Efficacy and safety of dietary supplements containing CLA for the treatment of obesity
2003; Elsevier BV; Volume: 44; Issue: 12 Linguagem: Inglês
10.1194/jlr.r300011-jlr200
ISSN1539-7262
AutoresThomas M. Larsen, S Toubro, Arne Astrup,
Tópico(s)Lipid metabolism and biosynthesis
ResumoDietary supplements containing conjugated linoleic acid (CLA) are widely promoted as weight loss agents available over the counter and via the Internet. In this review, we evaluate the efficacy and safety of CLA supplementation based on peer-reviewed published results from randomized, placebo-controlled, human intervention trials lasting more than 4 weeks. We also review findings from experimental studies in animals and studies performed in vitro. CLA appears to produce loss of fat mass and increase of lean tissue mass in rodents, but the results from 13 randomized, controlled, short-term (<6 months) trials in humans find little evidence to support that CLA reduces body weight or promotes repartitioning of body fat and fat-free mass in man. However, there is increasing evidence from mice and human studies that the CLA isomer trans-10, cis-12 may produce liver hypertrophy and insulin resistance via a redistribution of fat deposition that resembles lipodystrophy. CLA also decreases the fat content of both human and bovine milk.In conclusion, although CLA appears to attenuate increases in body weight and body fat in several animal models, CLA isomers sold as dietary supplements are not effective as weight loss agents in humans and may actually have adverse effects on human health. Dietary supplements containing conjugated linoleic acid (CLA) are widely promoted as weight loss agents available over the counter and via the Internet. In this review, we evaluate the efficacy and safety of CLA supplementation based on peer-reviewed published results from randomized, placebo-controlled, human intervention trials lasting more than 4 weeks. We also review findings from experimental studies in animals and studies performed in vitro. CLA appears to produce loss of fat mass and increase of lean tissue mass in rodents, but the results from 13 randomized, controlled, short-term ( 90%) is c9,t11. The amount of CLA present in dairy products varies according to the animal breed and the processing of the product, but the major determinant appears to be livestock feeding conditions (3Lawson R.E. Moss A.R. G.DI. The role of dairy products in supplying conjugated linoleic acid to man's diet: a review.Nutr. Res. Rev. 2002; 14: 153-172Crossref Scopus (143) Google Scholar, 4Bauman D.E. Griinari J.M. Regulation and nutritional manipulation of milk fat: low-fat milk syndrome.Livest. Prod. Sci. 2000; 70: 15-29Abstract Full Text Full Text PDF Scopus (468) Google Scholar). Various livestock feeding strategies have been used for increasing the CLA content of cow's milk. Data on CLA content of animal food products have recently become available, allowing estimation of human intakes. Recent studies suggest average intakes of ∼150–200 mg/day (5Jiang J. Wolk A. Vessby B. Relation between the intake of milk fat and the occurrence of conjugated linoleic acid in human adipose tissue.Am. J. Clin. 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In comparison, CLA dietary supplements marketed for weight loss purposes constitute an intake of 3–4 g/day (8Pharma Nord ApS Denmark Bio-C.L.A. 80.http://www.pharmanord.dk/product.htm?l=dk&id=claDate: 2002Date accessed: November 27, 2003Google Scholar). Dietary CLA is recovered in human milk, serum lipids, and in adipose tissue. A significant correlation between the proportion of c9,t11 CLA in adipose tissue and milk fat intake has been found, and c9,t11 CLA can comprise 0.5% by weight of total fatty acids in human adipose tissue (5Jiang J. Wolk A. Vessby B. Relation between the intake of milk fat and the occurrence of conjugated linoleic acid in human adipose tissue.Am. J. Clin. Nutr. 1999; 70: 21-27Crossref PubMed Scopus (120) Google Scholar). CLA has been studied extensively in various animal species, and in general, it is now widely recognized that feeding CLA (various mixtures of isomers) to different animals (including mice, hamsters, rats, chickens, and dogs) results in changes in body composition, i.e., lowering of body weight and fat mass (FM) and a relative increase in lean body mass [as reviewed in ref. (9Roche H.M. Noone E. Nugent A. Gibney M.J. Conjugated linoleic acid: a novel therapeutic nutrient?.Nutr. Res. Rev. 2001; 14: 173-187Crossref PubMed Scopus (120) Google Scholar)]. For example, 6 weeks' administration of CLA (1% CLA added by weight to a low-fat diet, ∼1.5g CLA/kg body weight) has been shown to decrease body weight by ∼10% and body fat by ∼70% when compared with placebo in mice (10West D.B. Delany J.P. Camet P.M. Blohm F. Truett A.A. Scimeca J. Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse.Am. J. Physiol. 1998; 275: R667-R672PubMed Google Scholar). Furthermore, it has been shown, using accurate dual energy X-ray scanning methods, that CLA dose-dependently decreases fat accretion in growing pigs (11Ostrowska E. Suster D. Muralitharan M. Cross R.F. Leury B.J. Bauman D.E. Dunshea F.R. Conjugated linoleic acid decreases fat accretion in pigs: evaluation by dual-energy X-ray absorptiometry.Br. J. Nutr. 2003; 89: 219-229Crossref PubMed Scopus (64) Google Scholar). It appears that the effects on body composition are largest when CLA is given to the animal during growth periods, but the effects also depend on several other factors, including species, age, gender, dosage, and duration of CLA feeding, but perhaps most importantly, the CLA isomer composition. In the majority of the animal studies performed, the CLA preparations used have been mixtures of CLA isomers, i.e., usually a mixture composed of 30–40% of each of the c9,t11 and t10,c12 isomers, the residue consisting of various less-common isomers. Although CLA has effects when given as a mixture, recent studies in mice and hamsters have identified the t10,c12 isomer, rather than the c9,t11 isomer, as being responsible for the attenuation of body weight gain and for the reduction of body fat (12Park Y. Storkson J.M. Albright K.J. Liu W. Pariza M.W. Evidence that the trans-10,cis-12 isomer of conjugated linoleic acid induces body composition changes in mice.Lipids. 1999; 34: 235-241Crossref PubMed Scopus (691) Google Scholar, 13Gavino V.C. Gavino G. Leblanc M.J. Tuchweber B. An isomeric mixture of conjugated linoleic acids but not pure cis-9, trans-11-octadecadienoic acid affects body weight gain and plasma lipids in hamsters.J. Nutr. 2000; 130: 27-29Crossref PubMed Scopus (167) Google Scholar). In a study on Zucker Diabetic Fatty (ZDF) rats, c9,t11 CLA had no significant effects, whereas a mixture of c9,t11 and t10,c12 lowered body weight, although this was partly a result of a decreased energy intake (14Ryder J.W. Portocarrero C.P. Song X.M. Cui L. Yu M. Combatsiaris T. Galuska D. Bauman D.E. Barbano D.M. Charron M.J. Zierath J.R. Houseknecht K.L. Isomer-specific antidiabetic properties of conjugated linoleic acid. Improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression.Diabetes. 2001; 50: 1149-1157Crossref PubMed Scopus (274) Google Scholar). In general, the CLA-induced changes in cardiovascular risk factors, glucose tolerance, blood levels of free fatty acids, triglycerides, total-, LDL-, HDL- and/or VLDL-cholesterol, and liver metabolism observed in the various animal studies are conflicting. There is considerable evidence that feeding CLA may affect liver metabolism and have adverse effects on glucose homeostasis in mice. Early studies in mice found that CLA induces peroxisome proliferation in the liver (15Belury M.A. Moya-Camarena S.Y. Liu K.L. Vanden Heuvel J.P. Dietary conjugated linoleic acid induces peroxisome-specific enzyme accumulation and ornithine decarboxylase activity in mouse liver.J. Nutr. Biochem. 1997; 8: 579-584Crossref Scopus (113) Google Scholar). In mice and chickens, CLA supplementation has been associated with increases in liver weight, possibly as a result of triglyceride accumulation (16DeLany J.P. Blohm F. Truett A.A. Scimeca J.A. West D.B. Conjugated linoleic acid rapidly reduces body fat content in mice without affecting energy intake.Am. J. Physiol. 1999; 276: R1172-R1179PubMed Google Scholar, 17Belury M.A. Kempa-Steczko A. Conjugated linoleic acid modulates hepatic lipid composition in mice.Lipids. 1997; 32: 199-204Crossref PubMed Scopus (305) Google Scholar, 18Cherian G. Holsonbake T.B. Goeger M.P. Bildfell R. Dietary CLA alters yolk and tissue FA composition and hepatic histopathology of laying hens.Lipids. 2002; 37: 751-757Crossref PubMed Scopus (46) Google Scholar). In hamsters, the t10,c12 isomer causes enlargement of both liver and kidney, despite a lower body weight (19de Deckere E.A. van Amelsvoort J.M. McNeill G.P. Jones P. Effects of conjugated linoleic acid (CLA) isomers on lipid levels and peroxisome proliferation in the hamster.Br. J. Nutr. 1999; 82: 309-317Crossref PubMed Google Scholar). In rats, however, CLA does not act as a classic peroxisome proliferator, despite moderate increases in liver weight (20Yamasaki M. Mansho K. Mishima H. Kimura G. Sasaki M. Kasai M. Tachibana H. Yamada K. Effect of dietary conjugated linoleic acid on lipid peroxidation and histological change in rat liver tissues.J. Agric. Food Chem. 2000; 48: 6367-6371Crossref PubMed Scopus (32) Google Scholar, 21Jones P.A. Lea L.J. Pendlington R.U. Investigation of the potential of conjugated linoleic acid (Cla) to cause peroxisome proliferation in rats.Food Chem. Toxicol. 1999; 37: 1119-1125Crossref PubMed Scopus (16) Google Scholar, 22Moya-Camarena S.Y. Van den Heuvel J.P. Belury M.A. Conjugated linoleic acid activates peroxisome proliferator-activated receptor alpha and beta subtypes but does not induce hepatic peroxisome proliferation in Sprague-Dawley rats.Biochim. Biophys. Acta. 1999; 1436: 331-342Crossref PubMed Scopus (147) Google Scholar). Positive findings awakened interest in the health benefits of CLA. It was found that feeding rabbits a CLA mixture caused a substantial regression of established atherosclerosis, despite a significant increase in serum total cholesterol and decrease in HDL-cholesterol (23Kritchevsky D. Tepper S.A. Wright S. Tso P. Czarnecki S.K. Influence of conjugated linoleic acid (CLA) on establishment and progression of atherosclerosis in rabbits.J. Am. Coll. Nutr. 2000; 19: 472-477Crossref Scopus (238) Google Scholar). However, others have found an increase in arterial fatty streak formation in c57BL/6 mice after CLA supplementation (24Munday J.S. Thompson K.G. James K.A. 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Houseknecht K.L. Isomer-specific antidiabetic properties of conjugated linoleic acid. Improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression.Diabetes. 2001; 50: 1149-1157Crossref PubMed Scopus (274) Google Scholar, 26Henriksen E.J. Teachey M.K. Taylor Z.C. Jacob S. Ptock A. Kramer K. Hasselwander O. Isomer-specific actions of conjugated linoleic acid on muscle glucose transport in the obese Zucker rat.Am. J. Physiol. Endocrinol. Metab. 2003; 285: E98-E105Crossref PubMed Scopus (80) Google Scholar). In contrast, CLA supplementation has been found to increase serum insulin levels in rats (27McCarthy-Beckett D.O. Dietary supplementation with conjugated linoleic acid does not improve nutritional status of tumor-bearing rats.Res. Nurs. Health. 2002; 25: 49-57Crossref PubMed Scopus (10) Google Scholar). In mice and hamsters, CLA supplementation has been associated with increases in plasma insulin levels (10West D.B. Delany J.P. Camet P.M. Blohm F. Truett A.A. Scimeca J. Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse.Am. J. Physiol. 1998; 275: R667-R672PubMed Google Scholar, 28Bouthegourd J.C. Even P.C. Gripois D. Tiffon B. Blouquit M.F. Roseau S. Lutton C. Tome D. Martin J.C. A CLA mixture prevents body triglyceride accumulation without affecting energy expenditure in Syrian hamsters.J. Nutr. 2002; 132: 2682-2689Crossref PubMed Scopus (61) Google Scholar). Similarly, despite resulting in decreased body weight, t10,c12 supplementation in mice was associated with increased serum glucose and insulin levels, whereas the c9,t11 supplementation group showed no weight loss, but lowered triglycerides and FFA (29Roche H.M. Noone E. Sewte C. McBennett S. Savage D. Gibney M.J. O'Rahilly S. Vidal-Puig A.J. Isomer-dependent metabolic effects of conjugated linoleic acid: insights from molecular markers sterol regulatory element-binding protein-1c and LXRalpha.Diabetes. 2002; 51: 2037-2044Crossref PubMed Scopus (158) Google Scholar). This study is in line with other studies in mice showing that CLA supplementation (36% t10,c12 isomer) results in marked reductions in body fat, although this was associated with the development of insulin resistance, resulting in a metabolic state resembling lipoatrophic diabetes (30Tsuboyama-Kasaoka N. Takahashi M. Tanemura K. Kim H.J. Tange T. Okuyama H. Kasai M. Ikemoto S. Ezaki O. Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice.Diabetes. 2000; 49: 1534-1542Crossref PubMed Scopus (488) Google Scholar, 31Tsuboyama-Kasaoka N. Miyazaki H. Kasaoka S. Ezaki O. Increasing the amount of fat in a conjugated linoleic acid-supplemented diet reduces lipodystrophy in mice.J. Nutr. 2003; 133: 1793-1799Crossref PubMed Scopus (67) Google Scholar). Similar observations have been reported by other researchers, showing that mice fed purified t10,c12 CLA or CLA mixtures develop hyperinsulinemia and fatty liver (29Roche H.M. Noone E. Sewte C. McBennett S. Savage D. Gibney M.J. O'Rahilly S. Vidal-Puig A.J. Isomer-dependent metabolic effects of conjugated linoleic acid: insights from molecular markers sterol regulatory element-binding protein-1c and LXRalpha.Diabetes. 2002; 51: 2037-2044Crossref PubMed Scopus (158) Google Scholar, 32Clement L. Poirier H. Niot I. Bocher V. Guerre-Millo M. Krief S. Staels B. Besnard P. Dietary trans-10,cis-12 conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse.J. Lipid Res. 2002; 43: 1400-1409Abstract Full Text Full Text PDF PubMed Scopus (299) Google Scholar, 33Degrace P. Demizieux L. Gresti J. Chardigny J.M. Sebedio J.L. Clouet P. 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Ezaki O. Increasing the amount of fat in a conjugated linoleic acid-supplemented diet reduces lipodystrophy in mice.J. Nutr. 2003; 133: 1793-1799Crossref PubMed Scopus (67) Google Scholar). There is accumulating evidence that CLA may regulate lipid metabolism in addition to its effects on body composition per se. The t10,c12 isomer has been shown to inhibit the transcription and activity of stearoyl-CoA desaturase 1 (SCD1) in porcine adipose tissue in ex vivo studies (35Smith S.B. Hively T.S. Cortese G.M. Han J.J. Chung K.Y. Castenada P. Gilbert C.D. Adams V.L. Mersmann H.J. Conjugated linoleic acid depresses the delta9 desaturase index and stearoyl coenzyme A desaturase enzyme activity in porcine subcutaneous adipose tissue.J. Anim. Sci. 2002; 80: 2110-2115Crossref PubMed Google Scholar). SCD1 desaturates saturated fatty acids (SFAs) into monounsaturated fatty acids (MUFAs), resulting in a higher δ-9 desaturase index, i.e., a higher MUFA/SFA ratio. In vitro studies have also delineated isomer-specific effects on SCD1 activity. The t10,c12 isomer seems to inhibit the expression of SCD1 mRNA in liver cells from mice fed the isomer and in mice liver cell lines, leading to decreased C16:1/C16:0 and C18:1/C18:0 ratios (36Lee K.N. Pariza M.W. Ntambi J.M. Conjugated linoleic acid decreases hepatic stearoyl-CoA desaturase mRNA expression.Biochem. Biophys. Res. Commun. 1998; 248: 817-821Crossref PubMed Scopus (242) Google Scholar). Similarly, t10,c12 decreased SCD1 mRNA expression and activity in 3T3-L1 adipocytes, and resulted in cells with smaller lipid droplets (37Choi Y. Kim Y.C. Han Y.B. Park Y. Pariza M.W. Ntambi J.M. The trans-10,cis-12 isomer of conjugated linoleic acid downregulates stearoyl-CoA desaturase 1 gene expression in 3T3–L1 adipocytes.J. Nutr. 2000; 130: 1920-1924Crossref PubMed Scopus (252) Google Scholar). This modulation of the ratio of MUFA/SFA (presumably by the t10,c12 isomer) has also been observed in milk fat from cows fed t10,c12 supplements (38Baumgard L.H. Corl B.A. Dwyer D.A. Saebo A. Bauman D.E. Identification of the conjugated linoleic acid isomer that inhibits milk fat synthesis.Am. J. Physiol. Regul. Integr. Comp. Physiol. 2000; 278: R179-R184Crossref PubMed Google Scholar, 39Baumgard L.H. Matitashvili E. Corl B.A. Dwyer D.A. Bauman D.E. Trans-10, cis-12 conjugated linoleic acid decreases lipogenic rates and expression of genes involved in milk lipid synthesis in dairy cows.J. Dairy Sci. 2002; 85: 2155-2163Abstract Full Text Full Text PDF PubMed Scopus (287) Google Scholar). In addition, the t10,c12 isomer seems to be responsible for the reduced milk fat production observed in cows, also known as milk fat depression syndrome, which occurs when cows are fed diets containing large amounts of unsaturated oils, such as plant and fish oils (4Bauman D.E. Griinari J.M. Regulation and nutritional manipulation of milk fat: low-fat milk syndrome.Livest. Prod. Sci. 2000; 70: 15-29Abstract Full Text Full Text PDF Scopus (468) Google Scholar). Hence, in cows fed either a purified t10,c12 diet or a known milk fat-depressing diet, the de novo fatty acid synthesis and/or the utilization of circulating fatty acids is severely inhibited, resulting in a markedly lower milk fat production (40Piperova L.S. Teter B.B. Bruckental I. Sampugna J. Mills S.E. Yurawecz M.P. Fritsche J. Ku K. Erdman R.A. Mammary lipogenic enzyme activity, trans fatty acids and conjugated linoleic acids are altered in lactating dairy cows fed a milk fat-depressing diet.J. Nutr. 2000; 130: 2568-2574Crossref PubMed Scopus (213) Google Scholar, 41Peterson D.G. Baumgard L.H. Bauman D.E. Short communication: milk fat response to low doses of tran-10, cis-12 conjugated linoleic acid (CLA).J. 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It has also been observed recently that CLA supplements may decrease mammary milk fat production in several other animal models, including mice, pigs, (43Bee G. Dietary conjugated linoleic acid consumption during pregnancy and lactation influences growth and tissue composition in weaned pigs.J. Nutr. 2000; 130: 2981-2989Crossref PubMed Scopus (66) Google Scholar) and humans (44Masters N. McGuire M.A. Beerman K.A. Dasgupta N. McGuire M.K. Maternal supplementation with CLA decreases milk fat in humans.Lipids. 2002; 37: 133-138Crossref PubMed Scopus (69) Google Scholar). Early studies found that CLA significantly reduced the density of the branching mammary epithelium in rats (45Thompson H. Zhu Z. Banni S. Darcy K. Loftus T. Ip C. Morphological and biochemical status of the mammary gland as influenced by conjugated linoleic acid: implication for a reduction in mammary cancer risk.Cancer Res. 1997; 57: 5067-5072PubMed Google Scholar). This decrease in milk fat content may influence the growth of the offspring. It has been reported that dietary CLA decreases yolk 18:1(n-9) and increases SFA content (46Raes K. Huyghebaert G. De Smet S. Nollet L. Arnouts S. Demeyer D. The deposition of conjugated linoleic acids in eggs of laying hens fed diets varying in fat level and fatty acid profile.J. Nutr. 2002; 132: 182-189Crossref PubMed Scopus (90) Google Scholar) in hens' eggs, causing yolk hardening and inducing chick embryonic mortality (47Aydin R. Pariza M.W. Cook M.E. Olive oil prevents the adverse effects of dietary conjugated linoleic acid on chick hatchability and egg quality.J. Nutr. 2001; 131: 800-806Crossref PubMed Scopus (80) Google Scholar). However, in rats, no effects on litter growth were seen when lactating rats were fed t10,c12 CLA. Mice with a targeted disruption of the gene encoding SCD1, shown to be resistant to diet-induced weight gain, had increased lipid oxidation and plasma levels of ketone bodies, and reduced levels of plasma insulin and leptin, but developed signs of hepatic steatosis when fed a high-fat diet (48Ntambi J.M. Miyazaki M. Stoehr J.P. Lan H. Kendziorski C.M. Yandell B.S. Song Y. Cohen P. Friedman J.M. Attie A.D. Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity.Proc. Natl. Acad. Sci. USA. 2002; 99: 11482-11486Crossref PubMed Scopus (880) Google Scholar). In summary, although CLA-induced decreases of the MUFA/SFA ratio seem to be involved in the general inhibition of adipogenesis, we do not yet know exactly how this may otherwise influence health in animals and humans. The mechanism of action of the peripheral body fat-decreasing effect of CLA has not yet been fully elucidated. CLA does not seem to enhance energy expenditure acutely, but has been shown to increase energy expenditure in mice fed CLA for 6 weeks, despite a significant weight loss (10West D.B. Delany J.P. Camet P.M. Blohm F. Truett A.A. Scimeca J. Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse.Am. J. Physiol. 1998; 275: R667-R672PubMed Google Scholar, 49West D.B. Blohm F.Y. Truett A.A. DeLany J.P. Conjugated linoleic acid persistently increases total energy expenditure in AKR/J mice without increasing uncoupling protein gene expression.J. Nutr. 2000; 130: 2471-2477Crossref PubMed Scopus (161) Google Scholar). There is also controversy as to whether CLA affects energy intake, and some studies suggest that CLA may induce feeding aversion in mice (10West D.B. Delany J.P. Camet P.M. Blohm F. Truett A.A. Scimeca J. Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse.Am. J. Physiol. 1998; 275: R667-R672PubMed Google Scholar) and rats (14Ryder J.W. Portocarrero C.P. Song X.M. Cui L. Yu M. Combatsiaris T. Galuska D. Bauman D.E. Barbano D.M. Charron M.J. Zierath J.R. Houseknecht K.L. Isomer-specific antidiabetic properties of conjugated linoleic acid. Improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression.Diabetes. 2001; 50: 1149-1157Crossref PubMed Scopus (274) Google Scholar); yet CLA seems to have effects on body composition in mice independent of changes in energy intake (50Hargrave K.M. Li C. Meyer B.J. Kachman S.D. Hartzell D.L. Della-Fera M.A. Miner J.L. Baile C.A. Adipose depletion and apoptosis induced by trans-10, cis-12 conjugated linoleic acid in mice.Obes. Res. 2002; 10: 1284-1290Crossref PubMed Scopus (85) Google Scholar). Despite these suggestions that an increased energy expenditure and a decreased energy intake occur with CLA intake, most of the evidence suggests that the major part of the effect on body fat changes can be explained by the attenuation of fat cell differentiation by the t10,c12 isomer. In vitro studies of primary cultures of stromal vascular cells from human adipose tissue have shown that t10,c12 can lower triglyceride incorporation in these cells (i.e., inhibit lipogenesis), whereas the c9,t11 isomer increases the triglyceride content (51Brown J.M. Halvorsen Y.D. Lea-Currie Y.R. Geigerman C. McIntosh M. Trans-10, cis-12, but not cis-9, trans-11, conjugated linoleic acid attenuates lipogenesis in primary cultures of stromal vascular cells from human adipose tissue.J. Nutr. 2001; 131: 2316-2321Crossref PubMed Scopus (124) Google Scholar, 52Brown J.M. Boysen M.S. Jensen S.S. Morrison R.F. Storkson J. Lea-Currie R. Pariza M. Mandrup S. McIntosh M.K. Isomer-specific regulation of metabolism and PPAR{gamma} signaling by CLA in human preadipocytes.J. Lipid Res. 2003; 44: 1287-1300Abstract Full Text Full Text PDF PubMed Scopus (198) Google Scholar). Similarly, the t10,c12 isomer has consistently been shown to decrease the differentiation of 3T3-L1 adipocytes, possibly via a decrease in the expression and/or activation of the peroxisome proliferator-activated receptor γ, which is a strong inducer of adipocyte differentiation (53Kang K. Liu W. Albright K.J. Park Y. Pariza M.W. Trans-10,cis-12 CLA inhibits differentiation of 3T3-L1 adipocytes and decreases PPAR gamma expression.Biochem. Biophys. Res. Commun. 2003; 303: 795-799Crossref PubMed Scopus (143) Google Scholar, 54Granlund L. Juvet L.K. Pedersen J.I. Nebb H.I. Trans10, cis12 conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPARgamma modulator.J. Lipid Res. 2003; 44: 1441
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