2562-P: Therapeutic Potential of Molybdenum Disulfide Nanoflower and Pyrroloquinoline Quinone in Metabolic Regulation

Introduction and Objective: Metabolic dysregulation is one of the most prevalent endocrine health issues worldwide. Even though these conditions are raising global health burden, current therapeutic approaches are inadequate. In this perspective, mitochondrial biogenesis is significantly disrupted in metabolic dysregulation. We have shown before that molybdenum disulfide (MoS2) nanoflower and pyrroloquinoline quinone (PQQ) have potential to stimulate mitochondrial biogenesis in vitro primarily. Here, we investigated the efficacy of MoS2 nanoflower in combination with PQQ in ameliorating high-fat diet (HFD)-induced metabolic dysregulation in vivo. Methods: Six-week-old male C57BL/6 mice were fed HFD for 22 wks (n=5/group). Mice were randomized into 4 groups, and following regimens were given for 5 wks: 1) HFD, 2) PQQ pretreatment for 6 wks followed by MoS2, 3) PQQ concurrently with MoS2, 4) PQQ-conjugated MoS2. PQQ (20 mg/kg) was given orally once daily while MoS2 (5 mg/kg, i.v.) was administered once weekly. Body composition was assessed using EchoMRI at 26 wks. Glucose and insulin tolerance tests were performed at 27 wks. Results: We observed a significant decrease in body weight (BW) and fasting blood glucose (FBG) in PQQ concurrently with MoS2 (p<0.001) so does the PQQ pretreatment group (p<0.01), and PQQ-MoS2 conjugate group (p<0.05) when compared to HFD. PQQ concurrently with MoS2 also exhibited significant decrease in BW (p<0.05) and FBG (p<0.001) when compared to PQQ pretreatment group. In addition, glucose intolerance, and insulin resistance were also significantly reduced in both PQQ concurrently with MoS2 and PQQ pretreatment group (p<0.05). Furthermore, EchoMRI showed a significant shift towards increased lean mass in both PQQ concurrently with MoS2 (p<0.001) and PQQ pretreatment group (p<0.05). Conclusion: Our findings demonstrate that concurrent administration of PQQ with MoS2 treatment may serve as a potent therapeutic regimen for the treatment of diet-induced metabolic dysregulation. Disclosure S. Venkategowda: None. N. Shree: None. J. Soukar: None. A.K. Gaharwar: None. M. Choudhury: None.