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      Emerging Roles of Lipophagy in Health and Disease

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          Abstract

          The term lipophagy is used to describe the autophagic degradation of lipid droplets, the main lipid storage organelles of eukaryotic cells. Ever since its discovery in 2009, lipophagy has emerged as a significant component of lipid metabolism with important implications for organismal health. This review aims to provide a brief summary of our current knowledge on the mechanisms that are responsible for regulating lipophagy and the impact the process has under physiological and pathological conditions.

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          Most cited references 76

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          The role of Atg proteins in autophagosome formation.

          Macroautophagy is mediated by a unique organelle, the autophagosome, which encloses a portion of cytoplasm for delivery to the lysosome. Autophagosome formation is dynamically regulated by starvation and other stresses and involves complicated membrane reorganization. Since the discovery of yeast Atg-related proteins, autophagosome formation has been dissected at the molecular level. In this review we describe the molecular mechanism of autophagosome formation with particular focus on the function of Atg proteins and the long-standing discussion regarding the origin of the autophagosome membrane.
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            Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease

            Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem of unknown etiology that varies in prevalence among ethnic groups. To identify genetic variants contributing to differences in hepatic fat content, we performed a genome-wide association scan of nonsynonymous sequence variations (n=9,229) in a multiethnic population. An allele in PNPLA3 (rs738409; I148M) was strongly associated with increased hepatic fat levels (P=5.9×10−10) and with hepatic inflammation (P=3.7×10−4). The allele was most common in Hispanics, the group most susceptible to NAFLD; hepatic fat content was > 2-fold higher in PNPLA3-148M homozygotes than in noncarriers. Resequencing revealed another allele associated with lower hepatic fat content in African-Americans, the group at lowest risk of NAFLD. Thus, variation in PNPLA3 contributes to ethnic and inter-individual differences in hepatic fat content and susceptibility to NAFLD.
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              Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase.

              Mobilization of fatty acids from triglyceride stores in adipose tissue requires lipolytic enzymes. Dysfunctional lipolysis affects energy homeostasis and may contribute to the pathogenesis of obesity and insulin resistance. Until now, hormone-sensitive lipase (HSL) was the only enzyme known to hydrolyze triglycerides in mammalian adipose tissue. Here, we report that a second enzyme, adipose triglyceride lipase (ATGL), catalyzes the initial step in triglyceride hydrolysis. It is interesting that ATGL contains a "patatin domain" common to plant acyl-hydrolases. ATGL is highly expressed in adipose tissue of mice and humans. It exhibits high substrate specificity for triacylglycerol and is associated with lipid droplets. Inhibition of ATGL markedly decreases total adipose acyl-hydrolase activity. Thus, ATGL and HSL coordinately catabolize stored triglycerides in adipose tissue of mammals.
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                Author and article information

                Contributors
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                10 September 2019
                2019
                : 7
                Affiliations
                [1] 1Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology – Hellas , Heraklion, Greece
                [2] 2Department of Basic Sciences, Medical School, University of Crete , Heraklion, Greece
                [3] 3Department of Chemistry, University of Crete , Heraklion, Greece
                Author notes

                Edited by: Tassula Proikas-Cezanne, University of Tübingen, Germany

                Reviewed by: George Simos, University of Thessaly, Greece; Xinjian Liu, Sun Yat-sen University, China

                *Correspondence: Nektarios Tavernarakis, tavernarakis@ 123456imbb.forth.gr

                These authors have contributed equally to this work

                This article was submitted to Cell Death and Survival, a section of the journal Frontiers in Cell and Developmental Biology

                Article
                10.3389/fcell.2019.00185
                6746960
                d2159fc4-d047-4307-9343-9b61d7090c92
                Copyright © 2019 Kounakis, Chaniotakis, Markaki and Tavernarakis.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 95, Pages: 8, Words: 0
                Categories
                Cell and Developmental Biology
                Review

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