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Clusterin overexpression protects against western diet-induced obesity and NAFLD.

ABSTRACT: Obesity is a significant risk factor for various metabolic diseases and is closely related to non-alcoholic fatty liver disease (NAFLD) characterized by inflammation and oxidative stress. Clusterin is a multi-functional protein that is up-regulated in the pathogenesis of various metabolic diseases, including obesity and NAFLD. Our previous studies indicated that hepatocyte-specific overexpression of clusterin alleviates methionine choline-deficient (MCD) diet-induced non-alcoholic steatohepatitis (NASH) by activating nuclear factor erythroid 2-related factor 2 (Nrf2). Here we generated transgenic mice with whole-body clusterin overexpression (wCLU-tg) and investigated the role of clusterin in Western diet-induced obesity and NAFLD. We confirmed that obesity parameters and the spectrum of NAFLD of wCLU-tg mice were improved compared to wild type mice. Contrarily, clusterin deficiency deteriorated metabolic disruptions. We also found that clusterin activates target molecules for obesity and NAFLD, namely Nrf2 and AMPK, suggesting that clusterin protects against Western diet-induced obesity and NAFLD by activating Nrf2 and AMPK.

SUBMITTER: Park JS

PROVIDER: S-EPMC7562726 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Clusterin overexpression protects against western diet-induced obesity and NAFLD.

Park Jin-Sung JS Lee Woon-Kyu WK Kim Hyeon Soo HS Seo Ji A JA Kim Dong-Hoon DH Han Hee Chul HC Min Bon-Hong BH

Scientific reports 20201015 1

Obesity is a significant risk factor for various metabolic diseases and is closely related to non-alcoholic fatty liver disease (NAFLD) characterized by inflammation and oxidative stress. Clusterin is a multi-functional protein that is up-regulated in the pathogenesis of various metabolic diseases, including obesity and NAFLD. Our previous studies indicated that hepatocyte-specific overexpression of clusterin alleviates methionine choline-deficient (MCD) diet-induced non-alcoholic steatohepatiti ...[more]

PMID: 33060605

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Dataset Information

Clusterin overexpression protects against western diet-induced obesity and NAFLD.

Publications

Clusterin overexpression protects against western diet-induced obesity and NAFLD.

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