WO2007061314A2 - Use of fatty acid analogues - Google Patents

Use of fatty acid analogues Download PDF

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Publication number
WO2007061314A2
WO2007061314A2 PCT/NO2006/000424 NO2006000424W WO2007061314A2 WO 2007061314 A2 WO2007061314 A2 WO 2007061314A2 NO 2006000424 W NO2006000424 W NO 2006000424W WO 2007061314 A2 WO2007061314 A2 WO 2007061314A2
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WO
WIPO (PCT)
Prior art keywords
group
fish
atom
feed
carbon atoms
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PCT/NO2006/000424
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English (en)
French (fr)
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WO2007061314A3 (en
Inventor
Kjell-Arne Rorvik
Magny Thomassen
Rolf Berge
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Berge Biomed As
Thia Medica As
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Priority to EP06824343A priority Critical patent/EP1959751A2/en
Publication of WO2007061314A2 publication Critical patent/WO2007061314A2/en
Publication of WO2007061314A3 publication Critical patent/WO2007061314A3/en
Priority to NO20082546A priority patent/NO20082546L/no

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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/20Inorganic substances, e.g. oligoelements
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K50/00Feeding-stuffs specially adapted for particular animals
    • A23K50/80Feeding-stuffs specially adapted for particular animals for aquatic animals, e.g. fish, crustaceans or molluscs
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/158Fatty acids; Fats; Products containing oils or fats
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K40/00Shaping or working-up of animal feeding-stuffs
    • A23K40/25Shaping or working-up of animal feeding-stuffs by extrusion
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals

Definitions

  • the present application pertains to use of a feed comprising
  • R" is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R' contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a CH 2 group, a SO group and a SO 2 group; and R" is a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms; or
  • R1 , R2, and R3 represent i) a hydrogen atom; or ii) a group having the formula CO-R in which R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or iii) a group having the formula CO-(CH 2 ) 2 n+i-X-R', wherein X is a sulphur atom, a selenium atom, an oxygen atom, a CH 2 group, a SO group or a SO 2 group; n is an integer of 0 to 11 ; and R' is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R' contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a CH
  • A1 , A2 and A3 are chosen independently and represent an oxygen atom, a sulphur atom or an N-R4 group in which R4 is a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms; wherein R1, R2, and R3 represent i) a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 23 carbon atoms; or ii) a group having the formula CO-R in which R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or iii) a group having the formula CO-(CH 2 Wi-X-R'.
  • X is a sulphur atom, a selenium atom, an oxygen atom, a CH 2 group, a SO group or a SO 2 group
  • n is an integer of 0 to 11
  • R' is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R' contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a CH 2 group, a SO group and a SO 2 group; iv) an entity selected from the group comprising -PO 3 CH 2 CHNH 3 COOH (serine), PO 3 CH 2 CH 2 NH 3 (ethanolamine), PO 3 CH 2 CH 2 N(CHs) 3 (choline), PO 3 CH 2 CHOHCH 2 OH (glycerol) and PO 3 (CHOH) 6 (inositol); wherein R1 , R
  • IPPN Infectious pancreatic necrosis
  • IPNV The IPN virus
  • Salmonids such as Atlantic salmon, rainbow trout (Oncorhynchus mykiss L.) and brown trout (Salmo trutta L.), but also a number of other species (Mortensen et al. 1999; Bruno 2004).
  • Atlantic salmon IPN occurs in the freshwater period, but in recent years disease outbreaks have increased after sea transfer.
  • smolt transferred to seawater in spring (1+) versus smolt transferred in autumn (0+) and outbreak of IPN have shown that there is a much higher mortality among 1+ smolt compared to 0+ smolt.
  • the use of the feed according to the present invention is for feeding fish during time periods where the requirements for energy of said fish is increased, in order to improve the health of said fish.
  • TTA is a non ⁇ -oxidizable fatty acid analogue, belonging to a group of compounds comprising: (1) a compound represented by the general formula R"-COO-(CH 2 ) 2 n + i-X-R ⁇ wherein X is a sulphur atom, a selenium atom, an oxygen atom, a CH 2 group, a SO group or a SO 2 group; n is an integer of 0 to 11 ; and R' is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R' contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a CH 2 group, a SO group and a SO 2 group; and R" is a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms; or
  • R1 , R2, and R3 represent i) a hydrogen atom; or ii) a group having the formula CO-R in which R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or iii) a group having the formula CO-(CH 2 ) 2n +i-X-R', wherein X is a sulphur atom, a selenium atom, an oxygen atom, a CH 2 group, a SO group or a SO 2 group; n is an integer of O to 11 ; and R' is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R' contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a CH 2 group
  • A1 , A2 and A3 are chosen independently and represent an oxygen atom, a sulphur atom or an N-R4 group in which R4 is a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms; wherein R1 , R2, and R3 represent i) a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 23 carbon atoms; or ii) a group having the formula CO-R in which R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or iii) a group having the formula CO-(CH 2 ) 2n+ i-X-R', wherein X is a sulphur atom, a selenium atom, an oxygen atom, a CH 2
  • R1 , R2 or R3 is an alkyl
  • At least one of R1 , R2 or R3 is an alkene.
  • At least one of R1 , R2 or R3 is an alkyne.
  • At least one of R1 , R2 or R3 is tetradecylthioacetic acid.
  • At least one of R1 , R2 or R3 is tetradecylselenoacetic acid.
  • X is a sulphur or selenium atom.
  • Preferred embodiments of the compounds according to the invention are tetradecylthioacetic acid (TTA), tetradecylselenoacetic acid and 3-Thia-15- heptadecyne.
  • n is 0 or 1.
  • said compound is a phospholipid, wherein said phospholipid is selected from the group comprising phosphatidyl serine, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl inositol, phosphatidyl glycerol, diphosphatidyl glycerol.
  • said compound is a triacylglycerol, most preferably comprising tetradecylthioacetic acid (TTA).
  • TTA tetradecylthioacetic acid
  • said compound is a diacylglycerol.
  • said compound is a monoacylglycerol. In a preferred embodiment of a compound according to the invention said compound is a non ⁇ -oxidizable fatty acid.
  • said compound is the phosphatidyl choline derivative 1 ,2-ditetradecylthioacetoyl-s/7-glycero-3- phosphocholine.
  • said compound is the phosphatidyl ethanolamine derivative i ⁇ -ditetradecylthioacetoyl-sn-glycero-S- phosphoethanolamine.
  • A1 and A3 both represent an oxygen atom, while A2 represent a sulphur atom or an N-R4 group in which R4 is a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms.
  • the compounds according to the invention are analogues of naturally occurring compounds, and as such are recognized by the same systems which process the natural compounds, including the enzymes that ⁇ - and in some cases ⁇ - oxidize natural long chain fatty acids.
  • the analogues differ from their naturally occurring counterparts in that they cannot be completely oxidized in this manner.
  • the compounds according to the invention may be non ⁇ -oxidizable fatty acid analogues, as represented by the formula R 11 CCO-(CH 2 WrX-R'- However, said compounds may also be more complex structures derived from one or more of said non ⁇ -oxidizable fatty acid analogues, as represented by the general formulas (I) or (II). These compounds are analogues of naturally occurring mono-, di-, and triacylglycerols, or phospholipids including phosphatidyl serine, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl inositol, phosphatidyl glycerol, and diphosphatidyl glycerol.
  • Said compounds may also comprise a substitution in the glycerol backbone, as shown in formula (II).
  • Said substitution of the oxygen(s) is achieved by replacing the oxygen(s) with sulphur or a nitrogen containing group. This may block hydrolysis before uptake by the intestines, thus increasing the bioavailability of the compounds.
  • the above complex structures derived from one or more of said non ⁇ -oxidizable fatty acid analogues have their effect because the fatty acid analogues they comprise are not capable of being fully ⁇ -oxidized.
  • Said complex structures may have an effect as complete structures, and as naturally resulting degradation products comprising the fatty acid analogues.
  • the compounds are not able to be fully ⁇ -oxidized, they will build up, and this triggers an increase in the ⁇ - oxidation of naturally occurring fatty acids. Many of the effects of the compounds according to the invention are due to this increase in ⁇ -oxidation.
  • ⁇ -oxidation a fatty acid is enzymatically oxidized cleaved between carbons 2 and 3 (when counting from the carboxylic end of the fatty acid), resulting in the removal of the two carbon atoms on either side of the oxidation site as acetic acid. This step is then repeated on the now two carbons shorter fatty acid, and repeated again until the fatty acid is fully oxidized, ⁇ -oxidation is the usual way in which the majority of fatty acids are catabolized in vivo.
  • the ⁇ -oxidation blocking by the compounds according to the invention is achieved by the insertion of a non- oxidizable group in the X position in the formula of the present invention. Because the mechanism for ⁇ -oxidation is well known, X is defined as S, O, SO, SO 2 , CH 2 or Se.
  • the compounds may contain more than one block, i.e. in addition to X, R' may optionally comprise one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a CH 2 group, a SO group and a SO 2 group.
  • R' may optionally comprise one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a CH 2 group, a SO group and a SO 2 group.
  • R' may optionally comprise one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a CH 2 group, a SO group and a SO 2 group.
  • one may insert two or three sulphurs as X to induce a change in the degradation of the fatty acid and thus a modulated effect. Multiple sulphur atoms
  • n is an integer of O to 11.
  • fatty acids which normally undergo ⁇ -oxidation are usually 14 to 24 carbon atoms long, and this length is therefore most ideal for undergoing enzymatic ⁇ -oxidation.
  • the ranges of n and R' are thus given so that the fatty acid analogues will cover this range.
  • option ii) of formulas (I) and (II) and define R to have 1 to 25 carbon groups
  • option i) of formula (II) define the alkyl group to contain from 1 to 23 carbon atoms, to be analogous to naturally occurring compounds.
  • the total number of carbon atoms in the fatty acid backbone is preferably between 8 and 30, most preferably between 12 and 26. This size range is also desirable for the uptake and transport through cell membranes of the fatty acid analogues of the present invention.
  • fatty acid analogues and other compounds represented by the general formulas (I) and (II), (which comprise said fatty acid analogue(s),) which block ⁇ -oxidation at different distances from the carboxylic end of the analogues as the compounds of the present invention all do indeed block ⁇ -oxidation, even if the effect thereof can be modulated.
  • This modulation will after all differ under varying conditions; in different tissues, with varying dosages, and by changing the fatty acid analogue so that it is not so easily broken down, as will be described next.
  • fatty acid analogues as described with a block in the X position cannot undergo ⁇ -oxidation, they may still undergo ⁇ -oxidation.
  • This is a much less common and slower biological process, which oxidizes the fatty acid not from the carboxylic end, but rather from the methyl/hydrophobic head group, here termed R'.
  • R' methyl/hydrophobic head group
  • the carbon atom at the ⁇ -end of the fatty acid is hydroxylated by a member of the cytochrome P450 enzyme family.
  • This hydroxylated fatty acid is then converted into an aldehyde by an alcohol dehydrogenase, and subsequently this aldehyde is converted into a carboxyl group by an aldehyde dehydrogenase.
  • the final product of the pathway is a dicarboxylic fatty acid, which can be degraded further by oxidation from the ⁇ -end.
  • Oxidation from the ⁇ -end (“ ⁇ -oxidation”) is believed to be the main pathway for degradation of the fatty acid analogues as described with a block in the X position.
  • R' was changed to block ⁇ -oxidation, by introducing a triple bond at the methyl end of the fatty acid analogue.
  • This is important for the use of the fatty acid analogues in pharmaceutical preparation, as it may potentiate the effects of the ⁇ -oxidizable fatty acid analogues by further slowing down their breakdown.
  • R' methyl/hydrophobic head group end of the molecule
  • R' may be substituted in one or several positions with heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a CH 2 group, a SO group and a SO 2 group.
  • R' may also be substituted with one or more compounds selected from the group comprising fluoride, chloride, hydroxy, Ci- C 4 alkoxy, Ci-C 4 alkylthio, C 2 -C 5 acyloxy or Ci-C 4 alkyl.
  • the compounds according to the present invention are either fatty acids analogous to naturally occurring fatty acids, which are not capable of being ⁇ - oxidized, or naturally occurring lipids comprising said fatty acid analogues.
  • the fatty acid analogues show a strong preference for being incorporated into phospholipids.
  • a complex by including a fatty acid(s) which are not capable of being ⁇ -oxidized into a triacylglycerol.
  • Such compounds are encompassed by formulas (I) and (II). If such a triacylglycerol was taken orally, for instance in an animal feed product, it would probably be transported like any triacylglycerol, from the small intestine in chylomicrons and from the liver in the blood in lipoproteins to be stored in the adipose tissue or used by muscles, heart or the liver, by hydrolyzes of the triacylglycerol into glycerol and 3 free fatty acids. The free fatty acids would at this point be the parent compound of the present invention, and not a complex anymore.
  • glycerophospholipid derivatives of the fatty acids of the present invention includes, but are not limited to, phosphatidyl cholines, phosphatidyl ethanolamines, phosphatidyl inositols, phosphatidyl serines and phosphatidyl glycerols.
  • Another esterification of fatty acids found in vivo which could be easily used to make a complex for a compound of the present invention would be to make the alcohol or polyalcohol corresponding to the fatty acid, for example one could make a sphingolipid derivative such as ceramide or sphingomyelin by making the corresponding amino alcohol.
  • a sphingolipid derivative such as ceramide or sphingomyelin
  • glycerophospholipid complexes such complexes would be very water insoluble and less hydrophilic.
  • polar complexes of the present invention may be, but are not limited to, lysophospholipids, phosphatidic acis, alkoxy compounds, glycerocarbohydrates, gangliosiedes, and cerebrosides.
  • X is a sulphur atom
  • the thio-substituted compound used according to the present invention may be prepared by the general procedure indicated below:
  • TTA tetradecylthioaceticacid
  • X is a selenium atom: the seleno-substituted compound used according to the present invention may be prepared by the following general procedure
  • This compound was purified by carefully crystallisation from ethanol or methanol.
  • the dose level of 500 mg/kg/day also elicited body weight loss. There was no evidence of toxicity at dose levels of 50 or 500 mg/day/kg.
  • TTA and TSA did not induce mutations in strains of Salmonella typhimurium and Escherichia coli. Furthermore, TTA was not mutagenic when tested in mouse lymphoma cells and L5178Y.
  • TSA and TSA were found not to be mutagenic in these tests.
  • TSA and TTA have been tested for chromosomal aberrations in cultured Chinese hamster ovary cells and no aberrations were induced by the doses tested (12-140 mg/ml).
  • the compounds of the present invention are therefore potentially useful as pharmaceutical or nutritional compounds in this respect.
  • the total effective amount of the compounds according to the invention administered in the feed will preferably be in the range of about 1 mg/kg/day to 2g/kg/day of total body weight.
  • a dose of 5 - 500 mg/kg/day is preferable, while a dose of 50-100 mg/kg/day is most preferable.
  • the amount of compounds according to the invention present in the feed should be between 0.005 % and 5 % of the total weight of the feed, preferably between 0.05 % and 1 %, more preferably between 0.1 % and 0.5 %, most preferably 0.5 % of the total weight of the feed.
  • the feed may contain any amount of fat common in fish feed. But the feed should preferably be optimized by being energy rich, that is, it should preferably comprise fairly high levels of fat, at least 15 % by weight, preferably 15 % - 45 %, more preferably 20 % - 40 % fat by weight. The exact preference will of course vary with different fish species. However, a high fat content is not required for the compounds according to the invention to work, but it will most likely enhance their effect.
  • the given daily amounts should of course be the total daily amounts in the total feed consumed, and the percentages of the compounds according to the invention and the percentages of fats should also be for the total amounts of feed.
  • the percentages by weight of both compounds according to the invention and fats may greatly exceed the percentages given above, up to a feed comprised entirely of fats (therein included the compounds according to the invention).
  • the feed is used as a supplementary feed in addition to another feed(s), it may be administered to the fish separately from said another feed(s), or at the same time, or mixed with said another feed(s), as an example any conventional feed can be sprayed or soaked with a mixture of fat (preferably in liquid form) and a compound according to the invention, to thus obtain a feed according to the present invention.
  • baseline intake when used in regard to energy intake, refers to the intake of energy from food that the fish experience during normal growth, that is, when the fish is not subject to any extraneous stresses, such as an abrupt change of/in the environment, exposure to disease etc.
  • feed is used to describe any food fed to animals, comprising any fodder or specialty or supplemental feed or feed additive. Any feed can be supplemented with the composition of the present invention, to attain the biological effects thereof, and this is intended to be included in the definition of feed.
  • prodrug is commonly used in the art to describe a medicament which has been modified so that it has no effect in vitro, but is activated in vivo. Usually this modification is the addition of some compound to the parent drug, which the natural mechanisms in the body will remove, yielding the now active (original) parent drug. Thus such a “prodrug” is, biologically speaking, identical in its effects to the parent compound and the inclusion of the word “prodrug” in the compound descriptions does not widen the scope of compounds included in the patent.
  • Example 1 Reduction of IPN mortality in 1+ Atlantic salmon smolt after sea transfer in spring by potentially energy enhancing additives
  • One third of the smolt was vaccinated with Norvax Compact 4 (Aeromonas salmonicida susp. Salmonicida, Vibrio salmonicida, Vibrio Anguillarum serovar O1 and 02) and two third with Norvax Compact 6 Aeromonas salmonicida susp. Salmonicida, Vibrio salmonicida, Vibrio Anguillarum serovar 01 and 02, Vibrio viscosus and a surface protein from IPNV). Intervet Norbio AS delivered both vaccines.
  • the four different seawater diets were: S1 , a low fat control diet with 20% fat; S2, a high fat control diet with 29% fat; S3, the high fat control diet added 0.5% TTA and finally S4, the high fat control where 14.8% of the fat was substituted by MCT (Table 2).
  • RPS 100% x (1- % mortality in a given dietary group / % mortality in the control group)
  • Example 2 Increase in ⁇ -oxidation in muscle of salmon fed a diet containing TTA during the critical period following sea transfer.
  • Example 2 is part of a larger ongoing experiment with Atlantic salmon 1+ smolt hatched in January 2005 (Marine Harvest, Sl ⁇ rdal). On May 19 tn the fish were transferred to AKVAFORSK seawater research station at Aver ⁇ y on the west coast of Norway. On arrival to the sea site the fish were distributed in net pens with about 1100 fish in each. Mean body weight of the smolt was 104 grams at transfer. The part of the experiment described in this experiment focuses on two different diets fed in triplicates. Seawater temperature at transfer was 9.2°C increasing to 12.3 0 C at the end of the six weeks period with an average of 10.5 0 C.
  • the two different diets were: control diet and a diet added 0.5% TTA (Table 3), which is the same amount as in the feed fed in study 1.
  • the fish were fed for six-nine weeks, straight after transfer to seawater, until sampling for beta-oxidation and fat content in muscle, respectively.
  • the increased access to energy explain the observation of significantly lower levels of plasma chloride and hence reduced osmotic stress in smolt fed TTA compared to the control six weeks after sea transfer, two weeks prior to the outbreak of the disease. During this critical, but temporary, high metabolic energy-requiring period of 1 + smolt after sea transfer dietary addition of TTA increase significantly the ability of salmon smolt to resist IPN.
  • the inventors believe that the energy requirement of fish during critical and stressful periods is higher than can be obtained through the energy content in traditional feed, reducing growth and feed conversion, and acting as a predisposing factor for outbreak of diseases.
  • This increase in the requirements for energy of fish can be detected by the reduction in body lipid/energy stores and/or as the need of energy intake above the baseline intake.
  • Adding a compound according to the invention to feed during the critical and temporary high metabolic energy-requiring period of 1+ smolt after sea transfer thus increase the ability of salmon smolt to resist IPN virus infection.
  • Compounds according to the present invention should have a beneficial effect on any farmed fish during any temporary high metabolic energy-requiring period.
  • the compounds according to the present invention are known to increase ⁇ -oxidation, and may thus help to supply extra energy in any time periods where the requirements for energy of said fish is increased.
  • Such critical temporary high energy-requiring periods may comprise any time periods where the fish is subjected to unusual stress. This comprises time periods when fish is subjected to infections, comprising bacterial, viral or fungal infections, including but not limited to IPN infections, furunculosis, Pancreas dieseas (PD), HSMB (heart and skeletal muscle infection) and CMS (Cardiac Myopathy Syndrome). During such time periods the fish is in need of extra energy to fight off the infection, to lessen both the symptoms and/or mortality caused thereby.
  • infections comprising bacterial, viral or fungal infections, including but not limited to IPN infections, furunculosis, Pancreas dieseas (PD), HSMB (heart and skeletal muscle infection) and CMS (Cardiac Myopathy Syndrome).
  • These critical temporary time periods where the requirements for energy of said fish is increased also comprises transfer of fish to a new environment, including sea- transfer of fish, as well as transferral of hatchery reared fish to fresh or brackish water, or transferral from indoor tanks to the outdoors, or from one outdoor environment to a different environment, during any time of the year.
  • transferral to a new environment the fish must undergo a process of adaptation, whereupon the fish must expend energy, and thus the fish may need more energy than it can utilize from normal feed. If such extra energy is not provided, the fish may be more susceptible to disease, and to reduced growth and health in general.
  • the need for extra energy does not follow immediately after the transferral to a new environment, for instance the first spring spent in the sea after fall release of smolt from hatchery is a very critical time period, where the fish is susceptible to infections, in particular PD infections.
  • a feed in accordance with the invention would then be of great benefit to the health of the fish, providing extra energy needed to avoid or lessen the effects of infection.
  • these temporary time periods where the requirements for energy of said fish is increased also comprises time periods when the fish is not transferred to a new environment, but rather when their environment is changing.
  • An example would be a particularly cold winter, especially with water temperatures at 5°C or lower, or very sudden changes in the environment that would cause the fish undue stress.
  • a feed according to the invention would be highly beneficial.
  • Salmon is not the only type of farmed fish that is subject to critical temporary high energy-requiring periods where said fish is in need of exceeding the energy intake above the baseline intake. Any farmed fish could benefit from a feed according to the present invention tailored to their needs during such time periods.
  • the compounds according to the present invention have a basic effect on ⁇ -oxidation, and this should not be any different in other fish species.
  • the invention could be used for any farmed fish species, although preferred species comprise cod, charr, halibut and catfish, more preferred species comprise salmon and trout, and the most preferred species comprise Atlantic salmon, Coho salmon, rainbow trout and brown trout.
PCT/NO2006/000424 2005-11-23 2006-11-22 Use of fatty acid analogues WO2007061314A2 (en)

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