Anti-obesity mechanisms of conjugated linoleic acid (CLA): role of inflammatory signaling and browning in white adipose tissue

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Wan Shen (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Michael McIntosh

Abstract: Overweight and obesity are the most widespread nutritional diseases in the U.S., which greatly increase chronic disease risks and mortality. Therefore, it is urgent to develop a relatively efficacious and safe strategy for the weight management. Consumption of conjugated linoleic acid (CLA) supplements or one of its isomers, trans-10, cis-12 (10,12) CLA, has consistently demonstrated reductions in body weight or body fat in human and animal studies. Our lab has demonstrated that 10,12 CLA triggered calcium release from endoplasmic reticulum in human primary adipocytes, which activated downstream inflammatory signaling, resulting in impaired uptake of glucose and fatty acid, and delipidation. However, the upstream signals responsible for these actions are unknown. Therefore, my Aim 1 investigated the upstream mechanism by which 10,12 CLA increases intracellular calcium and inflammatory signaling in human primary adipocytes. The results indicated that phospholipase C plays an important role in 10,12 CLA-mediated activation of intracellular calcium accumulation, inflammatory signaling, delipidation, and insulin resistance in human primary adipocytes. It has been demonstrated that 10,12 CLA increased mRNA levels and protein levels of cyclooxygenase-2 (COX-2) and pro-inflammatory prostaglandins, which have been linked to increased energy expenditure associated with white adipose tissue (WAT) browning and uncoupling of ATP synthesis. It also has been shown that relatively high doses of 10,12 CLA lead to more significant reductions in body fat, but cause a greater level of inflammation, insulin resistance, and steatosis in animals. Therefore, Aims 2 and Aim 3 determined the extent to which a relative low dose of 10,12 CLA or a CLA isomer mixture increases markers of browning in mice and its dependence in inflammatory signaling. In Aim 2, a low threshold dose of 10,12 CLA was found that prevented body fat accumulation with minimum metabolic side-effects in non-obese mice. It was also found that 10,12 CLA-induced browning in WAT was accompanied by increases in mRNA levels of COX-2 and other markers of inflammation. In Aim 3, a relatively low dose of 10,12 CLA reduced body fat and increased browning of WAT in overweight mice, which were independent of inflammatory signaling. Collectively, these findings provide critical insights for the development of reliable dietary strategies for people who take CLA as method to lose weight. However, we still do not know (i) if 10,12 CLA supplementation would effectively reduce body fat in overweight mice when they are continuously fed an American-type, high-fat diet; (ii) potential risks of impaired regulation of body temperature, inflammation, and steatosis due to 10,12 CLA consumption in high fat-fed mice; and (iii) potential mechanisms by which 10,12 CLA reduces body fat in high fat-fed mice.

Additional Information

Publication
Dissertation
Language: English
Date: 2015
Keywords
Browning, Conjugated linoleic acid, Dietary supplement, Inflammation, Weight loss
Subjects
Linoleic acid $x Physiological effect
Obesity
Weight loss

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