Perspective Chapter: Targeting PTP1B for the Treatment of Steatosis – Insights from Viscosol’s Role in Insulin-Mediated Lipid Metabolism Regulation

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), involves excessive fat buildup in liver cells and is closely linked to insulin resistance, type 2 diabetes mellitus (T2DM), and dyslipidemia. This chapter discusses MASLD pathophysiology, focusing on disrupted lipid metabolism, inflammation, and the key role of protein tyrosine phosphatase 1B (PTP1B) in insulin signaling and metabolic balance. The high-fat diet (HFD) plus low-dose streptozotocin (STZ) mouse model mimics human T2DM and MASLD, showing hyperglycemia, lipid abnormalities, and liver fat accumulation. Viscosol, a flavonoid from Dodonaea viscosa, shows strong therapeutic potential as a PTP1B inhibitor. Given at 33 mg/kg intraperitoneally for 7 days, Viscosol improved insulin sensitivity by increasing insulin receptor (INSR), IRS1/2, PI3K, and AKT expression, and regulated lipid metabolism genes (SREBP1c, FAS, PPARγ). It lowered serum low density lipoprotein (LDL), very low-density lipoprotein (VLDL), and total cholesterol. Histology showed less liver fat, reduced fibrosis markers (α-SMA, TGF-β1), and decreased inflammation. Viscosol also boosted cholesterol efflux via ABCA1 and ApoA1 and lowered inflammatory cytokines (TNF-α, IL-6) and the oxidative stress marker FOXO1, restoring metabolic health. These results suggest Viscosol as a promising natural agent targeting PTP1B to treat insulin resistance, dyslipidemia, and hepatic steatosis in MASLD and T2DM. Further clinical studies are needed to confirm these effects in humans.