title: Triglyceride Mobilization from Lipid Droplets Sustains the Anti-Steatotic Action of Iodothyronines in Cultured Rat Hepatocytes.
abstract: Adipose tissue, dietary lipids and de novo lipogenesis are sources of hepatic free fatty acids (FFAs) that are stored in lipid droplets (LDs) as triacylglycerols (TAGs). Destiny of TAGs stored in LDs is determined by LD proteomic equipment. When adipose triglyceride lipase (ATGL) localizes at LD surface the lipid mobilization is stimulated. In this work, an in vitro model of cultured rat hepatocytes mimicking a mild steatosis condition was used to investigate the direct lipid-lowering action of iodothyronines, by focusing, in particular, on LD-associated proteins, FFA oxidation and lipid secretion. Our results demonstrate that in "steatotic" hepatocytes iodothyronines reduced the lipid excess through the recruitment of ATGL on LD surface, and the modulation of the LD-associated proteins Rab18 and TIP47. As an effect of ATGL recruitment, iodothyronines stimulated the lipid mobilization from LDs then followed by the up-regulation of carnitine-palmitoyl-transferase (CPT1) expression and the stimulation of cytochrome-c oxidase (COX) activity that seems to indicate a stimulation of mitochondrial function. The lipid lowering action of iodothyronines did not depend on increased TAG secretion. On the basis of our data, ATGL could be indicated as an early mediator of the lipid-lowering action of iodothyronines able to channel hydrolyzed FFAs toward mitochondrial beta-oxidation rather than secretion.
authors.affiliation: Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, Università di GenovaGenova, Italia; Istituto Nazionale Biostrutture e BiosistemiRoma, Italia.
authors.forename: Elena
authors.initials: E
authors.lastname: Grasselli
authors.affiliation: Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, Università di Genova Genova, Italia.
authors.forename: Adriana
authors.initials: A
authors.lastname: Voci
authors.affiliation: Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, Università di Genova Genova, Italia.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Demori
authors.affiliation: Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, Università di Genova Genova, Italia.
authors.forename: Giulia
authors.initials: G
authors.lastname: Vecchione
authors.affiliation: Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, Università di Genova Genova, Italia.
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Compalati
authors.affiliation: Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, Università di Genova Genova, Italia.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gallo
authors.affiliation: Dipartimento di Scienze e Tecnologie, Università del Sannio Benevento, Italia.
authors.forename: Fernando
authors.initials: F
authors.lastname: Goglia
authors.affiliation: Dipartimento di Scienze Biomolecolari, Università di Urbino Urbino, Italia.
authors.forename: Rita
authors.initials: R
authors.lastname: De Matteis
authors.affiliation: Dipartimento di Scienze e Tecnologie, Università del Sannio Benevento, Italia.
authors.forename: Elena
authors.initials: E
authors.lastname: Silvestri
authors.affiliation: Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, Università di GenovaGenova, Italia; Istituto Nazionale Biostrutture e BiosistemiRoma, Italia.
authors.forename: Laura
authors.initials: L
authors.lastname: Vergani
keywords: adipose triglyceride lipase; in vitro steatosis; iodothyronines; lipid droplet; lipid lowering action; mitochondrial fatty acid oxidation; primary cultured rat hepatocytes