SOCS3 and Insulin resistance: In mouse model of insulin resistance induced by high-fat diet, liver-specific knockdown of FGF-21 resulted in increased glycogenolysis and gluconeogenesis by activating glucose-6-phosphatase and phosphoenolpyruvate carboxykinase via the Stat3/SOCS3 pathway, which ultimately led to exacerbation of hepatic insulin resistance [35].