FAM13A Represses AMPK Activity and Regulates Hepatic Glucose and Lipid Metabolism

作者：Lin, Xin^*; Liou, Yae-Huei; Li, Yujun; Gong, Lu; Li, Yan; Hao, Yuan; Pham, Betty; Xu, Shuang; Jiang, Zhiqiang; Li, Lijia; Peng, Yifan; Qiao, Dandi; Lin, Honghuang; Liu, Pengda; Wei, Wenyi; Zhang, Guo; Lee, Chih-Hao; Zhou, Xiaobo^*

来源：iScience, 2020, 23(3): 100928.

DOI：10.1016/j.isci.2020.100928

• DIET-INDUCED OBESITY
• ACTIVATION
• INSULIN
• ADIPOSE
• STEATOSIS
• VARIANTS
• DISEASE
• RISK
• LINK

Obesity commonly co-exists with fatty liver disease with increasing health burden worldwide. Family with Sequence Similarity 13, Member A (FAM13A) has been associated with lipid levels and fat mass by genome-wide association studies (GWAS). However, the function of FAM13A in maintaining metabolic homeostasis in vivo remains unclear. Here, we demonstrated that rs2276936 in this locus has allelic-enhancer activity in massively parallel reporter assays (MPRA) and reporter assay. The DNA region containing rs2276936 regulates expression of endogenous FAM13A in HepG2 cells. In vivo, Fam13a(-/-) mice are protected from high-fat diet (HFD)-induced fatty liver accompanied by increased insulin sensitivity and reduced glucose production in liver. Mechanistically, loss of Fam13a led to the activation of AMP-activated protein kinase (AMPK) and increased mitochondrial respiration in primary hepatocytes. These findings demonstrate that FAM13A mediates obesity-related dysregulation of lipid and glucose homeostasis. Targeting FAM13A might be a promising treatment of obesity and fatty liver disease.

• 单位
  1; Huazhong University of Science and Technology