Conjugated Linoleic Acid: Mechanisms of Fat Loss

Conjugated linoleic acid (CLA) is a structural isomer of linoleic acid found naturally in the milk and meat of ruminant animals, where it is synthesised via bacterial fermentation. Studies investigating the effects of CLA have shown that it is able to cause delipidation in adipocytes and this may account for some of the fat loss effects of consuming dairy products. Dietary supplements containing CLA are available and have been shown to be effective at causing fat loss. The two main isomers of CLA in the human diet are trans-10, cis-12 (18:2t10, c12) and cis-9, trans-11 (18:2c9, t11) CLA, with cis-9, trans-11 being the predominant form found in dairy products. Over 15 clinical trials and 30 animal studies have shown that consuming an equal mixture of trans-10, cis-12 and cis-9, trans-11 CLA or trans-10, cis-12 CLA alone is able to reduce body fat or increase fat free mass. Equal mixtures of cis-9, trans-11 and trans-10, cis-12 are found in most dietary supplements, but only the trans-10, cis-12 isomer causes adipocyte delipidation.

A number of studies have explored the possible mechanisms of action by which CLA might be able to cause fat loss or increases in lean mass. Amongst the mechanisms suggested include stimulation of lipolysis, inhibition of adipogenesis, increases in energy expenditure and the promotion of adipocyte apoptosis. The ability of trans-10, cis-12 CLA to cause adipocyte delipidation may be dependent on intracellular inflammatory signalling and the release of intracellular calcium from the endoplasmic reticulum. The upregulation of inflammatory pathways by trans-10, cis-12 CLA may cause the increase release of inflammatory markers such as nuclear factor kappa B (NFκB), activator protein-1 and mitogen-activated protein kinase (MAPK), which then cause inhibition of peroxisome proliferator-activated receptor (PPARγ), and reductions in glucose uptake, fatty acid uptake and de novo lipogenesis. These intracellular changes might be triggered by the upstream activation of the phospholipase C (PLC) membrane bound receptor.

In a recent study published in the Journal of Nutrition1, researchers tested the hypothesis that the cellular changes induced by trans-10, cis-12 CLA were caused by activation of the PLC and the diacylglycerol (DAG) and inositol phosphate (IP3) pathway. Researchers pretreated primary culture adipocytes with the PLC inhibitor U73122 and then exposed the cells to trans-10, cis-12 CLA. The treated cells showed attenuation of insulin resistance within 48 hours of treatment and reductions in mRNA levels of PPARγ, insulin stimulated glucose transporter-4, acetyl CoA carboxylase-1 and stearoyl-CoA desaturase-1, as well as decreased protein levels of PPARγ, within 24 hours. Treatment with U73122 also decreased the inflammatory related calcium/calmodulin-dependent protein kinase-β, cyclooxygenase-2, monocyte chemoattractant protein-1, interleukin-6 and interleukin-8, as well as the activation of extracellular signal-related kinase, c-Jun N-terminal kinase and c-Jun within 24 hours.

These results support the current hypothesis and suggests that trans-10, cis-12 CLA activates the membrane bound PLC, and this in turn activates the DAG and IP3 second messengers that increase cellular inflammatory signalling. In fact the presence of trans-10, cis-12 CLA increased PLC within the membrane of the cultured cells within 3 minutes. Interestingly, the results of this study also showed that the trans-10, cis-12 isomer of CLA was able to increase intracellular calcium concentrations within 3 minutes and increase mRNA levels of heat shock proteins within 6 to 24 hours, both of which were inhibited by the presence of U73122. Heat shock proteins are linked to the cellular accumulation of calcium and inflammatory signal pathways. Taken as a whole this study suggest that trans-10, cis-12 CLA causes intracellular calcium accumulation and inflammatory signalling. This is hypothesised in turn to results in insulin resistance in adipocytes and this decreases the uptake of glucose, fatty acids and subsequently decrease lipogenesis.

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1Shen, W., Martinez, K., Chi, C. and McIntosh, M. 2013. The phospholipase C inhibitor U73122 attenuates trans-10, cis-12 conjugated linoleic acid-mediated inflammatory signalling and insulin resistance in human adipocytes. Journal of Nutrition. 143: 584-590

About Robert Barrington

Robert Barrington is a writer, nutritionist, lecturer and philosopher.
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