In conjunction with prior pertinent studies [36, 48–50, 52, 54–61], these results have implicated that HIF2α, unlike HIF1α, is not essential in PDGFRβ + cells to maintain WAT and systemic metabolic homeostasis in HFD-fed mice, suggesting that selective pharmacological targeting of HIF1α rather than HIF2α may represent an effective strategy to promote WAT metabolic health, and preserve hepatic and systemic energy balance in the context of obesity. Here, EPAS1 is linked to obesity due to melanocortin 4 receptor deficiency.