artepillin-c and Metabolic-Syndrome

Artepillin C (APC), a cAMP-response element-binding (CREB)/CREB regulated transcription coactivator 2 (CRTC2) inhibitor isolated from Brazilian green propolis, can ameliorate metabolic syndrome in obese mice. Because the sensitivity and responsiveness of the body to the drug depend on the time of day and the circadian clock alignment, the optimal administration time of APC for desired efficacy in treating metabolic syndrome remains unclear. In this study, APC (20 mg/kg) or the vehicle was intraperitoneally injected into obese mice once daily for one or three weeks. The results of the insulin tolerance test, pyruvate tolerance test, and histological and biochemical assays showed that APC could improve whole-body glucose homeostasis and decrease hepatic lipid synthesis following a circadian rhythm. Further exploration of the underlying mechanism revealed that APC may disturb the diurnal oscillations of the expression of brain and muscle ARNT-like protein (BMAL1) in primary hepatocytes and the livers of the study subjects. Moreover, APC could inhibit hepatic BMAL1 expression by blocking the CREB/CRTC2 transcription complex. BMAL1 overexpression in primary hepatocytes or the livers of

Topics: Animals; ARNTL Transcription Factors; Circadian Rhythm; Gene Expression Regulation; Liver; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Obese; Transcription Factors