Acute Elevated Resistin Exacerbates Mitochondrial Damage and Aggravates Liver Steatosis Through AMPK/PGC-1α Signaling Pathway in Male NAFLD Mice

Fengyun Wen; Zhuoyan Shi; Xiaoping Liu; Yuguang Tan; Lan Wei; Xuemin Zhu; Hui Zhang; Xiaohuan Zhu; Xiangmiao Meng; Weixia Ji; Mengting Yang; Zhaoxuan Lu

doi:10.1055/a-1293-8250

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2021; 53(02): 132-144
DOI: 10.1055/a-1293-8250

Endocrine Research

Acute Elevated Resistin Exacerbates Mitochondrial Damage and Aggravates Liver Steatosis Through AMPK/PGC-1α Signaling Pathway in Male NAFLD Mice

Fengyun Wen

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan, P. R. China

,

Zhuoyan Shi

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan, P. R. China

,

Xiaoping Liu

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan, P. R. China

,

Yuguang Tan

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan, P. R. China

,

Lan Wei

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan, P. R. China

,

Xuemin Zhu

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan, P. R. China

,

Hui Zhang

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan, P. R. China

,

Xiaohuan Zhu

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan, P. R. China

,

Xiangmiao Meng

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan, P. R. China

,

Weixia Ji

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan, P. R. China

,

Mengting Yang

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan, P. R. China

,

Zhaoxuan Lu

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan, P. R. China

› Author Affiliations

Abstract

Resistin was identified as a link between obesity and insulin resistance and is associated with many diseases in mice. Deciphering the related development and molecular mechanism is necessary for the treatment of these diseases. Previous studies have revealed that increased resistin levels are correlated with lipid accumulation and play a role in non-alcoholic fatty liver disease (NAFLD) development. However, the exact mechanisms underlying these processes remain unclear. To further clarify whether acute elevated resistin level exacerbated liver steatosis, a high-fat diet-induced NAFLD animal model was used and treated with or without resistin for 6 days. We discovered that resistin altered mitochondrial morphology, decreased mitochondrial content, and increased lipid accumulation in HFD mice. qRT-PCR and western blot analysis showed that acute elevated resistin significantly altered the gene expression of mitochondrial biogenesis and liver lipid metabolism molecules in HFD mice. Consequently, in vitro experiments verified that resistin reduced the mitochondrial content, impaired the mitochondrial function and increased the lipid accumulation of palmitate-treated HepG2 cells. Additionally, we demonstrated that resistin upregulated proinflammatory factors, which confirmed that resistin promoted the development of inflammation in NAFLD mice and palmitate-treated HepG2 cells. Signaling-transduction analysis demonstrated that acute elevated resistin aggravated liver steatosis through AMPK/PGC-1α pathway in male mice. This reveals a novel pathway through which lipogenesis is induced by resistin and suggests that maintaining mitochondrial homeostasis may be key to treatments for preventing resistin-induced NAFLD aggravation.

Key words

insulin resistance - diabetes - adipokines - obesity - metabolic syndrome - lipid metabolism

Full Text

References

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Supplementary Material

Supplementary Material