Novel targets of β-TrCP cooperatively accelerate carbohydrate and fatty acid consumption.
Hyun Jeong JooMatthew D'AlessandroGaeun OhSora HanWoo Jung KimGa Eun ChungYoujeong JangJung Bok LeeChoogon LeeYoung YangPublished in: Journal of cellular physiology (2023)
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 β-TrCP2 was inducibly knocked out in β-TrCP1 knockout adult mice, the resulting double knockout mice (DKO) lost fat mass rapidly. Biochemical analyses of the tissues and cells from β-TrCP2 KO and DKO mice revealed that glycolysis, FAO, and lipolysis were dramatically upregulated. The absence of β-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 β-TrCP is a potential regulator for total energy homeostasis by simultaneously controlling glucose and fatty acid metabolism and that targeting β-TrCP could be an effective strategy to treat obesity and other metabolic disorders.
Keyphrases
- fatty acid
- adipose tissue
- high fat diet induced
- insulin resistance
- type diabetes
- transcription factor
- metabolic syndrome
- electronic health record
- gene expression
- physical activity
- skeletal muscle
- blood glucose
- cell death
- body mass index
- blood pressure
- climate change
- tyrosine kinase
- binding protein
- artificial intelligence
- glycemic control