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

Brown, J. Mark; Halvorsen, Yuan Di C.; Lea-Currie, Y. Renee; Geigerman, Cissy; McIntosh, M. K.

doi:10.1093/jn/131.9.2316

Cited by 122 publications

(125 citation statements)

References 22 publications

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“…A reduced intracellular TAG content in mature 3T3-L1 adipocytes was found to be due to the t 10, c 12 isomer (24,28). This also has been observed in primary cultures of stromal vascular cells from human adipose tissue (30).…”

supporting

confidence: 61%

Trans10, cis12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPARγ modulator

Granlund

Juvet

Pedersen

et al. 2003

Journal of Lipid Research

108

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A group of polyunsaturated fatty acids called conjugated linoleic acids (CLAs) are found in ruminant products, where the most common isomers are cis 9, trans 11 ( c 9, t 11) and trans 10, cis 12 ( t 10, c 12) CLA. A crude mixture of these isomers has been shown in animal studies to alter body composition by a reduction in body fat mass as well as an increase in lean body mass, with the t 10, c 12 isomer having the most pronounced effect. The objective of this study was to establish the molecular mechanisms by which t 10, c 12 CLA affects lipid accumulation in adipocytes. We have shown that t 10, c 12 CLA prevents lipid accumulation in human and mouse adipocytes at concentrations as low as 5 M and 25 M, respectively. Adipocytes play a central role in maintaining lipid homeostasis and energy balance in vertebrates by storing triacylglycerols (TAGs) or releasing free fatty acids in response to changes in energy demands (1). The increase in incidence of obesity and Type II diabetes has focused attention on all aspects of adipocyte biology (2). In this regard, transcription factors have been identified that directly influence adipogenesis, in which peroxisome proliferatoractivated receptor ␥ (PPAR ␥ ) has been shown to play a crucial role (3).PPAR ␥ is a member of the nuclear hormone receptor super family (4), which forms heterodimers with the retinoid X receptor (RXR), and regulates gene expression by binding to a PPAR-responsive element (PPRE) of the direct repeat 1 type in the promoter region of a variety of target genes (5, 6). PPAR ␥ 2 is found almost exclusively in adipose tissue and has been linked to adipocyte differentiation (7,8). Natural high-affinity ligands for PPAR ␥ have not been identified, but polyunsaturated fatty acids and 15-deoxy-12,14-prostaglandin J2 show micromolar affinity for the receptor, in line with their serum levels (9, 10). Interest in the PPAR ␥ receptor field increased when a new class of synthetic antidiabetic drugs, the thiazolidinediones (TZDs), were shown to act as high-affinity ligands for PPAR ␥ (4). The effects of these ligands are mediated by changes in the transcriptional rate of PPAR ␥ target genes (11). Even though TZDs are used in the treatment of Type II diabetes, they are shown to induce adiposity and body weight gain in rodents (12) as well as weight gain in human patients (13). On the other hand, Mukherjee and coworkers have described a synthetic PPAR ␥ modulator, LG100641, which blocks adipocyte differentiation but stimulates glucose uptake in 3T3-L1 adipocytes (14).Conjugated linoleic acids (CLAs) are a group of positional and geometric isomers of linoleic acid (C18:2n-6), produced by bacterial biohydrogenation in the ruminant gut (15). The best sources for CLAs in the human diet are ruminant meat and dairy products (16,17), in which the two predominant isomers are cis 9, trans 11 ( c 9 ,t 11) and trans 10, cis 12 ( t 10, c 12) CLA. In rodents, a crude mixture of CLA isomers is shown to have anticarcinogenic (18), antiatherogenic (19,20), antidiabetic (21),...

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supporting

confidence: 61%

Trans10, cis12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPARγ modulator

Granlund

Juvet

Pedersen

et al. 2003

Journal of Lipid Research

108

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“…CLA inhibited fatty acid synthetase activity in rat liver. (Oku et al, 2003), and the t10,c12 isomer attenuated lipogenesis in human AT cells (Brown et al, 2001). Therefore, CLA can affect lipid accumulation both by decreasing synthesis and increasing oxidation.…”

Section: Discussionmentioning

confidence: 96%

Influence of dietary conjugated linoleic acid (CLA) on lipid and fatty acid composition in liver and flesh of Atlantic salmon (Salmo salar)

Kennedy

Campbell

Porter

et al. 2005

Comparative Biochemistry and Physiology Part B: Biochemistry an

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The aim of the present study was to determine the effects of conjugated linoleic acid (CLA) on lipid and fatty acid metabolism in Atlantic salmon. The overall objective being to test the hypotheses that CLA has beneficial effects in salmon including growth enhancement, improved flesh quality through decreased adiposity and lipid deposition thereby minimising detrimental effects of feeding high fat diets, and increased nutritional quality through increased levels of beneficial fatty acids including n-3 highly unsaturated fatty acids (HUFA) and CLA itself. Salmon smolts were fed diets containing two levels of fish oil (low, ~18% and high, ~34%) containing three levels of CLA (a 1:1 mixture of 9-cis,trans-11 and trans-10,cis-12. at 0, 1 and 2% of diet) for 3 months and the effects on growth performance, liver and muscle (flesh) lipid contents and class compositions, and fatty acid compositions determined. The diets were also specifically formulated to investigate whether the effects of CLA, if any, were more dependent upon absolute content of CLA in the diet (as percentage of total diet) or the relative level of CLA to other fatty acids. Dietary CLA in salmon smolts had no effect on growth parameters or biometric parameters. However, there was a clear trend of increased total lipid and triacylglycerol contents in both liver and flesh in fish fed CLA, particularly in fish fed the high oil diets. Finally, CLA was incorporated into tissue lipids, with levels in flesh being 2-fold higher than in liver, but importantly, incorporation in liver was at the expense of saturated and monounsaturated fatty acids whereas in flesh it was at the expense of n-3HUFA.3

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“…77 Supporting data have been reported by other studies using the cultures of human preadipocytes 48,78,79 and stromal vascular cells from human adipose tissue. 80 Data from the above studies collectively suggest that CLA decreases triglyceride content, in part, by decreasing fatty acid synthesis, uptake and esterification into triglyceride by adipocytes, at least in certain species and model systems.…”

Section: Conjugated Linoleic Acid and Obesitymentioning

confidence: 91%

Conjugated linoleic acid and obesity control: efficacy and mechanisms

2004

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Obesity is associated with high blood cholesterol and high risk for developing diabetes and cardiovascular disease. Therefore, management of body weight and obesity are increasingly considered as an important approach to maintaining healthy cholesterol profiles and reducing cardiovascular risk. The present review addresses the effects of conjugated linoleic acid (CLA) on fat deposition, body weight and composition, safety, as well as mechanisms involved in animals and humans. Animal studies have shown promising effects of CLA on body weight and fat deposition. The majority of the animal studies have been conducted using CLA mixtures that contained approximately equal amounts of trans-10, cis-12 (t10c12) and cis-9, trans-11 (c9t11) isomers. Results of a few studies in mice fed CLA mixtures with different ratios of c9t11 and t10c12 isomers have indicated that the t10c12 isomer CLA may be the active form of CLA affecting weight gain and fat deposition. Inductions of leptin reduction and insulin resistance are the adverse effects of CLA observed in only mice. In pigs, the effects of CLA on weight gain and fat deposition are inconsistent, and no adverse effects of CLA have been reported. A number of human studies suggest that CLA supplementation has no effect on body weight and insulin sensitivity. Although it is suggested that the t10c12 CLA is the antiadipogenic isomer of CLA in humans, the effects of CLA on fat deposition are marginal and more equivocal as compared to results observed in animal studies. Mechanisms through which CLA reduces body weight and fat deposition remain to be fully understood. Proposed antiobesity mechanisms of CLA include decreased energy/food intake and increased energy expenditure, decreased preadipocyte differentiation and proliferation, decreased lipogenesis, and increased lipolysis and fat oxidation. In summary, CLA reduces weight gain and fat deposition in rodents, while produces less significant and inconsistent effects on body weight and composition in pigs and humans. New studies are required to examine isomer-specific effects and mechanisms of CLA in animals and humans using purified individual CLA isomers.

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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

Cited by 122 publications

References 22 publications

Trans10, cis12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPARγ modulator

Trans10, cis12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPARγ modulator

Influence of dietary conjugated linoleic acid (CLA) on lipid and fatty acid composition in liver and flesh of Atlantic salmon (Salmo salar)

Conjugated linoleic acid and obesity control: efficacy and mechanisms

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