2. Academic Validation
  3. Hepatic Leucine Carboxyl Methyltransferase 1 (LCMT1) contributes to high fat diet-induced glucose intolerance through regulation of glycogen metabolism

Hepatic Leucine Carboxyl Methyltransferase 1 (LCMT1) contributes to high fat diet-induced glucose intolerance through regulation of glycogen metabolism

  • J Nutr Biochem. 2023 Mar 22;109321. doi: 10.1016/j.jnutbio.2023.109321.
Jiao Mo 1,  Xinhang Wang 1,  Ningjing Liang 1,  Ning Zhang 1,  Yunqing Li 1,  Zhijian Zheng 1,  Qingqing Ao 1,  Yijie Wu 1,  Tingting Tang 1,  Simi Liao 1,  Yu Lei 1,  Huan Ding 1,  Bingxin Du 1,  Mei Feng 1,  Chengying Chen 2,  Qianqian Shi 1,  Lancheng Wei 1,  Yue Huang 3,  Cailing Lu 4,  Shen Tang 5,  Xiyi Li 6
Affiliations

Affiliations

  • 1 Department of Nutrition and Food Hygiene, School of Public Health, Guangxi Medical University, Nanning, 530021, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, 530021, China.
  • 2 School of Basic Medical Sciences, Guangxi Medical University, Nanning, 530021, China.
  • 3 Division of Medical Genetics, Department of Human Genetics, the David Geffen School of Medicine, The University of California-Los Angeles, Los Angeles, CA, USA.
  • 4 Department of Nutrition and Food Hygiene, School of Public Health, Guangxi Medical University, Nanning, 530021, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, 530021, China. Electronic address: lucailing78@gxmu.edu.cn.
  • 5 School of Basic Medical Sciences, Guangxi Medical University, Nanning, 530021, China. Electronic address: 958714333@qq.com.
  • 6 Department of Nutrition and Food Hygiene, School of Public Health, Guangxi Medical University, Nanning, 530021, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, 530021, China. Electronic address: xiyi.li2017@hotmail.com.
PMID: 36963730 DOI: 10.1016/j.jnutbio.2023.109321
Abstract

Impaired glucose regulation is one of the most important risk factors for type 2 diabetes mellitus (T2DM) and cardiovascular diseases, which have become a major public health issue worldwide. Dysregulation of carbohydrate metabolism in liver has been shown to play a critical role in the development of glucose intolerance but the molecular mechanism has not yet been fully understood. In this study, we investigated the role of hepatic LCMT1 in the regulation of glucose homeostasis using a liver-specific LCMT1 knockout mouse model. The hepatocyte-specific deletion of LCMT1 significantly upregulated the hepatic glycogen synthesis and glycogen accumulation in liver. We found that the liver-specific knockout of LCMT1 improved high fat diet-induced glucose intolerance and Insulin resistance. Consistently, the high fat diet-induced downregulation of Glucokinase (GCK) and other important glycogen synthesis genes were reversed in LCMT1 knockout liver. In addition, the expression of GCK was significantly upregulated in MIHA cells treated with siRNA targeting LCMT1 and improved glycogen synthesis. In this study, we provided evidences to support the role of hepatic LCMT1 in the development of glucose intolerance induced by high fat diet and demonstrated that inhibiting LCMT1 could be a novel therapeutic strategy for the treatment of glucose metabolism disorders.

Keywords

HFD; LCMT1; glucokinase; glucose homeostasis; liver.

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