Low level of trans-10, cis-12 conjugated linoleic acid decreases adiposity and increases browning independent of inflammatory signaling in overweight Sv129 mice

Abstract

The objective of this study was to determine the extent to which a low level of trans-10, cis-12 (10,12) conjugated linoleic acid (CLA) decreases adiposity and increases browning in overweight mice, its dependence on inflammatory signaling, and potential synergistic effects of daily exercise. Young, Sv129 male mice were fed a high fat diet for 5 wk to make them fat and glucose intolerant, and then switch them to a low fat diet with or without 0.1% 10,12 CLA, sodium salicylate, or exercise for another 7 wk. 10,12 CLA decreased white adipose tissue (WAT) and brown adipose tissue mass, and increased the mRNA and protein levels, and activities of enzymes associated with thermogenesis or fatty acid oxidation in WAT. Mice fed 10,12 CLA had lower body temperatures compared to controls during cold exposure, which coincided with decreased adiposity. Although sodium salicylate decreased 10,12 CLA-mediated increases in markers of inflammation in WAT, it did not affect other outcomes. Exercise had no further effect on the outcomes measured. Collectively, these data indicate that 10,12 CLA-mediated reduction of adiposity is independent of inflammatory signaling, and possibly due to up-regulation of fatty acid oxidation and heat production in order to regulate body temperature. Although this low level of 10,12 CLA reduced adiposity in overweight mice, hepatomegaly and inflammation are major health concerns.

Metabolically distinct weight loss by 10,12 CLA and caloric restriction highlight the importance of subcutaneous white adipose tissue for glucose homeostasis in mice

“…Our studies confirm and extend previous reports that 10,12 CLA is associated with browning of WAT [ 11 , 62 ]. Moreover, 10,12 CLA failed to activate BAT (assessed by Ucp1 mRNA and protein levels), also consistent with previous findings [ 62 ].…”

“…Previous evidence suggests that weight loss induced by 10,12 CLA in mice [ 11 ] and humans [ 12 ] is accompanied by increased adipose tissue fatty acid oxidation (FAO), a lipid catabolic pathway uncommonly used by adipocytes. In striking contrast to the lipogenic effects of other fatty acids such as palmitate and 9,11 CLA, we and others have shown that cultured adipocytes treated with 10,12 CLA display a pro-inflammatory phenotype with increased mitochondrial respiration and FAO [ 13 , 14 ].…”

Alpha-Linolenic Acid-Enriched Butter Promotes Fatty Acid Remodeling and Thermogenic Activation in the Brown Adipose Tissue

“…In addition, there is growing evidence showing that conjugated linoleic acid (CLA), either trans-10 or cis-12 isomer alone, or the mixture with cis-9 and trans-11 isomer, increases the thermogenic activity in the adipose tissue [35][36][37]. The thermogenic action of CLA is most evident in the WAT with a minor impact on the BAT [37]. It is quite distinctive from the thermogenic activity exerted by ALA enrichment in this work, since n3Bu supplementation promotes thermogenesis in the BAT, while causes a minimal impact on the WAT.…”

Small molecules for fat combustion: targeting obesity

“…CLA led to reduction in percentage of body fat, and increased UCP1 level and fatty acid oxidation 117. , 118. 12,13-Dihydroxy-9 Z -octadecenoic acid (12,13-diHOME), a lipid to stimulate BAT activity, is negatively correlated with body-mass index.…”