HNF1α Controls Liver Lipid Metabolism and Insulin Resistance via Negatively Regulating the SOCS-3-STAT3 Signaling Pathway

Figure 7

HNF1α inhibits steatosis through suppressing STAT3 in vivo. (a) Oil Red O staining showed that increased liver steatosis in HNF1α-/- mouse liver compared with WT HFD group. Treatment of NSC74859 in HNF1α-/- mice rescued them from severe steatosis. (b) Liver weight of HNF1α-/- mice were significantly higher than WT mice fed with HFD, treatment of NSC74859 decreased mouse liver weight. (c–e) Biochemical indicators showed that HNF1α deficiency increased triglyceride (TG), cholesterol (TC), and nonesterified fatty acid (NEFA) contents from the liver tissue. After treating the mice with NSC74859, the contents of TG, TC, and NEFA decreased significantly. (f, g) Serum fasting insulin levels were determined by ELISA, and homeostasis model assessment of insulin resistance (HOMA-IR) index was calculated as . –8 per group, at the 8th week. HNF1α defect mice were significantly higher than WT mice fed with HFD. After treating the mice with NSC74859, the insulin levels and the HOMA-IR index decreased significantly. (h) Western blot analysis showed that HNF1α deficiency increased the expression of SREBP-1c and phosphorylation of STAT3 and reduced the expressions of SOCS3 and PPARα and phosphorylation of IRS-1 and AKT. Treating HNF1α defect mice with NSC74859 reversed these protein expressions: NSC74859 inhibited the expression of SREBP-1c and promoted the expression of PPARα. All values are expressed as , –12 per group, , , and .

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