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Chaperonin counteracts diet-induced non-alcoholic fatty liver disease by aiding sirtuin 3 in the control of fatty acid oxidation – published online 24/01/2023

Weng graphical abstract

Shao-Wen Weng, Jian-Ching Wu, Feng-Chih Shen, Yen-Hsiang Chang, Yu-Jih Su, Wei-Shiung Lian, Ming-Hong Tai, Chia-Hao Su, Jiin-Haur Chuang, Tsu-Kung Lin, Chia-Wei Liou, Tian-Huei Chu, Ying-Hsien Kao, Feng-Sheng Wang, Pei-Wen Wang

Heat shock protein 60 (HSP60) is a mitochondrial chaperonin that plays an important role in escorting unfolded proteins. Mice deficient in HSP60 develop mitochondrial dysfunction and insulin resistance; however, the biological role of this chaperonin in nutrient metabolism and the development of non-alcoholic fatty liver disease (NAFLD) remains unclear. In this issue, Wang et al ( report that HSP60 deficiency was correlated with severe steatosis in human NAFLD biopsies. In contrast, transgenic mice overexpressing Hsp60 (Hsp60-Tg) developed less body fat, showed amelioration of dyslipidaemia, hepatic steatosis and M1/M2 macrophage dysregulation and exhibited lower levels of insulin resistance than wild-type mice when fed a high-fat diet. The respiratory quotient profile indicated that fat in Hsp60-Tg mice may be metabolised to meet energy demands. The authors demonstrate that, mechanistically, HSP60 promoted fatty acid oxidation by preserving sirtuin 3 (SIRT3)/AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor α (PPARα) signalling. The authors conclude that gain of mitochondrial HSP60 function may be a promising avenue for the development of therapeutic interventions for NAFLD and type 2 diabetes.

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