Mitochondrial protein IF1 is a potential regulator of glucagon-like peptide (GLP-1) secretion function of the mouse intestine

• Main Authors: Ying Wang (Author), Jiaojiao Zhang (Author), Xinyu Cao (Author), Yaya Guan (Author), Shuang Shen (Author), Genshen Zhong (Author), Xiwen Xiong (Author), Yanhong Xu (Author), Xiaoying Zhang (Author), Hui Wang (Author), Jianping Ye (Author)
• Format: Book
• Published: Elsevier, 2021-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2211-3835; 10.1016/j.apsb.2021.02.002
• Keywords: GLP-1; ATPIF1; ANT2; L-cells; Mitophagy; Microbiota; Therapeutics. Pharmacology; RM1-950
• Source: Acta Pharmaceutica Sinica B, Vol 11, Iss 6, Pp 1568-1577 (2021)

IF1 (ATPIF1) is a nuclear DNA-encoded mitochondrial protein whose activity is inhibition of the F1Fo-ATP synthase to control ATP production. IF1 activity remains unknown in the regulation of GLP-1 activity. In this study, IF1 was examined in the diet-induced obese mice using the gene knockout (If1-KO) mice. The mice gained more body weight on a high fat diet without a change in food intake. Insulin tolerance was impaired, but the oral glucose tolerance was improved through an increase in GLP-1 secretion. The KO mice exhibited an improved intestine structure, mitochondrial superstructure, enhanced mitophagy, reduced apoptosis and decreased adenine nucleotide translocase 2 (ANT2) protein in the intestinal epithelial cells together with preserved gut microbiota. The data suggest that GLP-1 secretion was enhanced in the obese If1-KO mice to preserve glucose tolerance through a signaling pathway of ANT2/mitochondria/L-cells/GLP-1/insulin. IF1 is a potential mitochondrial target for induction of GLP-1 secretion in L-cells.