PMID- 32698101 OWN - NLM STAT- MEDLINE DCOM- 20211012 LR - 20211012 IS - 1532-2238 (Electronic) IS - 1096-6374 (Linking) VI - 53-54 DP - 2020 Aug-Oct TI - Growth hormone ameliorates high glucose-induced steatosis on in vitro cultured human HepG2 hepatocytes by inhibiting de novo lipogenesis via ChREBP and FAS suppression. PG - 101332 LID - S1096-6374(20)30041-1 [pii] LID - 10.1016/j.ghir.2020.101332 [doi] AB - OBJECTIVE: Growth hormone (GH) deficiency has been associated with increased steatosis but the molecular mechanism has not been fully elucidated. We investigated the effect of GH on lipid accumulation of HepG2 cells cultured on an in vitro steatosis model and examined the potential involvement of insulin-like growth factor 1 (IGF-1) as well as lipogenic and lipolytic molecules. METHODS: Control and steatosis conditions were induced by culturing HepG2 cells with 5.5 or 25 mmol/l glucose for 24 h, respectively. Afterward, cells were exposed to 0, 5, 10 or 20 ng/ml GH for another 24 h. Lipid content was quantified as well as mRNA and protein levels of IGF-1, carbohydrate responsive element-binding protein (ChREBP), sterol regulatory element-binding protein 1c (SREBP1c), fatty acid synthase (FAS), carnitine palmitoyltransferase 1A (CPT1A), and peroxisome proliferator-activated receptor alpha (PPAR-alpha) by qPCR and western blot, respectively. Data were analyzed by one-way ANOVA and the Games-Howell post-hoc test. RESULTS: In the steatosis model, HepG2 hepatocytes showed a significant 2-fold increase in lipid amount as compared to control cells. IGF-1 mRNA and protein levels were significantly increased in control cells exposed to 10 ng/ml GH, whereas high glucose abolished this effect. High glucose also significantly increased both mRNA and protein of ChREBP and FAS without having effect on SREBP1c, CPT1A and PPAR-alpha. However, GH inhibited ChREBP and FAS production, even in HepG2 hepatocytes cultured under steatosis conditions. CONCLUSIONS: Growth hormone ameliorates high glucose-induced steatosis in HepG2 cells by suppressing de novo lipogenesis via ChREBP and FAS down-regulation. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Villanueva-Ortega, Erendira AU - Villanueva-Ortega E AD - Laboratory for Proteomics and Metabolomics, Research Division, General Hospital of Mexico "Dr. Eduardo Liceaga", 06720, Mexico City, Mexico.; Department of Genetics, General Hospital of Mexico "Dr. Eduardo Liceaga", 06720, Mexico City, Mexico. FAU - Mendez-Garcia, Lucia A AU - Mendez-Garcia LA AD - Laboratory for Proteomics and Metabolomics, Research Division, General Hospital of Mexico "Dr. Eduardo Liceaga", 06720, Mexico City, Mexico. FAU - Garibay-Nieto, Guadalupe N AU - Garibay-Nieto GN AD - Department of Genetics, General Hospital of Mexico "Dr. Eduardo Liceaga", 06720, Mexico City, Mexico. FAU - Laresgoiti-Servitje, Estibalitz AU - Laresgoiti-Servitje E AD - Clinical Medical Sciences, School of Medicine, Tecnologico de Monterrey, Campus Ciudad de Mexico, 14380, Mexico City, Mexico. FAU - Medina-Bravo, Patricia AU - Medina-Bravo P AD - Endocrinology Department, Hospital Infantil de Mexico Federico Gomez, 06720, Mexico City, Mexico. FAU - Olivos-Garcia, Alfonso AU - Olivos-Garcia A AD - Experimental Research Unit, School of Medicine, Universidad Nacional Autonoma de Mexico, General Hospital of Mexico "Dr. Eduardo Liceaga", 06720, Mexico City, Mexico. FAU - Munoz-Ortega, Martin H AU - Munoz-Ortega MH AD - Universidad Autonoma de Aguascalientes, Departamento de Morfologia, Centro de Ciencias Basicas, Edificio 202, Av. Universidad 940 Ciudad Universitaria C.P. 20130, Aguascalientes, Ags., Mexico. FAU - Ventura-Juarez, Javier AU - Ventura-Juarez J AD - Universidad Autonoma de Aguascalientes, Departamento de Morfologia, Centro de Ciencias Basicas, Edificio 202, Av. Universidad 940 Ciudad Universitaria C.P. 20130, Aguascalientes, Ags., Mexico. FAU - Escobedo, Galileo AU - Escobedo G AD - Laboratory for Proteomics and Metabolomics, Research Division, General Hospital of Mexico "Dr. Eduardo Liceaga", 06720, Mexico City, Mexico.. Electronic address: gescobedo@unam.mx. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200715 PL - Scotland TA - Growth Horm IGF Res JT - Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society JID - 9814320 RN - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors) RN - 0 (MLXIPL protein, human) RN - 0 (Sweetening Agents) RN - 12629-01-5 (Human Growth Hormone) RN - EC 2.3.1.85 (Fatty Acid Synthases) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*antagonists & inhibitors MH - Fatty Acid Synthases/*antagonists & inhibitors MH - Glucose/*adverse effects MH - Hep G2 Cells MH - Hepatocytes/*drug effects/metabolism/pathology MH - Human Growth Hormone/*pharmacology MH - Humans MH - *Lipogenesis MH - Non-alcoholic Fatty Liver Disease/chemically induced/metabolism/pathology/*prevention & control MH - Sweetening Agents/adverse effects OTO - NOTNLM OT - ChREBP OT - FAS OT - Growth hormone OT - HepG2 cells OT - IGF-1 OT - Steatosis COIS- Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this manuscript. Declaration of interests The authors Erendira Villanueva-Ortega, Lucia A. Mendez-Garcia, Guadalupe N. Garibay-Nieto, Estibalitz Laresgoiti-Servitje, Patricia Medina-Bravo, Alfonso Olivos-Garcia, Martin H. Munoz-Ortega, Javier Ventura-Juarez, and Galileo Escobedo, of the manuscript entitled "Growth hormone ameliorates steatosis by inhibiting ChREBP and FAS expression on in vitro cultured human HepG2 hepatocytes" declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/07/23 06:00 MHDA- 2021/10/13 06:00 CRDT- 2020/07/23 06:00 PHST- 2019/10/17 00:00 [received] PHST- 2020/05/13 00:00 [revised] PHST- 2020/06/01 00:00 [accepted] PHST- 2020/07/23 06:00 [pubmed] PHST- 2021/10/13 06:00 [medline] PHST- 2020/07/23 06:00 [entrez] AID - S1096-6374(20)30041-1 [pii] AID - 10.1016/j.ghir.2020.101332 [doi] PST - ppublish SO - Growth Horm IGF Res. 2020 Aug-Oct;53-54:101332. doi: 10.1016/j.ghir.2020.101332. Epub 2020 Jul 15.