An Artemisia scoparia Extract and Rosiglitazone Have Distinct but Overlapping Effects on Adipocyte Function

OBJECTIVE: An Artemisia scoparia extract (SCO) has been shown to enhance adipocyte function, improve insulin sensitivity, and regulate lipolysis. We evaluated the actions of SCO and rosiglitazone (ROSI) in adipocytes, focusing on PPARγ's role in their regulation. METHODS: We assessed PPARγ activation by measuring its half-life and the PPAR-dependent transcription of a luciferase reporter. We measured glycerol release from adipocytes with siRNA gene silencing or pharmacological inhibition of PPARγ. Immunoblotting was used to detect adiponectin and protein disulfide isomerase (PDI); transcriptional effects in SCO- and ROSI-treated cells were compared by RNA-seq. RESULTS: ROSI and SCO both enhanced PPARγ degradation, a hallmark of ligand-induced activation. PPARγ transcriptional activity was induced in three cell types by ROSI, but in only one by SCO. PPARγ knockdown reversed the antilipolytic effects of both SCO and ROSI, while pharmacological inhibition only reversed the effect of ROSI. SCO treatment, but not ROSI, produced reduction-resistant adiponectin multimers and high-molecular-weight complexes of PDI. Transcriptional changes were more pronounced with ROSI than SCO, although the affected pathways were largely overlapping. CONCLUSIONS: SCO is a context-dependent PPARγ agonist with unique effects on redox-dependent protein multimerization. Transcriptional profiling indicates that SCO acts as a partial or selective PPARγ agonist.