Restoration of mRNA Expression of Solute Carrier Proteins in Liver of Diet-Induced Obese Mice by Metformin.

Abstract

Metformin (MET), the most common medicine for type 2 diabetes (T2DM), improves insulin sensitivity by targeting the liver, intestine and other organs. Its impact on expression of the solute carrier (Slc) transporter genes have not been reported in the mechanism of insulin sensitization. In this study, we examined Slc gene expression in the liver and colon of diet-induced obese (DIO) mice treated with MET by transcriptomic analysis. There were 939 differentially expressed genes (DEGs) in the liver of DIO mice vs lean mice, which included 34 Slc genes. MET altered 489 DEGs in the liver of DIO mice, in which 23 were Slc genes. Expression of 20 MET-responsive Slc DEGs was confirmed by qRT-PCR, in which 15 Slc genes were altered in DIO mice and their expressions were restored by MET, including Slc2a10, Slc2a13, Slc5a9, Slc6a14, Slc7a9, Slc9a2, Slc9a3, Slc13a2, Slc15a2, Slc26a3, Slc34a2, Slc37a1, Slc44a4, Slc51b and Slc52a3. While, there were only 97 DEGs in the colon of DIO mice with 5 Slc genes, whose expression was not restored by MET. The data suggest that more genes were altered in the liver over the colon by the high fat diet (HFD). There were 20 Slc genes with alteration confirmed in the liver of DIO mice and 15 of them were restored by MET, which was associated with improvement of insulin sensitivity and obesity. The restoration may improve the uptake of glucose, amino acids, mannose, fructose, 1,5-anhydro-D-glucitol and bumetanide in hepatocytes of the liver of DIO mice. The study provides new insight into the mechanism of metformin action in insulin sensitization and obesity.

• Authors: Jiamei Le, Yi Fu, Qiuqin Han, Xindong Wei, Houlin Ji, Yifan Chen, Qiuying Wang, Peixian Pi, Jilei Li, Xinjie Lin, Xiaoying Zhang, Yong Zhang, Jianping Ye
• Journal: Frontiers in endocrinology (Front Endocrinol (Lausanne)) Vol. 12 Pg. 720784 ( 2021) ISSN: 1664-2392 [Print] Switzerland
• PMID: 34659115 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Le, Fu, Han, Wei, Ji, Chen, Wang, Pi, Li, Lin, Zhang, Zhang and Ye.

Chemical References

• RNA, Messenger
• Solute Carrier Proteins
• Metformin
• Glucose

Topics

• Animals
• Diet, High-Fat
• Gene Expression Regulation (drug effects)
• Glucose (metabolism)
• Glucose Tolerance Test
• Hepatocytes (drug effects, metabolism, pathology)
• Insulin Resistance (genetics)
• Liver (drug effects, metabolism, pathology)
• Male
• Metformin (pharmacology, therapeutic use)
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Obesity (drug therapy, genetics, metabolism, pathology)
• RNA, Messenger (metabolism)
• Solute Carrier Proteins (drug effects, genetics, metabolism)