10,12 Conjugated Linoleic Acid-Driven Weight Loss Is Protective against Atherosclerosis in Mice and Is Associated with Alternative Macrophage Enrichment in Perivascular Adipose Tissue
Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington Medicine Diabetes Institute, University of Washington, Box 358062, 750 Republican Street, Seattle, WA 98109, USA
Department of Medicine, Cardiology, University of Washington, Box 356422, 1959 Pacific Ave NE, Seattle, WA 98195, USA
Author to whom correspondence should be addressed.
Nutrients 2018, 10(10), 1416; https://doi.org/10.3390/nu10101416
Received: 4 September 2018 / Revised: 26 September 2018 / Accepted: 27 September 2018 / Published: 3 October 2018
(This article belongs to the Special Issue Fatty Acids and Cardiometabolic Health)
The dietary fatty acid 10,12 conjugated linoleic acid (10,12 CLA) promotes weight loss by increasing fat oxidation, but its effects on atherosclerosis are less clear. We recently showed that weight loss induced by 10,12 CLA in an atherosclerosis-susceptible mouse model with characteristics similar to human metabolic syndrome is accompanied by accumulation of alternatively activated macrophages within subcutaneous adipose tissue. The objective of this study was to evaluate whether 10,12 CLA-mediated weight loss was associated with an atheroprotective phenotype. Male low-density lipoprotein receptor deficient (Ldlr−/−) mice were made obese with 12 weeks of a high-fat, high-sucrose diet feeding (HFHS: 36% fat, 36% sucrose, 0.15% added cholesterol), then either continued on the HFHS diet with or without caloric restriction (CR), or switched to a diet with 1% of the lard replaced by either 9,11 CLA or 10,12 CLA for 8 weeks. Atherosclerosis and lipid levels were quantified at sacrifice. Weight loss in mice following 10,12 CLA supplementation or CR as a weight-matched control group had improved cholesterol and triglyceride levels, yet only the 10,12 CLA-treated mice had improved en face and aortic sinus atherosclerosis. 10,12 CLA-supplemented mice had increased lesion macrophage content, with enrichment of surrounding perivascular adipose tissue (PVAT) alternative macrophages, which may contribute to the anti-atherosclerotic effect of 10,12 CLA.