title: Lecithin cholesterol acyltransferase deficiency protects from diet-induced insulin resistance and obesity--novel insights from mouse models.
abstract: Reduced plasma level of high-density lipoprotein cholesterol is an independent risk factor for atherosclerotic heart disease and is also a major diagnostic feature for the metabolic syndrome. Lecithin cholesterol acyltransferase (LCAT), an enzyme mediating the esterification of cholesterol in circulating lipoproteins, is one of the major modulators of high-density lipoprotein levels and composition. Loss-of-function mutations of LCAT invariably results in profound HDL deficiency and also modest hypertriglyceridemia (HTG). While intense effort has been devoted to investigate the role of LCAT in atherogenesis, which remains controversial, much less is known about whether LCAT also modulates glucose and energy homeostasis. In recent years, findings from studying the LCAT knockout mice began to suggest that LCAT deficiency, in spite of its unfavorable high triglyceride/low HDL lipid phenotypes, may confer protection from the development of insulin resistance and obesity. To date, alterations in specific metabolic pathways in liver, white adipose tissue, and skeletal muscle have been implicated. A better mechanistic understanding in the metabolic linkage between the primary biochemical action of LCAT and the downstream protective phenotypes will greatly facilitate the identification of potential novel pathways and targets in the treatment of obesity and diabetes.
authors: Keenan Research Center, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada. ngd@smh.ca
authors: Dominic S
authors: DS
authors: Ng
mesh_terms: D000818:Animals; D004032:Diet / Q000009:adverse effects*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D009765:Obesity / Q000378:metabolism*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics / Q000378:metabolism*
chemical_list: D007862:Phosphatidylcholine-Sterol O-Acyltransferase