2. Academic Validation
  3. The S100 calcium-binding protein A6 plays a crucial role in hepatic steatosis by mediating lipophagy

The S100 calcium-binding protein A6 plays a crucial role in hepatic steatosis by mediating lipophagy

  • Hepatol Commun. 2023 Aug 31;7(9):e0232. doi: 10.1097/HC9.0000000000000232.
Qian Du 1 2,  Tingting Zhu 3,  Guorong Wen 2,  Hai Jin 2,  Jiaxing An 2,  Jingyu Xu 2,  Rui Xie 2,  Jiaxing Zhu 2,  Xiaoxu Yang 2,  Ting Zhang 2,  Qi Liu 2,  Shun Yao 2,  Xingyue Yang 2,  Biguang Tuo 2 4,  Xiong Ma 1
Affiliations

Affiliations

  • 1 Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China.
  • 2 Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, P.R. China.
  • 3 School of Medicine, Guizhou University, Guiyang, Guizhou, China.
  • 4 The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China.
PMID: 37655980 DOI: 10.1097/HC9.0000000000000232
Abstract

Background: S100 calcium-binding protein A6 (S100A6) is a calcium-binding protein that is involved in a variety of cellular processes, such as proliferation, Apoptosis, and the cellular response to various stress stimuli. However, its role in NAFLD and associated metabolic diseases remains uncertain.

Methods and results: In this study, we revealed a new function and mechanism of S100A6 in NAFLD. S100A6 expression was upregulated in human and mouse livers with hepatic steatosis, and the depletion of hepatic S100A6 remarkably inhibited lipid accumulation, Insulin resistance, inflammation, and obesity in a high-fat, high-cholesterol (HFHC) diet-induced murine hepatic steatosis model. In vitro mechanistic investigations showed that the depletion of S100A6 in hepatocytes restored lipophagy, suggesting S100A6 inhibition could alleviate HFHC-induced NAFLD. Moreover, S100A6 liver-specific ablation mediated by AAV9 alleviated NAFLD in obese mice.

Conclusions: Our study demonstrates that S100A6 functions as a positive regulator of NAFLD, targeting the S100A6-lipophagy axis may be a promising treatment option for NAFLD and associated metabolic diseases.

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