Supplementation of pyrroloquinoline quinone with atorvastatin augments mitochondrial biogenesis and attenuates low grade inflammation in obese rats

Mitochondrial dysfunction and Inflammation play a significant role in the manifestation of the co-morbidities of obesity. The study deciphered the impact of Pyrroloquinoline quinone (PQQ) per se and with Atorvastatin (ATS) on high fat, 10% fructose diet (HFFD) induced obese rats expressing low-grade inflammation, dyslipidemia, and mitochondrial dysfunction. HFFD was fed for 10 weeks followed by treatment for 5 weeks with ATS 10 or 20 mg/kg, PQQ 10 or 20 mg/kg, p.o. per se or their combinations. The impact on blood glucose, lipid profile and serum insulin, TNF-alpha, IL-1 beta, IL-18, IL-6 was estimated. Gene and protein expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC 1 alpha), Sirtuin 1 (SIRT1), Mitochondrial transcriptional factor A (TFAM) and augmented mitochondrial DNA (mtDNA), NOD like receptor protein 3 (NLRP3) and Caspase 1 was assessed. Rats receiving PQQ and ATS revealed significant decrease in body weights, anthropometric parameter, and adipose tissue vis-a-vis positive control. PQQ alone and with ATS improved glucose tolerance, lipid profile, insulin indices and lowered serum levels of inflammatory cytokines IL-18, IL-1 beta, TNF-alpha and IL-6 along with a rise in adiponectin. PQQ supplementation with ATS upregulated the mRNA expression of PGC 1 alpha, SIRT1, TFAM and augmented mtDNA while downregulating inflammatory markers NLRP3 and Caspase 1. PQQ supplementation with atorvastatin holds therapeutic promise to effectively combat mitochondrial dysfunction and chronic low-grade inflammation in obesity.