Hye-Lim Noh1, Haruyo Yamashita, Ira J Goldberg. 1. Division of Preventive Medicine and Nutrition, Columbia University College of Physicians & Surgeons, 630 West 168th Street, New York, NY 10032, USA.
Abstract
INTRODUCTION: Most circulating fatty acids are contained in lipoprotein triglycerides. For the heart to acquire these lipids, they must be broken down into free fatty acids via the enzyme lipoprotein lipase (LpL). Although it has long been known that hearts primarily use esterified fatty acids as fuel, different sources of fatty acids were thought to be interchangeable. MATERIALS AND METHODS: By creating mice with neonatal and acute LpL deletion we showed that lipoprotein-derived fatty acids could not be replaced by albumin-associated free fatty acids. Loss of cardiac LpL forces the heart to increase its uptake of glucose, reduce fatty acid oxidation, and eventually leads to cardiac dysfunction. In contrast, cardiomyocyte specific overexpression of an anchored form of LpL leads to excess lipid uptake, induction of fatty acid oxidation genes, and dilated cardiomyopathy. CONCLUSION: Increasing lipid secretion from the heart or redirecting lipids to adipose tissue can alleviate this lipotoxic situation.
INTRODUCTION: Most circulating fatty acids are contained in lipoprotein triglycerides. For the heart to acquire these lipids, they must be broken down into free fatty acids via the enzyme lipoprotein lipase (LpL). Although it has long been known that hearts primarily use esterified fatty acids as fuel, different sources of fatty acids were thought to be interchangeable. MATERIALS AND METHODS: By creating mice with neonatal and acute LpL deletion we showed that lipoprotein-derived fatty acids could not be replaced by albumin-associated free fatty acids. Loss of cardiac LpL forces the heart to increase its uptake of glucose, reduce fatty acid oxidation, and eventually leads to cardiac dysfunction. In contrast, cardiomyocyte specific overexpression of an anchored form of LpL leads to excess lipid uptake, induction of fatty acid oxidation genes, and dilated cardiomyopathy. CONCLUSION: Increasing lipid secretion from the heart or redirecting lipids to adipose tissue can alleviate this lipotoxic situation.
Authors: C Ren; A Baccarelli; E Wilker; H Suh; D Sparrow; P Vokonas; R Wright; J Schwartz Journal: J Epidemiol Community Health Date: 2010-01 Impact factor: 3.710