 Studies in rodent model show that loss of Jak3 results in increased body weight, basal systemic CLGI, compromised glycemic homeostasis, hyperinsulinemia, and early symptoms of liver steatosis.Lack of Jak3 also results in exaggerated symptoms of metabolic syndrome by western high-fat diet.Mechanistically, it is shown that Jak3 is essential for reduced expression and activation of toll like receptors (TLRs) in murine intestinal mucosa and human intestinal epithelial cells where Jak3 interacted with and activated p85, the regulatory sub-unit of the PI3K, through tyrosine phosphorylation of adapter protein insulin receptor substrate (IRS1).