产热
产热素
褐色脂肪组织
谷氨酰胺
生物化学
化学
糖酵解
生物
内分泌学
内科学
脂肪组织
新陈代谢
氨基酸
医学
作者
Yuko Okamatsu‐Ogura,Masashi Kuroda,Rie Tsutsumi,Ayumi Tsubota,Masayuki Saito,Kazuhiro Kimura,Hiroshi Sakaue
标识
DOI:10.1016/j.metabol.2020.154396
摘要
BackgroundBrown adipose tissue (BAT) is a site of metabolic thermogenesis mediated by mitochondrial uncoupling protein 1 (UCP1) and represents a target for a therapeutic intervention in obesity. Cold exposure activates UCP1-mediated thermogenesis in BAT and causes drastic changes in glucose, lipid, and amino acid metabolism; however, the relationship between these metabolic changes and UCP1-mediated thermogenesis is not fully understood.MethodsWe conducted metabolomic and GeneChip array analyses of BAT after 4-h exposure to cold temperature (10 °C) in wild-type (WT) and UCP1-KO mice.ResultsCold exposure largely increased metabolites of the glycolysis pathway and lactic acid levels in WT, but not in UCP1-KO, mice, indicating that aerobic glycolysis is enhanced as a consequence of UCP1-mediated thermogenesis. GeneChip array analysis of BAT revealed that there were 2865 genes upregulated by cold exposure in WT mice, and 838 of these were upregulated and 74 were downregulated in UCP1-KO mice. Pathway analysis revealed the enrichment of genes involved in fatty acid (FA) β oxidation and triglyceride (TG) synthesis in both WT and UCP1-KO mice, suggesting that these metabolic pathways were enhanced by cold exposure independently of UCP1-mediated thermogenesis. FA and cholesterol biosynthesis pathways were enhanced only in UCP1-KO mice. Cold exposure also significantly increased the BAT content of proline, tryptophan, and phenylalanine amino acids in both WT and UCP1-KO mice. In WT mice, cold exposure significantly increased glutamine content and enhanced the expression of genes related to glutamine metabolism. Surprisingly, aspartate was almost completely depleted after cold exposure in UCP1-KO mice. Gene expression analysis suggested that aspartate was actively utilized after cold exposure both in WT and UCP1-KO mice, but it was replenished from intracellular N-acetyl-aspartate in WT mice.ConclusionsThese results revealed that cold exposure induces UCP1-mediated thermogenesis-dependent glucose utilization and UCP1-independent active lipid metabolism in BAT. In addition, cold exposure largely affects amino acid metabolism in BAT, especially UCP1-dependently enhances glutamine utilization. These results contribute a comprehensive understanding of UCP1-mediated thermogenesis-dependent and thermogenesis-independent metabolism in BAT.
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