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Sci Rep. 2017 Jul 13;7(1):5274. doi: 10.1038/s41598-017-05349-2.

Vertical sleeve gastrectomy reverses diet-induced gene-regulatory changes impacting lipid metabolism.

Author information

1
Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, Duarte, CA, USA.
2
Irell & Manella Graduate School of Biological Sciences, City of Hope, Duarte, CA, USA.
3
Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, Duarte, CA, USA. tianjypaper@163.com.
4
Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, China National Research Center for Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. tianjypaper@163.com.
5
Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, Duarte, CA, USA. dschones@coh.org.
6
Irell & Manella Graduate School of Biological Sciences, City of Hope, Duarte, CA, USA. dschones@coh.org.
7
Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, Duarte, CA, USA. WHuang@coh.org.
8
Irell & Manella Graduate School of Biological Sciences, City of Hope, Duarte, CA, USA. WHuang@coh.org.

Abstract

Vertical sleeve gastrectomy (VSG) produces sustainable weight loss, remission of type 2 diabetes (T2D), and improvement of nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanisms underlying the metabolic benefits of VSG have remained elusive. According to our previous results, diet-induced obesity induces epigenetic modifications to chromatin in mouse liver. We demonstrate here that VSG in C57BL/6J wild-type male mice can reverse these chromatin modifications and thereby impact the expression of key metabolic genes. Genes involved in lipid metabolism, especially omega-6 fatty acid metabolism, are up-regulated in livers of mice after VSG while genes in inflammatory pathways are down-regulated after VSG. Consistent with gene expression changes, regulatory regions near genes involved in inflammatory response displayed decreased chromatin accessibility after VSG. Our results indicate that VSG induces global regulatory changes that impact hepatic inflammatory and lipid metabolic pathways, providing new insight into the mechanisms underlying the beneficial metabolic effects induced by VSG.

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