AdipoAI and AdipoRON activates different adiponectin subunits in different tissues.
Reports indicates that obesity may be related with liver dysfunction, (Marchesini, Moscatiello, Di Domizio, & Forlani, 2008) further, literature also suggests that metabolic or physiological status of liver are altered in obesity and in T2D pathology (De Silva et al., 2019). Therefore, considering all these factors the hepatic screening of the DIO mice models was performed which interestingly revealed that the AdipoAI group increased gene expression profiles for Ppargc1a, AdipoR2 and Ppara (Fig 4 A, B & C) with simultaneously decreased the expression of IL-6, INF-b, TNF-a (Fig F, G & H) a potent inflammatory biomarker. We further tested weather AdipoAI could result in phosphorylation of AMPK by performing immunoblotting and IHC staining of liver tissue treated with AdipoAI, AdipoRON and CMC (Fig 4 D & E). Immunostaining and protein expression against AMPK known to improves insulin sensitivity and glucose homeostasis (Coughlan, Valentine, Ruderman, & Saha, 2014) we observed increased and prominent Phosphorylation of AMPK in both AdipoAI and AdipoRON liver tissue (Fig 4 D&E). Further, H&E-stained images of AdipoAI group showed evenly populated hepatocytes with mostly normal cytoplasmic contents and architecture (Fig 4I). The CMC and AdipoRON group exhibited sporadic infiltration with disarranged hepatocytes (arrowhead) and diffuse fatty changes. The overall results suggest that AdipoAI can results in phosphorylation of AMPK and activation of adiponectin subunits with decrease in cytokine levels in liver.