Conjugated linoleic acid reduces adiposity and increases markers of browning and inflammation in white adipose tissue of mice

Kristina Martinez,Lin Xi,Robin Hopkins,J Mark Brown,Michael Mcintosh,Tanya Reid,Chia-Chi Chuang,Wan Shen,Lindsay Hixson,Joseph Starnes

doi:10.1194/jlr.m030924

Abstract

The objective of this study was to examine the mechanism by which conjugated linoleic acid (CLA) reduces body fat. Young male mice were fed three combinations of fatty acids at three doses (0.06%, 0.2%, and 0.6%, w/w) incorporated into AIN76 diets for 7 weeks. The types of fatty acids were linoleic acid (control), an equal mixture of trans-10, cis-12 (10,12) CLA plus linoleic acid, and an equal isomer mixture of 10,12 plus cis-9, trans-11 (9,11) CLA. Mice receiving the 0.2% and 0.6% dose of 10,12 CLA plus linoleic acid or the CLA isomer mixture had decreased white adipose tissue (WAT) and brown adipose tissue (BAT) mass and increased incorporation of CLA isomers in epididymal WAT and liver. Notably, in mice receiving 0.2% of both CLA treatments, the mRNA levels of genes associated with browning, including uncoupling protein 1 (UCP1), UCP1 protein levels, and cytochrome c oxidase activity, were increased in epididymal WAT. CLA-induced browning in WAT was accompanied by increases in mRNA levels of markers of inflammation. Muscle cytochrome c oxidase activity and BAT UCP1 protein levels were not affected by CLA treatment. These data suggest a linkage between decreased adiposity, browning in WAT, and low-grade inflammation due to consumption of 10,12 CLA.

Highlights

The objective of this study was to examine the mechanism by which conjugated linoleic acid (CLA) reduces body fat
We demonstrated that an intermediate dose of 10,12 CLA (i.e., 0.1% 10,12 CLA plus 0.1% linoleic acid) or the CLA isomer mixture (i.e., 0.1% 10,12 CLA plus 0.1% 9,11 CLA) i) incorporated into white adipose tissue (WAT) and liver, ii) decreased total WAT depot weight, iii) increased the mRNA levels of markers of browning, browning activators, and low-grade inflammation, and iv) increased the protein levels of uncoupling protein 1 (UCP1), carnitine palmitoyltransferase (CPT)-1b, and COX-2 and the activity of cytochrome c oxidase in epididymal (EPI) WAT without decreasing food intake or causing steatosis or insulin resistance
GPR40 [35, 36] and GPR120 [30, 37] are activated by long-chain FFA, and their activation is associated with increased intracellular calcium levels and extracellular signal-related kinase (ERK) activation, similar to what we have shown in human adipocytes treated with 10,12 CLA [38]

Summary

Introduction

The objective of this study was to examine the mechanism by which conjugated linoleic acid (CLA) reduces body fat. It has been reported that only the 10,12 CLA isomer reduces adiposity or delipidates adipocytes; at relatively high doses it causes adverse side effects in Abbreviations: AUC, area under the curve; BAT, brown adipose tissue; BMR, basal metabolic rate; 9,11 CLA, cis-9, trans-11 conjugated linoleic acid; 10,12 CLA, trans-10, cis-12 conjugated linoleic acid; Cidea, cell death-induced DNA fragmentation factor-a-like effector A; Cox8b, cytochrome c oxidase subunit VIII b; COX-2, cyclooxygenase-2; CPT, carnitine palmitoyltransferase; Elovl, elongation of very long chain fatty acids 3 protein; EPI, epididymal; ER, endoplasmic reticulum; ERK, extracellular signal-regulated kinase; FABP, fatty acid binding protein; GPCR, G protein-coupled receptor; GPR, G protein receptor; GTT, glucose tolerance test; ING, inguinal; IL, interleukin; MAPK, mitogenactivated protein kinase; MCP, monocyte chemoattractant protein; MEK, MAPK kinase; Mrc, mannose receptor c; NF-␬B, nuclear factor kappa B; PPAR, peroxisome proliferator activated receptor; PG, prostaglandin; RET, retroperitoneal; TBP, TATA-binding protein; TG, triglyceride; TMEM 26, transmembrane protein 26; TNF␣, tumor necrosis factor ␣; UCP, uncoupling protein; WAT, white adipose tissue

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