MASLD/MASH and Insulin Resistance

High prevalence of obesity and type 2 diabetes worldwide have dramatically increased cases of metabolic dysfunction-associated steatotic liver disease (MASLD). As a significant proportion of patients with MASLD experience a state of hepatic inflammation (Metabolic dysfunction-associated steatohepatitis (MASH)) which can result in hepatic fibrosis, cirrhosis and eventually hepatocellular carcinoma, this spectrum of liver disorders represents a medical challenge. Although lifestyle changes have beneficial effects, efficient treatments to treat MASLD/MASH are lacking. Our aim is to find therapeutic targets notably regarding the signaling pathways of FGF21, GLP-1 receptor agonists and cytokines of the interleukin-1 family. Our research also focuses on the role of the intestinal microbiota and the enterohepatic axis in the occurrence and progression of MASLD/MASH.

RESEARCH AIMS

-        Understand the implication of the gut-liver axis in MASLD/MASH.

-        Better understand progression of MALSD/MASH.

-        Find new targets to treat MASLD/MASH and prevent/reverse hepatic fibrosis

CORE EXPERTISE

Phenotyping of genetically modified mice. Physiology, histology, gene expression analysis, western-blot, gut microbiota composition analysis.

SELECTED PUBLICATIONS

Somm E, Jornayvaz FR. Interleukin-18 in metabolism: from mice physiology to human diseases. Front Endocrinol (Lausanne). 2022;13:971745.

Somm E, Montandon SA, Loizides-Mangold U, Gaïa N, Lazarevic V, De Vito C, et al. The GLP-1R agonist liraglutide limits hepatic lipotoxicity and inflammatory response in mice fed a methionine-choline deficient diet. Transl Res. 2020;S1931-5244(20)30176-6.

Montandon SA, Somm E, Loizides-Mangold U, De Vito C, Dibner C, Jornayvaz FR. Multi-technique comparison of atherogenic and MCD NASH models highlights changes in sphingolipid metabolism. Sci Rep. 2019;9(1):16810.

Somm E, Jornayvaz FR. Fibroblast growth factor 15/19 - from basic functions to therapeutic perspectives. Endocr Rev. 2018;39:960–89.

Camporez JPG, Asrih M, Zhang D, Kahn M, Samuel VT, Jurczak MJ, et al. Hepatic insulin resistance and increased hepatic glucose production in mice lacking FGF21. J Endocrinol. 2015;226:207–17.

Research