Alleviation of hepatic insulin resistance and steatosis with NMN via improving endoplasmic reticulum-Mitochondria miscommunication in the liver of HFD mice

作者全名：Li, Yumeng; Tian, Xutong; Yu, Qian; Bao, Tongtong; Dai, Chao; Jiang, Liang; Niu, Kaimin; Yang, Jianying; Wang, Shujin; Wu, Xin

作者地址：[Li, Yumeng; Tian, Xutong; Yu, Qian; Bao, Tongtong; Wu, Xin] Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Tianjin, Peoples R China; [Dai, Chao; Wu, Xin] Chinese Acad Sci, Inst Subtrop Agr, CAS Key Lab Agroecol Proc Subtrop Reg, Changsha, Peoples R China; [Wang, Shujin] Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China; [Tian, Xutong; Yang, Jianying] Henan Univ Sci & Technol, Affiliated Hosp 1, Coll Clin Med, Med Coll, Luoyang, Peoples R China; [Jiang, Liang] ERA Biotechnol Shenzhen Co Ltd, Shenzhen 518115, Peoples R China; [Niu, Kaimin] Jiangxi Acad Sci, Inst Biol Resources, Nanchang, Peoples R China

通信作者：Wu, X (通讯作者)，Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Tianjin, Peoples R China.

来源：BIOMEDICINE & PHARMACOTHERAPY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001238621400001

JCR分区：Q1

影响因子：6.9

年份：2024

卷号：175

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Hepatic steatosis; Mitochondrial dysfunction; Endoplasmic reticulum stress; HFD mice; NMN

摘要：The interaction between endoplasmic reticulum (ER) and mitochondria has been shown to play a key role in hepatic steatosis during chronic obesity. beta-nicotinamide mononucleotide (NMN) has been reported to regulate obesity, however, its molecular mechanism at the subcellular level remains unclear. Here, NMN improved liver steatosis and insulin resistance in chronic high-fat diet (HFD) mice. RNA-seq showed that compared with the liver of HFD mice, NMN intervention enhanced fat digestion and absorption and stimulated the cholesterol metabolism signaling pathways, while impaired insulin resistance and the fatty acid biosynthesis signaling pathways. Mechanistically, NMN ameliorated mitochondrial dysfunction and ER oxidative stress in the liver of HFD mice by increasing hepatic nicotinamide adenine dinucleotide (NAD+) (P < 0.01) levels. This effect increased the contact sites (mitochondria-associated membranes [MAMs]) between ER and mitochondria, thereby promoting intracellular ATP (P < 0.05) production and mitigating lipid metabolic disturbances in the liver of HFD mice. Taken together, this study provided a theoretical basis for restoring metabolic dynamic equilibrium in the liver of HFD mice by increasing MAMs via the nutritional strategy of NMN supplementation.

基金机构：Tianjin Synthetic Biotechnology Inno-vation Capacity Improvement Project [TSBICIP-CXRC-031]; Basic Research Project for Provincial Research of Jiangxi Academy of Sciences [2022YJC2002]

基金资助正文：<B>Funding</B> This work was supported by Tianjin Synthetic Biotechnology Inno-vation Capacity Improvement Project (TSBICIP-CXRC-031) , and Basic Research Project for Provincial Research of Jiangxi Academy of Sciences (2022YJC2002) .