| Monocarboxylate transporter 1 in the liver modulates high-fat diet-induced obesity and hepatic steatosis in mice |
| 論文作者 |
Luo, XM; Li, ZX; Chen, LL; Zhang, XH; Zhu, XY; Wang, ZA; Chen, Y |
| 期刊/會議名稱 |
METABOLISM-CLINICAL AND EXPERIMENTAL |
| 論文年度 |
2023 |
| 論文類別 |
Article |
| 摘要 |
Background: The monocarboxylate transporter 1 (MCT1) is a member of the MCT family and is implicated in the transport of lactate and a few other monocarboxylates across the cell membrane. How hepatic MCT1 regulates the metabolic functions of the body is currently unknown.Methods: The functions of hepatic MCT1 on metabolism were analyzed using a mouse model with liver-specific deletion of Slc16a1 that encodes MCT1. Obesity and hepatosteatosis of the mice were induced by high-fat diet (HFD). The function of MCT1 on lactate transport was analyzed by measuring lactate level in hepatocytes and mouse liver. Degradation and polyubiquitination of PPAR & alpha; protein were investigated by biochemical methods.Results: Hepatic deletion of Slc16a1 aggravated high-fat diet (HFD)-induced obesity in female mice, but not in male mice. However, the increased adiposity in Slc16a1-deleted mice was not associated with obvious reductions in metabolic rate and activity. The lactate level of the liver was significantly increased by Slc16a1 deletion in the female mice under HFD condition, suggesting that MCT1 mainly mediated the efflux of lactate in hepatocytes. Deficiency of MCT1 in the liver aggravated HFD-induced hepatic steatosis in both female and male mice. Mechanistically, deletion of Slc16a1 was associated with reduced expressions of genes involved in fatty acid oxidation (FAO) in the liver. The degradation rate and polyubiquitination of PPAR & alpha; protein were enhanced by Slc16a1 deletion. Blocking the MCT1 function elevated the interaction of PPAR & alpha; with an E3 ubiquitin ligase HUWE1.Conclusions: Our findings suggested that the enhanced polyubiquitination and degradation of PPAR & alpha; upon Slc16a1 deletion likely contributes to the reduced expression of FAO-related genes and aggravation of HFDinduced hepatic steatosis. |
| 卷 |
143 |
| 影響因子 |
9.8 |
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