Lipid droplet disposal in non-alcoholic fatty liver disease after sleeve gastrectomy

G Angelini; L Castagneto Gissey; E Capristo; M Manco; AL Binkerfeld; S Bornstein; C Giordano; G Mingrone; G Casella

doi:10.1055/s-0039-1688325

Diabetologie und Stoffwechsel, Table of Contents

Diabetologie und Stoffwechsel 2019; 14(S 01): S75
DOI: 10.1055/s-0039-1688325

Poster

Insulinwirkung und Fettleber

Georg Thieme Verlag KG Stuttgart · New York

Lipid droplet disposal in non-alcoholic fatty liver disease after sleeve gastrectomy

G Angelini

¹Catholic University of Sacred Heart, Internal Medicine, Rome, Italy

,

L Castagneto Gissey

²Sapienza University of Rome, Rome, Italy, Department of Surgical Sciences, 2, Italy

,

E Capristo

³Università Cattolica del S. Cuore, Internal Medicine, Rome, Italy

,

M Manco

⁴Bambino Gesù Children's Hospital, Research Unit for Multi-factorial Diseases, Obesity and Diabetes, Rome, Italy

,

AL Binkerfeld

⁵Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Department of Medicine III, Dresden, Germany

,

S Bornstein

⁵Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Department of Medicine III, Dresden, Germany

,

C Giordano

⁶Sapienza University of Rome, Department of Radiological, Oncological and Pathological Sciences, Rome, Italy

,

G Mingrone

³Università Cattolica del S. Cuore, Internal Medicine, Rome, Italy

,

G Casella

⁶Sapienza University of Rome, Department of Radiological, Oncological and Pathological Sciences, Rome, Italy

› Author Affiliations

Abstract

Full Text

Background and aims:

Other than promoting type2-diabetes remission, bariatric-surgery (BS) reverses also the hepatic features of non-alcoholic fatty-liver disease (NAFLD). However, the mechanism of NAFLD formation and reversal is poorly understood. We aimed to study whether Plin2 protein expression is influenced by sleeve-gastrectomy (SG) through the improvement of chaperone-mediated autophagy (CMA).

Methods:

We performed sleeve-gastrectomy (SG) in rats with diet-induced obesity (DIO) and in obese NAFLD-humans. Insulin-signaling (Akt-Ser473, GSK-3α/β-Ser21/9, FOXO1a-Thr24) and chaperone-mediated autophagy (LAMP2A, Plin2) was assessed in the liver and monocytes. Liver and monocytes were stained for lipid and glycogen accumulation. Primary cultured hepatocyte and monocytes of control subjects were transfected with human-Plin2-plasmid to measured insulin-signaling.

Results:

Human with NAFLD and DIO-rats showed higher liver Plin2 expression than control group (P = 0.03, P = 0.008 respectively). Liver LAMP2A expression was lower in NAFLD-humans and DIO-rats than in SG operated and controls group (P = 0.003, P = 0.02). Insulin-signaling was significantly increased in the liver of human controls and SG-rats. Liver and monocytes from NAFLD-humans and DIO-rats showed an increased lipid accumulation and a decreased glycogen deposition compared to human control groups and SG-rats. Overexpression of Plin2 in hepatocytes reduced Akt-Ser473, GSK3α/β-Ser21/9 and FOXO1a-Thr24 (P = 0.008, P = 0.01, P = 0.03 respectively).

Conclusion:

We propose that obesity promotes liver Plin2 overexpression through inhibition of CMA, with consequent lipid droplets accumulation and impairment of hepatic insulin sensitivity. SG improves CMA with removal of Plin2 coating lipid droplets and promotes lipolysis and amelioration of hepatic insulin resistance.