Genetic disruption of protein phosphatase 5 in mice prevents high-fat diet feeding-induced weight gain

The role of serine/threonine protein phosphatase 5 (PP5) in the development of obesity and insulin resistance associated with high-fat diet-feeding (HFD) was examined using PP5-deficient mice (Ppp5c(-/-)). Despite similar caloric intake, Ppp5c(-/-) mice on HFD gained markedly less weight and did not accumulate visceral fat compared to wild-type littermates (Ppp5c(+/+)). On a control diet, Ppp5c(-/-) mice had markedly improved glucose control compared to Ppp5c(+/+) mice, an effect diminished by HFD. However, even after 10 weeks of HFD glucose control in Ppp5c(-/-) mice was similar to that observed in Ppp5c(+/+) mice on the control diet. Thus, PP5 deficiency confers protection against HFD-induced weight gain in mice.