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.