Novel targets of beta-TrCP cooperatively accelerate carbohydrate and fatty acid consumption
- Authors
- Joo, Hyun Jeong; D'Alessandro, Matthew; Oh, Gaeun; Han, Sora; Kim, Woo Jung; Chung, Ga Eun; Jang, Youjeong; Lee, Jung Bok; Lee, Choogon; Yang, Young
- Issue Date
- Mar-2024
- Publisher
- WILEY
- Keywords
- E3 ligase; energy homeostasis; metabolism; obesity; ubiquitination; beta-TrCP
- Citation
- JOURNAL OF CELLULAR PHYSIOLOGY, v.239, no.3
- Journal Title
- JOURNAL OF CELLULAR PHYSIOLOGY
- Volume
- 239
- Number
- 3
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/159839
- DOI
- 10.1002/jcp.31095
- ISSN
- 0021-9541
1097-4652
- Abstract
- 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.
- Files in This Item
-
Go to Link
- Appears in
Collections - 이과대학 > 생명시스템학부 > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.