title: New Insights into the High-Density Lipoprotein Dilemma.
abstract: Although high-density lipoprotein-cholesterol (HDL-C) concentration is a negative risk factor for atherosclerotic cardiovascular disease (CVD), efforts to reduce CVD risk by raising HDL-C have not been uniformly successful. Many studies have shown that alcohol consumption, that increases plasma HDL-C concentration, reduces CVD incidence. However, recent genetic studies in large populations have not only removed HDL-C from the causal link between plasma HDL-C concentration and reduced CVD risk, but also suggest that the association is weak. We propose here that the cardioprotective effects of alcohol are mediated by the interaction of its terminal metabolite, acetate, with the adipocyte free fatty acid receptor 2 (FFAR2), which elicits a profound antilipolytic effect that may increase insulin sensitivity without necessarily raising plasma HDL-C concentration.
authors.affiliation: Weill-Cornell Medicine, 6670 Bertner Avenue, Houston, TX 77030, USA. Electronic address: HJPownall@houstonmethodist.org.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Pownall
authors.affiliation: Weill-Cornell Medicine, 1305 York Avenue, New York, NY, USA.
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Gotto
mesh_terms: D000085:Acetates / Q000378:metabolism; D000438:Alcohols / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism; D050171:Dyslipidemias / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: D000085:Acetates; D000438:Alcohols; D008075:Lipoproteins, HDL; D043562:Receptors, G-Protein-Coupled
keywords: FFAR2; HDL; acetate; alcohol; atherosclerosis; dyslipidemia