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

Abstract

mixtures of cis -9, trans -11 (9,11) conjugated linoleic acid (CLA) and trans -10, cis -12 (10,12) CLA. Indeed, consuming a mixture of these CLA isomers, or 10,12 CLA alone, reduced body fat in many animal (reviewed in Ref. 3 ) and human studies ( 4 ). Rodents that consumed higher amounts of the CLA than humans (e.g., 0.5-1.5% CLA in the diet or 600-1,800 mg/kg body weight) lost body fat more rapidly but concurrently developed side effects, including chronic infl ammation, insulin resistance, and lipoatrophy ( 5 ). Notably, intermediate levels of mixed CLA isomers (i.e., 0.1-0.3%, w/w) reduced adiposity in mice without adversely affecting liver weight or lipid content ( 6 ). However, individual isomers were not fed, the level of reduction in adiposity in the 0.1% group was marginal, and anti-obesity mechanisms were not identifi ed ( 6 ). In contrast, clinical trials routinely use lower doses of CLA (e.g., 3-6 g/day or 35-70 mg/kg body weight), although the relative decrease in adiposity is not as rapid or great as in the higher doses used in rodent studies.It has been reported that only the 10,12 CLA isomer reduces adiposity or delipidates adipocytes; however, at relatively high doses it also causes adverse side effects in 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 infl ammation. 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 infl ammation due to consumption of 10,12 CLA.

c9,t11-Conjugated linoleic acid ameliorates steatosis by modulating mitochondrial uncoupling and Nrf2 pathway

“…In this experimental condition, the pathological signs were improved by both individual CLA isomer supplements; however, 9,11-CLA administration more effectively downregulates pathological changes in the liver (macro-and microvesicular hepatic steatosis and oxidative stress) and in the serum (ALT, GGT, proinfl ammatory cytokines, and chemokines) compared with 10,12-CLA treatment. These results are consistent with the reported different health benefi ts elicited by individual CLA isomers ( 14 ), but the favorable effects exhibited by 10,12-CLA are not in complete agreement with a recent review showing its steatogenic activity ( 33,38 ). The explanation for this discrepancy can be attributed to dosage as well as the different treatments or animal models used.…”

Adipose tissue adaptive response totrans‐10,cis‐12‐conjugated linoleic acid engages alternatively activated M2 macrophages

“…A notable exception is arginase 1 gene expression, which is not significantly affected. We can speculate that the lower degree of stimulation of M2 markers in Shen's study (28), compared with our current data, relies on the distinct sensitivity between male and female mice and between different mouse strains. The mode of t10,c12-CLA administration could also be a factor.…”

“…In a recent study (28), 129Sv male mice were provided with semipurified diets enriched with increasing amounts of t10,c12-CLA (0.03, 0.1, and 0.3% w/w) for 7 wk. Mice receiving the highest dose of the compound displayed increased MCP1, F4/80, TNFa, and IL-6 gene expression in WAT, in line with our current and earlier observations (18).…”

Trans-10,cis-12-conjugated linoleic acid worsens renal pathology and alters cyclooxygenase derived oxylipins in obesity-associated nephropathy

“…On the other hand, studies in humans have documented elevated levels of C-reactive protein with t10,c12 CLA and elevated isoprostanes with supplementation with either isomer [37,38]. Others have reported that t10,c12 CLA promotes adipose tissue inflammation in mouse adipose tissue, 3T3-L1 preadipocytes and primary human adipocytes [39][40][41][42]. The effect of dietary CLA isomers on the kidney within the context of the obese state remains to be determined.…”