ScholarWorks@숙명여자대학교

초록

Cellular energy is primarily produced from glucose and fat through glycolysis and fatty acid oxidation (FAO) followed by the tricarboxylic acid cycle in mitochondria; energy homeostasis is carefully maintained via numerous feedback pathways. In this report, we uncovered a new master regulator of carbohydrate and lipid metabolism. When ubiquitin E3 ligase beta-TrCP2 was inducibly knocked out in beta-TrCP1 knockout adult mice, the resulting double knockout mice (DKO) lost fat mass rapidly. Biochemical analyses of the tissues and cells from beta-TrCP2 KO and DKO mice revealed that glycolysis, FAO, and lipolysis were dramatically upregulated. The absence of beta-TrCP2 increased the protein stability of metabolic rate-limiting enzymes including 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3), adipose triglyceride lipase (ATGL), carnitine palmitoyltransferase 1A (CPT1A), and carnitine/ acylcarnitine translocase (CACT). Our data suggest that beta-TrCP is a potential regulator for total energy homeostasis by simultaneously controlling glucose and fatty acid metabolism and that targeting beta-TrCP could be an effective strategy to treat obesity and other metabolic disorders.

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