Phosphorylation status of fetuin-A is critical for inhibition of insulin action and is correlated with obesity and insulin resistance
Artículo académico
Fetuin-A, a hepatokine associated with insulin resistance, obesity and incident type 2 diabetes, is shown to exist in both phosphorylated and dephosphorylated forms in circulation. However, studies on fetuin-A phosphorylation status in insulin resistant conditions and its functional significance, are limited. We demonstrate that serum phosphofetuin-A (Ser312) levels were significantly elevated in high-fat diet-induced obese mice, insulin resistant Zucker diabetic fatty rats, and in obese, insulin resistant individuals. Unlike serum total fetuin-A, serum phosphofetuin-A was associated with body weight, insulin, and markers of insulin resistance. To characterize potential mechanisms, fetuin-A was purified from Hep3B human hepatoma cells. Hep3B FetA was phosphorylated (Ser312), and inhibited insulin-stimulated glucose uptake and glycogen synthesis in L6GLUT4 myoblasts. Further, single (Ser312Ala) and double (Ser312Ala+Ser120Ala) phosphorylation-defective Fet-A mutants were without effect on glucose uptake and glycogen synthesis in L6GLUT4 myoblasts. Together, our studies demonstrate that phosphorylation status of fetuin-A (Ser312) is associated with obesity and insulin resistance, and raise the possibility that fetuin-A phosphorylation may play a role in regulation of insulin action.
