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Grant Abstract: Cardiovascular Disease and Diabetes Program Project

Grant Number: 5P01HL092969-55S1
PI Name: Bornfeldt
Project Title: Cardiovascular Disease and Diabetes Program Project

Abstract: A major theme of the parent Program Project is to understand the role of HDL in protecting against cardiovascular disease, and how HDL can become dysfunctional. Project 3 is specifically investigating the anti-inflammatory effect of HDL on adipocytes and adipose tissue. Important findings to date show that while HDL isolated from healthy human subjects and chow-fed mice inhibits chemokine and cytokine expression stimulated by the saturated fatty acid, palmitate, HDL from mice and humans with evidence of systemic inflammation loses these anti-inflammatory properties. We now plan to investigate the role of 10, 12 CLA, a component of a dietary supplement that is widely used to facilitate weight loss, on HDL composition and function. We previously have shown that 10,12 CLA supplementation leads to weight loss in obese mice, with parallel reductions in plasma cholesterol, triglycerides, LDL and VLDL levels, although HDL-cholesterol levels remained unchanged. Although the improvements in lipids and lipoproteins were much more dramatic in a weight-matched cohort of calorically restricted mice, 10,12 CLA supplementation resulted in a greater decrease in atherosclerosis, suggesting that factors other than plasma lipoprotein levels are playing a role in reducing atherosclerosis. One possibility is that 10,12 CLA is affecting HDL function without changing HDL cholesterol content. In support of this, we have preliminary data showing that HDL from 10,12 CLA supplemented mice had stronger anti-inflammatory effects on adipocytes than control HDL, suggesting a potential added benefit from 10,12 CLA supplementation. Therefore, in this one year supplement to our Program Project we now plan to determine if 10,12 CLA leads to beneficial changes in the anti-inflammatory effects of HDL and in the HDL proteome and/or HDL particle number, and to evaluate the cholesterol efflux capacity of HDL isolated from 10,12 CLA-supplemented mice in adipocytes and macrophages. These findings should provide important information about potential translational use of this dietary supplement to affect HDL composition and function, and how it compares to weight loss due to caloric restriction.

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