Abstract 688: Trans-10, Cis-12 Conjugated Linoleic Acid Induces a Lipodystrophic Phenotype and Browning of White Adipose Tissue in a Mouse Model of the Metabolic Syndrome
Trans-10, cis-12 conjugated linoleic acid (10,12 CLA) is a naturally occurring dietary trans fatty acid reported to promote weight loss by unknown mechanisms. 10,12 CLA is associated with reduced adiposity, while simultaneously promoting inflammation, insulin resistance, and dyslipidemia. Commercially available CLA supplements containing 10,12 CLA are used to facilitate weight loss, so opposing effects on body weight and inflammation could put consumers at risk for adverse health effects. We therefore examined how 10,12 CLA reduces adiposity in an obese mouse model of the metabolic syndrome. Ldlr-/- mice consuming a high fat high sucrose diet with added cholesterol (HFHSC) supplemented with 1% 10,12 CLA are resistant to weight gain, have reduced body fat, and express genes associated with fatty acid oxidation in adipose tissue. They exhibit substantial fat loss from subcutaneous but not visceral adipose depots, in stark contrast to weight matched calorically restricted mice that maintain subcutaneous fat. Further, mice consuming 10,12 CLA do not show the expected improvements in glucose metabolism or plasma lipids despite carrying significantly less fat, consistent with what is seen with lipodystrophy. Additionally, subcutaneous and brown adipose tissue contain more macrophages in 10,12 CLA-supplemented mice than in control mice, suggestive of a pro-inflammatory state. Mice supplemented with 10,12 CLA also show signs of white adipose tissue “browning” with better maintenance of core body temperature upon cold exposure, both of which were absent in the weight matched control group. In summary, 10,12 CLA induces a lipodystrophic phenotype in obese mice with fat loss specifically from subcutaneous depots, resulting in negligible improvements in glucose tolerance, plasma lipids, and adipose tissue inflammation compared to weight matched controls. Despite substandard improvements in metabolic health and the lipodystrophic phenotype seen with 10,12 CLA, the notion that such a readily available compound could increase browning of white adipose tissue has therapeutic potential, and future studies could provide insight into mechanisms by which this browning potential could be harnessed while minimizing the detrimental effects of 10,12 CLA.
Author Disclosures: L.J. den Hartigh: None. S. Wang: None. L. Goodspeed: None. A. Chait: None.
- © 2015 by American Heart Association, Inc.