2. Academic Validation
  3. BACH1 controls hepatic insulin signaling and glucose homeostasis in mice

BACH1 controls hepatic insulin signaling and glucose homeostasis in mice

  • Nat Commun. 2023 Dec 21;14(1):8428. doi: 10.1038/s41467-023-44088-z.
Jiayu Jin # 1,  Yunquan He # 1,  Jieyu Guo # 1,  Qi Pan 1,  Xiangxiang Wei 1,  Chen Xu 2,  Zhiyuan Qi 1,  Qinhan Li 1,  Siyu Ma 1,  Jiayi Lin 1,  Nan Jiang 1,  Jinghua Ma 1,  Xinhong Wang 1,  Lindi Jiang 1,  Qiurong Ding 3,  Elena Osto 4,  Xiuling Zhi 5,  Dan Meng 6
Affiliations

Affiliations

  • 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • 2 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • 3 CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • 4 Division of Physiology and Pathophysiology, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria.
  • 5 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. zhixiuling@fudan.edu.cn.
  • 6 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. dmeng@fudan.edu.cn.
  • # Contributed equally.
PMID: 38129407 DOI: 10.1038/s41467-023-44088-z
Abstract

Hepatic Insulin resistance is central to the metabolic syndrome. Here we investigate the role of BTB and CNC homology 1 (BACH1) in hepatic Insulin signaling. BACH1 is elevated in the hepatocytes of individuals with obesity and patients with non-alcoholic fatty liver disease (NAFLD). Hepatocyte-specific Bach1 deletion in male mice on a high-fat diet (HFD) ameliorates hyperglycemia and Insulin resistance, improves glucose homeostasis, and protects against steatosis, whereas hepatic overexpression of Bach1 in male mice leads to the opposite phenotype. BACH1 directly interacts with the protein-tyrosine Phosphatase 1B (PTP1B) and the Insulin Receptor β (IR-β), and loss of BACH1 reduces the interaction between PTP1B and IR-β upon Insulin stimulation and enhances Insulin signaling in hepatocytes. Inhibition of PTP1B significantly attenuates BACH1-mediated suppression of Insulin signaling in HFD-fed male mice. Hepatic BACH1 knockdown ameliorates hyperglycemia and improves Insulin sensitivity in diabetic male mice. These results demonstrate a critical function for hepatic BACH1 in the regulation of Insulin signaling and glucose homeostasis.

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