Camptothecin activates SIRT1 to promote lipid catabolism through AMPK/FoxO1/ATGL pathway in C2C12 myogenic cells.

Camptothecin activates SIRT1 to promote lipid catabolism through AMPK/FoxO1/ATGL pathway in C2C12 myogenic cells. Arch Pharm Res. 2019 Apr 24;: Authors: Lo MC, Chen JY, Kuo YT, Chen WL, Lee HM, Wang SG Abstract Caloric restriction activates sirtuin 1 (SIRT1) and induces a variety of metabolic effects that are beneficial for preventing age-related disease. The present study screened a commercially available used drug library to develop small molecule activators of SIRT1 as therapeutics for treatment of metabolic disorders. Using an in vitro fluorescence assay, the cancer therapeutic camptothecin increased SIRT1 enzymatic activity by 5.5-fold, indicating it to be a potent SIRT1 activator. Camptothecin also elevated the nicotinamide adenine dinucleotide (NAD)+/NADH ratio and increased SIRT1 protein levels in differentiated C2C12 myogenic cells. Treatment of C2C12 myotubes with camptothecin increased phosphorylation of AMP-dependent kinase (AMPK) and acetyl-coenzyme A carboxylase, caused nuclear translocation and deacetylation of forkhead box O1 (FoxO1), increased transcription and protein expression of adipose triglyceride lipase (ATGL), decreased the amount of intracellular oil droplets, and significantly increased β-oxidation of fatty acids. These in vitro data were confirmed in vivo as camptothecin treatment of C57BL/6J mice reduced fat and plasma triglyceride levels. All of the above camptothecin-induced alterations were attenuated...
Source: Archives of Pharmacal Research - Category: Drugs & Pharmacology Authors: Tags: Arch Pharm Res Source Type: research