CDK6 inhibits de novo lipogenesis in white adipose tissues but not in the liver.
Nat Commun
; 15(1): 1091, 2024 Feb 05.
Article
in En
| MEDLINE
| ID: mdl-38316780
ABSTRACT
Increased de novo lipogenesis (DNL) in white adipose tissue is associated with insulin sensitivity. Under both Normal-Chow-Diet and High-Fat-Diet, mice expressing a kinase inactive Cyclin-dependent kinase 6 (Cdk6) allele (K43M) display an increase in DNL in visceral white adipose tissues (VAT) as compared to wild type mice (WT), accompanied by markedly increased lipogenic transcriptional factor Carbohydrate-responsive element-binding proteins (CHREBP) and lipogenic enzymes in VAT but not in the liver. Treatment of WT mice under HFD with a CDK6 inhibitor recapitulates the phenotypes observed in K43M mice. Mechanistically, CDK6 phosphorylates AMP-activated protein kinase, leading to phosphorylation and inactivation of acetyl-CoA carboxylase, a key enzyme in DNL. CDK6 also phosphorylates CHREBP thus preventing its entry into the nucleus. Ablation of runt related transcription factor 1 in K43M mature adipocytes reverses most of the phenotypes observed in K43M mice. These results demonstrate a role of CDK6 in DNL and a strategy to alleviate metabolic syndromes.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cyclin-Dependent Kinase 6
/
Lipogenesis
Limits:
Animals
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: