Adiponectin receptor agonist AdipoRon regulates glucose and lipid metabolism via PPARγ signaling pathway in hepatocytes of large yellow croaker (Larimichthys crocea).

Abstract

Activation of adiponectin receptors (AdipoRs) has been shown to regulate glucose and lipid metabolism in mammalian hepatocytes. However, much less is known for their roles in fish. The current study demonstrated that AdipoRon, a small-molecule activator of AdipoRs, modulated glucose and lipid metabolism in large yellow croaker. In hepatocytes of large yellow croaker, AdipoRon upregulated the mRNA expression of adipors and appl1, while increasing phosphorylation levels of AMPK and AKT. These changes indicate the activation of AdipoR-mediated signaling. Furthermore, AdipoRon promoted glucose uptake, increased intracellular glucose content, as well as upregulated genes involved in glycogen synthesis and glycolysis whereas downregulated gluconeogenesis-related genes. On the other hand, AdipoRon facilitated free fatty acid (FFA) absorption by increasing the expression of fatty acid transport genes (fat/cd36, fatp1, and fabp11). It also enhanced triglyceride (TG) synthesis, evidenced by increased triglyceride levels and upregulation of dgat2 and PPARγ, which is consistent with the effect of adiponectin (APN) in large yellow croaker. Additional evidence suggested that inhibition of PPARγ with GW9662 reduced the effects of AdipoRon on glucose uptake and lipid metabolism, indicating that PPARγ is a key mediator in these metabolic regulations. Overall, AdipoRon was found to modulate multiple metabolic processes in hepatocytes of large yellow croaker via PPARγ signaling pathway, and these findings suggested that AdipoRon might contribute to beneficial effects on metabolic homeostasis in teleosts.