AUTHOR=Le Jiamei , Fu Yi , Han Qiuqin , Wei Xindong , Ji Houlin , Chen Yifan , Wang Qiuying , Pi Peixian , Li Jilei , Lin Xinjie , Zhang Xiaoying , Zhang Yong , Ye Jianping 

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

JOURNAL=Frontiers in Endocrinology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.720784

DOI=10.3389/fendo.2021.720784

ISSN=1664-2392

ABSTRACT=<p>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 (<italic>Slc</italic>) transporter genes have not been reported in the mechanism of insulin sensitization. In this study, we examined <italic>Slc</italic> 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 <italic>vs</italic> lean mice, which included 34 <italic>Slc</italic> genes. MET altered 489 DEGs in the liver of DIO mice, in which 23 were <italic>Slc</italic> genes. Expression of 20 MET-responsive <italic>Slc</italic> DEGs was confirmed by qRT-PCR, in which 15 <italic>Slc</italic> genes were altered in DIO mice and their expressions were restored by MET, including <italic>Slc2a10</italic>, <italic>Slc2a13</italic>, <italic>Slc5a9, Slc6a14</italic>, <italic>Slc7a9</italic>, <italic>Slc9a2</italic>, <italic>Slc9a3</italic>, <italic>Slc13a2</italic>, <italic>Slc15a2</italic>, <italic>Slc26a3</italic>, <italic>Slc34a2</italic>, <italic>Slc37a1</italic>, <italic>Slc44a4</italic>, <italic>Slc51b</italic> and <italic>Slc52a3</italic>. While, there were only 97 DEGs in the colon of DIO mice with 5 <italic>Slc</italic> 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 <italic>Slc</italic> 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.</p>