Based on the hypoxia-induced feedback loop, HFD induced a state of relative hypoxia, resulting in the accumulation of miR-210 and subsequently the decreased GPD1L. On the contrary, GPD1L was found to be upregulated in obese subjects in response to weight loss and maintenance induced by LCD, because during LCD the state of relative hypoxia was attenuated, resulting in the decreased miR-210 and subsequently the increased GPD1L. The increased GPD1L inhibited HIF-1α activity in adipose tissue, leading to reduction in obesity and insulin resistance. Here, GPD1L is linked to obesity due to melanocortin 4 receptor deficiency.