New insight into the mechanisms of ectopic fat deposition improvement after bariatric surgery
Authors: Stefan R Bornstein
Carla Giordano
Bruna Cerbelli
Giulia Angelini
Giulia Del Corpo
Anna Severino
Alfredo Genco
Lidia Castagneto Gissey
Melania Manco
Geltrude Mingrone
Andreas L Birkenfeld
Giovanni Casella
Nicola Basso
Journal: Scientific Reports (2019)
Discipline: Multidisciplinary
Keywords: Non-alcoholic fatty-liver disease (NAFLD); Bariatric surgery; Insulin resistance; Sleeve-gastrectomy (SG); Monocytes
Affiliations: Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy and Università Cattolica del S. Cuore, Rome, Italy., Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy., Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy., Research Unit for Multi-factorial Diseases, Obesity and Diabetes, Istituti di Ricovero e Cura a Carattere Scientifico, Bambino Gesù Children's Hospital, Rome, Italy., Department of Medicine III, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Germany., Paul Langerhans Institute Dresden of the Helmholtz Center Munich at University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany., Diabetes and Nutritional Sciences, King's College London, London, United Kingdom., Deutsches Zentrum für Diabetesforschung, DZD e.V., Neuherberg, Germany., Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy. .

Abstract:  Non-alcoholic fatty-liver disease (NAFLD) is frequent in obese patients and represents a major risk factor for the development of diabetes and its complications. Bariatric surgery reverses the hepatic features of NAFLD. However, its mechanism of action remains elusive. We performed a comprehensive analysis of the mechanism leading to the improvement of NAFLD and insulin resistance in both obese rodents and humans following sleeve-gastrectomy (SG). SG improved insulin sensitivity and reduced hepatic and monocyte fat accumulation. Importantly, fat accumulation in monocytes was well comparable to that in hepatocytes, suggesting that Plin2 levels in monocytes might be a non-invasive marker for the diagnosis of NAFLD. Both in vitro and in vivo studies demonstrated an effective metabolic regeneration of liver function and insulin sensitivity. Specifically, SG improved NAFLD significantly by enhancing AMP-activated protein kinase (AMPK) phosphorylation and chaperone-mediated autophagy (CMA) that translate into the removal of Plin2 coating lipid droplets. This led to an increase in lipolysis and specific amelioration of hepatic insulin resistance. Elucidating the mechanism of impaired liver metabolism in obese subjects will help to design new strategies for the prevention and treatment of NAFLD. 

Retracted: No

PubPeer comments:
 Fig 2I (rat liver) looks similar to the brighter, recentered and stretched FIG 4G (human liver) ![file] , 
 Maybe figure 1 C+D does not show liver but blood cells? Figure 1 G indicates 12 but not 15 rat**s** as indicated in the legend; there is no u00df-actin control for AMPK; Pearson or Spearman correlation coefficient would be more appropriate than B A plots. ![file] , 
 Excess weight (**kg**) does not match weight given in line 3. Methods say that `Bonferroniu2019s correction or Dunnu2019s Multiple Comparison test` have been applied although I do not find crude and corrected P values. ![file] ,