Hypoxia-inducible factors (HIFs) are crucial to maintain oxygen homeostasis by regulating cellular metabolic adaptation under hypoxia conditions. Depletion of factor inhibiting HIF (FIH), an enzyme that negatively regulates the activity of the HIF-1α isoform, has been associated with reductions in hepatic steatosis and body mass in mice.
Tyrosine-protein phosphatase non-receptor type 1 (PTP1B) acts as a negative regulator of the insulin signaling pathway by dephosphorylating both the insulin receptor (IR) and the insulin receptor substrate, leading to insulin resistance, the most significant characteristic of type 2 diabetes.