Adiporon Drives Tibetan Pig Adipocyte Thermogenesis Through Adipor2-Ampk Pathway

Aims: The Tibetan pig thrives on the Tibetan Plateau of China, showcasing remarkable cold resilience. However, the precise mechanisms underlying its adaptation to high-altitude cold environments remain elusive. Adiponectin, a hormone secreted by adipocytes, regulates energy metabolism. This study aimed to clarify the mechanism by which adiponectin triggers thermogenesis in the adipocytes of Tibetan pigs via the AdipoR2-AMPK pathway.Main methods: The experiments used adipocytes from the inguinal area of 20-day-old Tibetan piglets for AdipoRon administration, plasmid transfection, and siRNA transfection. The impact of AdipoRon on genes associated with thermogenesis, mitochondrial respiration, lipid synthesis, degradation, and fatty acid oxidation was investigated using RT-qPCR, Western Blot, CCK-8, Oil Red O staining, ATP assay, mitochondrial membrane potential assay, and Free Fatty Acid assay.Key findings: AdipoRon, When introduced as an exogenous agonist in vitro, greatly increased thermogenesis by stimulating the tricarboxylic acid cycle, glycolysis, and ATP production within the cells. Concurrently, thermogenesis-related genes and mitochondrial complexes I~III displayed increased expression, correlating with elevated mitochondrial potential, reduced free fatty acids, and enhanced fatty acid oxidation. In Tibetan pig adipocytes, overexpression of AdipoR2 was found to significantly enhance thermogenic metabolism compared to control. Conversely, inhibiting AdipoR2 yielded divergent outcomes. Notably, the overexpression of AdipoR2 and the administration of AdipoRon increased the expression of phosphoThr172 AMP-dependent kinase (AMPK) and phospho-Ser79 Acetyl-CoA carboxylase (ACC) proteins. Significance: AdipoRon modulates the activity and thermogenic process of beige adipocytes by activating the AMPK signaling pathway.