The Role of Brown Adipose Tissue in the Development and Treatment of
                    Nonalcoholic Steatohepatitis: An Exploratory Gene Expression Study in
                    Mice

Toon J.I. De Munck; Pan Xu; Brechtje L.J. Vanderfeesten; Montserrat Elizalde; Ad A.M. Masclee; Frederik Nevens; David Cassiman; Frank G. Schaap; Daisy M.A.E. Jonkers; Jef Verbeek

doi:10.1055/a-1301-2378

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2020; 52(12): 869-876
DOI: 10.1055/a-1301-2378

Endocrine Research

The Role of Brown Adipose Tissue in the Development and Treatment of Nonalcoholic Steatohepatitis: An Exploratory Gene Expression Study in Mice

Toon J.I. De Munck‡

¹Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands

²School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands

,

Pan Xu‡

¹Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands

²School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands

,

Brechtje L.J. Vanderfeesten

¹Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands

,

Montserrat Elizalde

²School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands

,

Ad A.M. Masclee

¹Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands

²School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands

,

Frederik Nevens

³Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium

,

David Cassiman

³Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium

,

Frank G. Schaap

²School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands

⁴Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands

⁵Department of General, Visceral and Transplantation Surgery, RWTH University Hospital Aachen, Aachen, Germany

,

Daisy M.A.E. Jonkers

¹Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands

²School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands

,

Jef Verbeek

³Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium

› Author Affiliations

Abstract

Brown adipose tissue (BAT) might be a beneficial mediator in the development and treatment of nonalcoholic steatohepatitis (NASH). We aim to evaluate the gene expression of BAT activity-related genes during the development and the dietary and surgical treatment of NASH. BAT was collected from male C57BL/6J mice that received a high fat-high sucrose diet (HF-HSD) or a normal chow diet (NCD) for 4 and 20 weeks (n=8–9 per dietary group and timepoint) and from mice that underwent dietary intervention (return to NCD) (n=8), roux-en-y gastric bypass (RYGB) (n=6), or sham procedure (n=6) after 12 weeks HF-HSD. Expression of BAT genes involved in lipid metabolism (Cd36 and Cpt1b; p<0.05) and energy expenditure (Ucp1 and Ucp3; p<0.05) were significantly increased after 4 weeks HF-HSD compared with NCD, whereas in the occurrence of NASH after 20 weeks HF-HSD no difference was observed. We observed no differences in gene expression regarding lipid metabolism or energy expenditure at 8 weeks after dietary intervention (no NASH) compared with HF-HSD mice (NASH), nor in mice that underwent RYGB compared with SHAM. However, dietary intervention and RYGB both decreased the BAT gene expression of inflammatory cytokines (Il1b, Tnf-α and MCP-1; p<0.05). Gene expression of the batokine neuregulin 4 was significantly decreased after 20 weeks HF-HSD (p<0.05) compared with NCD, but was restored by dietary intervention and RYGB (p<0.05). In conclusion, BAT is hallmarked by dynamic alterations in the gene expression profile during the development of NASH and can be modulated by dietary intervention and bariatric surgery.

Key words

nonalcoholic fatty liver disease, NAFLD, Nrg4, Ucp1, obesity

Full Text

References

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Supplementary Material

Supplementary Material