicts ex vivo mammary gland lactose production (bottom panel) in response to heat stress (days 13-19 of pregnancy 35°C/50% humidity), maintenance at room temperature (RT; 22-24°C/50% humidity) with ad libitum access to feed, or maintenance at room temperature (22-24°C/50% humidity) with feed restricted to that consumed ad libitum by heat stressed animals (pair-fed; PF).
  • FIG. 4A and FIG. 4B show metabolic rate in young calves and fully-grown cows (Angus and Hereford).
  • FIG. 4A shows that mature fully-grown cows have a lower metabolic rate than young growing cattle.
  • FIG. 4B shows that there was no average difference in metabolic rate in Hereford and Angus cattle.
  • Variability in FC/4h is extensive in young and mature cows and in Hereford and Angus cattle. This variability is important for improving genetics for efficiency.
  • the methods of the present invention may also be used to study the efficiency of a particular tissue important to productivity (e.g., mammary tissue important for milk production).
  • the present invention also provides methods for identifying susceptibility or resistance to obesity in animals (or humans), e.g., for determining whether a subject (e.g., an animal, human, etc.) has a likelihood of developing obesity or becoming overweight, or whether the animal or human may be resistant to obesity.
  • a subject e.g., an animal, human, etc.
  • a prospective study of a cohort with known outcomes may be used develop a relationship between outcome and metabolic rate (e.g., calculate one or more candidate scoring functions, etc.).
  • a cohort of patients may be evaluated, wherein each individual provides a skeletal muscle biopsy, which is tested for metabolic rate by measuring reducing equivalent production (e.g., an amount, a change in, etc.).
  • the resulting skeletal muscle metabolic rates may be plotted against the weight change in response to a given lifestyle intervention.
  • a long-term longitudinal study could be performed to assess body weight change with time.
  • outcomes may be grouped based on known standards for categorizing individuals as non-overweight, overweight, and obese.
  • a body mass index (BMI) from 25 0 to 29.9 is defined as overweight, and a BMI of 30 or more is defined as obese.
  • BMI values may be used to determine the outcomes of the individuals in the cohort.
  • one or more cutoffs may be selected to stratify the patients into the categories described above.
  • a non-limiting example of a mechanism for determining cutoffs of the categories may be a receiver operating characteristic (ROC) curve.
  • ROC curves allow users to balance the sensitivity of a model (for example to prioritize capturing as many“positive” or“likely to become overweight/obese” subjects as possible) with the specificity of the model (for example minimizing severity of the model (for example minimizing bromine-positives for likely to become overweigbt/obese candidates”).
  • the selected scoring function (and optionally a cutoff determined by a ROC curve) provides a pre-determined threshold used for evaluating subjects being tested for susceptibility to obesity.
  • the present invention also features methods for selection of broodstock, e.g., selecting broodstock with high feed efficiency, selecting broodstock with high productivity, etc.
  • the broodstock selection may feature testing a mother's or father’s tissue-specific metabolic rate (e.g., skeletal muscle, etc ), which can be indicative of the feed efficiency and/or productivity of the progeny.
  • the present invention also provides methods for determining an effect of genetics, environmental stimuli, a drug treatment (e.g., antibiotics), physiological treatment (e.g., exercise), a dietary supplement, a diet, or nutritional treatment on the metabolic rates (e.g., basal metabolic rate, tissue-specific metabolic rate) of animals of interest, and thus the effect on feed efficiency, productivity, etc.
  • a drug treatment e.g., antibiotics
  • physiological treatment e.g., exercise
  • a dietary supplement e.g., a diet
  • nutritional treatment e.g., basal metabolic rate, tissue-specific metabolic rate
  • a group of animals e.g , cattle
  • skeletal muscle metabolic rates may be determined to assess what effect the nutritional treatment had on the metabolic rate and potential feed efficiency, productivity, etc.
  • the present invention features high-throughput methods for assessing energy expenditure for selection to improve efficiency.
  • the methods below describe a muscle biopsy technique for stratifying cattle by skeletal muscle nicotinamide adenine dinucleotide reduction rate for assessing the metabolic rate of skeletal muscle biopsies in cattle.
  • the technique may be applied to allow for genetic selection for growth or feed efficiency across species.
  • the present invention is not limited to the methods, assays, and compositions described herein.
  • Tissue biopsy metabolic activity assessed using the oxidation-reduction indicator Resazurin, may serve as a proxy to assess energy expenditure associated with maintenance in non-growing animals or growth rate in growing animals. These methods may evaluate the repeatability, practicality, and sensitivity of a Resazurin-based assay for ranking bovine skeletal muscle biopsies based on metabolic activity.
  • Six yearling Holstein heifers (BW 330 ⁇ 11 3 kg) were fed 4 dietary treatments consisting of high or low rumen degradable starch and fiber arranged factor!ally in a partially replicated Latin Square design.
  • Periods were 18 d, with 3 d diet transition, 14 d diet adaptation, and 1 d sample collection
  • Semitendinosus biopsies were collected into ice-cold Dulbecco’s modified eagle media (DMEM) from each heifer during each period. Analysis was initiated within an hour of sample collection. To assess tissue metabolic rate, biopsies were transferred to DMEM with Resazurin and incubated at 37°C. Fluorescence of each sample was read at time 0 and at 15-minute intervals for two hours. Change in fluorescence was representative of skeletal muscle reducing equivalent production (e.g., NADH).
  • DMEM modified eagle media
  • this method can rank individual animals based on metabolic activity and detect differences in metabolic activity associated with dietary changes.
  • diets also contained soybean meal (HS-HF 9.3, % DM; HS-LF 17.1 , % DM; LS-HF 9.95, % DM; LS-LF 15.3, % DM), blood meal (HS-HF 3.78, % DM; HS-LF 0.00, % DM; LS-HF 4.37, % DM; LS-LF 0.040, % DM), and corn gluten feed (HS-HF 3.26, % DM; HS-LF 0.00, % DM; LS-HF 1.65, % DM; LS-LF 7.22, % DM) to make them isonitrogenous.
  • soybean meal HS-HF 9.3, % DM; HS-LF 17.1 , % DM; LS-HF 9.95, % DM; LS-LF 15.3, % DM
  • blood meal HS-HF 3.78, % DM; HS-LF 0.00, % DM; LS-HF 4.37, % DM
  • a 10 cm wide area 5 cm to 35 cm ventral to the point of the ischium was shaved and scrubbed three times with betadine and isopropano!.
  • 10 ml of iidocaine was administered subcutaneously in 5 to 6 locations radially arrayed 2 cm externally to the biopsy site.
  • the target biopsy site was 20 cm ventral to the point of the ischium.
  • Muscle tissue samples were collected by making a 1 cm incision through the skin with a #20 scalpel blade, inserting a 20 gauge biopsy needle (Bard® Mission® Disposable Core Biopsy Instrument) to a 4 cm depth, and depressing the needle collection sheath to obtain a sample.
  • sample mass sample mass, collection site within the muscle, and other unknown factors
  • sample mass sample mass, collection site within the muscle, and other unknown factors
  • sample mass sample mass, collection site within the muscle, and other unknown factors
  • Samples were not weighed after collection because an analytical balance was not available at the farm.
  • the incision site was sealed using monofilament #2 suture wire, cleaned with isopropanol, and sprayed with adhesive bandage.
  • the right semitendinosus was sampled in periods 1 and 3 and the left semitendinosus was sampled in periods 2 and 4.
  • the structurally intact core samples were placed in individual wells of a 96 well plate filled with a pre-test solution.
  • the pre-test solution and contained 30 ml DMEM (Fisher Science 21-041-025), 7.5 mg Fungizone (Fisher Science 15-290-026), 0.12 mg Chloramphenicol (Fisher Science BP904-100), and 0.03 mg Ampicillin (Fisher Science AAJ6097714). After ail samples were collected, they were transferred from the pre-test solution into individual wells of a 96 well plate filled with resazurin test assay solution.
  • test solution was identical to the pre-test solution with 1.6% AiamarBiue® (resazurin-based reagent, Thermo Scientific Y00-10Q) added. Solutions were mixed immediately prior to biopsy collection, filtered using a sterile 0.22 pM filter, and warmed to 37 " C before use.
  • AiamarBiue® resazurin-based reagent, Thermo Scientific Y00-10Q
  • the live muscle tissue samples were transported to the lab in the pre-test solution, transferred to the test solution, and analyzed. Analysis was initiated within one hour of tissue collection to ensure tissue viability.
  • the test solution plate was incubated in the plate reader (Spectramax M5; Molecular Devices, LLC, San Jose, CA) at 37°C Fluorescence was read at time 0 and every 15 minutes for 2 hours using excitation and emission wavelengths of 530 and 590 nm, respectively.
  • Soft Max Pro 8.1 (Molecular Devices, LLC, San Jose, CA) was used to quantify resulting emissions, and relative fluorescence (standardized to time 0) was calculated at each time point for each sample.
  • VFA contribution to muscle is dependent upon individual VFA metabolism. Less than 30% of acetate, 40-55% of propionate, and minimal butyrate is available to the periphery.
  • Glucose contribution to skeletal muscle in ruminants is due to gluconeogenesis. Hepatic uptake of propionate, valerate, and isobutyrate allows for increased gluconeogenic substrate. If the different starch sources contributed to different profiles of absorbed VFA, it is possible that the absorbed VFA profiles contributed to the effect of ruminaliy degradable starch on skeletal muscle metabolic activity. Independent of the mechanism driving this dietary effect, the results suggest the assay can be applied to understand the metabolic effects of ration changes.
  • the metabolic activity of a ruminant is a function of body mass and metabolic flux during an inactive, tbermoneutra! environment. These differences in metabolic flux contribute to variability in feed efficiency.
  • the individual metabolic flux can be influenced by genetic potential, activity and behavior, environment, and heifer rearing practices. Referring to FIG 7, the average skeletal muscle metabolic activity (expressed as relative fluorescence) of each individual was paired with dry matter intake (DMI), average daily gain (ADG), and calculated feed to grain ratio (F:G).
  • a rancher owns a population of cattle and is interested in choosing the animals with the highest feed efficiency for breeding purposes. For each adult animal, she obtains a skeletal muscle tissue sample and measures the metabolic rate by measuring reducing equivalents.
  • the metabolic rate of the skeletal muscle tissue is inversely related to the feed efficiency, so the farmer chooses to breed the animals with the metabolic rates that are in the lowest 25%, which would have the highest feed efficiency. For example, for a group of 100 animals, the rancher chooses the 25 animals with the lowest skeletal muscle metabolic rate. Those animals in the 25 th percentile are selected for breeding purposes. The remaining 75% of the animals are not used for breeding
  • a farmer owns a population of cattle and is interested in choosing the animals with the highest milk production for breeding purposes. For each animal, he obtains a mammary tissue sample and measures the metabolic rate by measuring reducing equivalents.
  • the metabolic rate of the mammary tissue is directly related to the potential milk production.
  • the farmer has previously done studies to determine the amount of milk produced per day (gallons per day) based on a particular metabolic rate of mammary tissue. For example, a metabolic rate of 1000 (fluorescence change per mg tissue) or more predicts the animal will produce at least 6 gallons of milk per day. A metabolic rate of 2000 (fluorescence change per mg tissue) or more predicts the animal will produce at least 9 gallons of milk per day. A metabolic rate of 3000 (fluorescence change per mg tissue) predicts the animal will produce at least 12 gallons per day.
  • a rancher owns 40 cattle and is interested in determining how Drug A will affect the feed efficiency of the cattle. For each animal, she obtains a skeletal muscle tissue sample and measures the metabolic rate by measuring reducing equivalents. She calculates the average metabolic rate for the group of animals.
  • the rancher calculates that treatment with Drug A lowered the average metabolic rate of the animals by 20%. This correlates with a 20% change in average feed efficiency of the animals as well.
  • a farmer owns 100 cows and is interested in determining how Drug B will affect milk production of the animals. For each animal, he obtains a mammary tissue sample and measures the metabolic rate by measuring reducing equivalents. He calculates the average metabolic rate for the group of animals.
  • descriptions of the inventions described herein using the phrase“comprising” includes embodiments that could be described as “consisting of”, and as such the written description requirement for claiming one or more embodiments of the present invention using the phrase“consisting of is met.

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Abstract

L'invention concerne des procédés d'identification d'animaux qui sont génétiquement supérieurs, des médicaments, des stratégies nutritionnelles, ou des manipulations physiologiques qui améliorent l'efficacité d'alimentation ou la productivité d'animaux, par exemple, la sélection d'animaux qui sont génétiquement supérieurs pour une efficacité ou une productivité d'alimentation en fonction des taux métaboliques de tissus particuliers, les taux métaboliques de certains tissus tels que le muscle squelettique étant inversement proportionnels à l'efficacité de l'alimentation, tandis que les taux métaboliques d'autres tissus tels que la glande mammaire sont directement proportionnels à la production de lait. Ainsi, les animaux à faible taux métabolique du muscle squelettique sont généralement plus efficaces pour l'alimentation, par exemple, le gain de poids par unité d'aliment. Les procédés de l'invention peuvent être utilisés pour améliorer la génétique, la nutrition et la manipulation ou des animaux ou des produits à base d'animaux produits de manière plus efficace, par exemple la production de viande, la production de lait, la production d'œufs, la production de laine, etc. Les procédés de l'invention peuvent également être utilisés pour déterminer des valeurs de reproduction estimées d'animaux à des fins d'efficacité d'alimentation, de croissance ou de production.
EP18878766.7A 2017-11-15 2018-11-15 Procédés de mesure de la production équivalente de réduction par des tissus pour déterminer des taux métaboliques et procédés d'utilisation Pending EP3709818A4 (fr)

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