In the present study, we have used our newly generated muscle-specific p62 gene rescue mice (p62-mRes) to demonstrate that p62 in muscle 1) increases muscle mass and strength during HFD-feeding, 2) improves glucose tolerance and insulin resistance without affecting body mass, 3) activates mTOR signaling and increases GLUT4 expression, and 4) retards the progression of NASH, a common of feature of the metabolic syndrome. The gene discussed is SLC2A4; the disease is Insulin resistance.