Antiobesity mechanisms of action of conjugated linoleic acid. J Nutr Biochem

Department of Nutrition, University of North Carolina Greensboro, PO Box 26170, Greensboro, NC 27402-6170, USA.
The Journal of nutritional biochemistry (Impact Factor: 3.79). 11/2009; 21(3):171-9. DOI: 10.1016/j.jnutbio.2009.08.003
Source: PubMed


Conjugated linoleic acid (CLA), a family of fatty acids found in beef, dairy foods and dietary supplements, reduces adiposity in several animal models of obesity and some human studies. However, the isomer-specific antiobesity mechanisms of action of CLA are unclear, and its use in humans is controversial. This review will summarize in vivo and in vitro findings from the literature regarding potential mechanisms by which CLA reduces adiposity, including its impact on (a) energy metabolism, (b) adipogenesis, (c) inflammation, (d) lipid metabolism and (e) apoptosis.

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Available from: Susanne Mandrup
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    • "The effects of CLA have been previously demonstrated as to influence on development of cancer and atherosclerosis, as well as preventing osteoporosis and modulating immune responses [5] [6]. Moreover, CLA has drawn special attention in the last two decades for its anti-obesity effect through various mechanisms, such as regulation of energy and lipid metabolism, adipogenesis, inflammation, and adipocyte apoptosis [7] [8]. In addition, it was reported that CLA improved voluntary activity and endurance capacity in animal models, including N2KO animals, and CLA modulated energy metabolism, especially uncoupling protein 2 (UCP2) and peroxisome proliferator-activated receptor d (PPARd) in skeletal muscle [9] [10]. "
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    ABSTRACT: Recently, conjugated linoleic acid (CLA) has been reported to prevent body weight gain and fat accumulation in part by improving physical activity in mice. The current study was conducted to determine the role of CLA on skeletal muscle metabolism in nescient basic helix-loop-helix 2 knock-out (N2KO) mice, an adult-onset inactivity induced obese model. Five-week-old female N2KO and wild type mice were fed either control or CLA containing diet (0.5%) for 10wk. Voluntary activity was determined biweekly and markers for muscle metabolisms were determined from the gastrocnemius muscle. CLA fed N2KO animals showed significant increased voluntary movement and gastrocnemius muscle mass compared to control group, whereas in wild type animals, no differences were observed. CLA treatment up-regulated AMP-activated protein kinase (AMPK), mitochondria biogenic markers, peroxisome proliferator-activated receptor-δ (PPARδ), and mitochondrial transcription factor A (Tfam) compared to control animals. These observations indicate that CLA supplementation activates AMPKα-PPARδ and/or -Tfam signaling cascade for stimulating mitochondria biogenesis. Taken together, these results suggest that CLA may in part activate the underlying biomarkers involved in muscle metabolism via stimulation of mitochondrial biogenesis, resulting in increased voluntary activity and muscle mass, potentially contributing to regulating weight gain. Practical applications:: Lack of physical activity is a global public health problem, which induces obesity and its associated pathologies. Approximately, 3.2 million deaths per year are attributable to lack of physical activity. CLA has previously been reported to increase voluntary and endurance activities in mice. However, the exact mode of action is not completely understood. Thus, the purpose of the study was to shed light on positive effects of CLA on physical activity through modulation of molecular targets in skeletal muscle of Nhlh2 knockout mice, which are an adult-onset inactivity induced obesity model. The current results suggest that CLA acts as a potential exercise-mimetic, resulting in increased voluntary activity and muscle mass, potentially contributing to regulating weight gain.
    Full-text · Article · Dec 2015 · European Journal of Lipid Science and Technology
    • "Up-regulation of uncoupling protein (UCP)-2 in several tissues accounts for the positive effects [11] [12] [13] [14]. The adverse effects of CLA supplementation include liver enlargement [15] [16] [17] and reduction of insulin sensitivity [18] [19] [20]. The Food and Drug Administration has approved the CLA addition to certain foods ( "
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    ABSTRACT: Clinical conditions associated with obesity can be improved by daily intake of conjugated linoleic acid (CLA) or extra virgin olive oil (EVOO). Here we investigated whether dietary supplementation with CLA and EVOO, either alone or in combination, changes body metabolism associated with mitochondrial energetics. Male C57Bl/6 mice were divided into one of four groups: CLA (1:1 cis-9, trans-11:trans-10, cis-12; 18:2 isomers), EVOO, CLA plus EVOO or control (linoleic acid). Each mouse received 3 g/kg body weight of the stated oil by gavage on alternating days for 60 days. Dietary supplementation with CLA, alone or in combination with EVOO: (a) reduced the white adipose tissue gain; (b) increased body VO2 consumption, VCO2 production and energy expenditure; (c) elevated uncoupling protein (UCP)-2 expression and UCP activity in isolated liver mitochondria. This organelle, when energized with NAD+-linked substrates, produced high amounts of H2O2 without inducing oxidative damage. Dietary supplementation with EVOO alone did not change any metabolic parameter, but supplementation with CLA itself promoted insulin resistance and elevated weight, lipid content and acetyl-CoA carboxylase-1 expression in liver. Interestingly, the in vivo antioxidant therapy with N-acetylcysteine abolished the CLA-induced rise of body metabolism and liver UCP expression and activity, while the in vitro antioxidant treatment with catalase mitigated the CLA-dependent UCP-2 expression in hepatocytes; these findings suggest the participation of an oxidative-dependent pathway. Therefore, this study clarifies the mechanisms by which CLA induces liver UCP expression and activity, and demonstrates for the first time the beneficial effects of combined CLA and EVOO supplementation.
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    • "In contrast to the chain structure of the linoleic acid, in CLA the double bonds are separated by only one single bond and occur most frequently at carbons 9 and 11 as well as 10 and 12 forming c9t11 and t10c12-CLA isomers [7]. Studies have shown that CLA isomers actively inhibit carcinogenesis [8] and prevent atherosclerosis [9], diabetes [10] [11] [12], obesity [13] [14], and osteoporosis [15] [16] [17]. Recently, it has been shown that CLA can prevent NAFLD induced by a high-fat diet [18] and influence endothelium-mediated vascular homeostasis, by reducing the release of proinflammatory mediators, such as prostaglandin E 2 and the vasoconstrictive agent thromboxane A 2 , within vascular endothelial cells [19] [20]. "
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    ABSTRACT: This study assessed the effects of individual conjugated linoleic acid isomers, c9t11-CLA and t10c12-CLA, on nonalcoholic fatty liver disease (NAFLD) and systemic endothelial dysfunction in rats fed for four weeks with control or high-fructose diet. The high-fructose diet hampered body weight gain (without influencing food intake), increased liver weight and glycogen storage in hepatocytes, upregulated expression of fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD-1), and increased saturated fatty acid (SFA) content in the liver. Both CLA isomers prevented excessive accumulation of glycogen in the liver. Specifically, t10c12-CLA decreased concentration of serum triacylglycerols and LDL + VLDL cholesterol, increased HDL cholesterol, and affected liver lipid content and fatty acid composition by downregulation of liver SCD-1 and FAS expression. In turn, the c9t11-CLA decreased LDL+VLDL cholesterol in the control group and downregulated liver expression of FAS without significant effects on liver weight, lipid content, and fatty acid composition. In summary, feeding rats with a high-fructose diet resulted in increased liver glycogen storage, indicating the induction of gluconeogenesis despite simultaneous upregulation of genes involved in de novo lipogenesis. Although both CLA isomers (c9t11 and t10c12) display hepatoprotective activity, the hypolipemic action of the t10c12-CLA isomer proved to be more pronounced than that of c9t11-CLA.
    Full-text · Article · Jun 2015
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