Diet and aging are linked to insulin resistance a major risk factor for a constellation of diseases including osteoporosis, Alzheimer’s disease and type 2 diabetes. However, the direct contribution of diet versus aging to these processes is not clear. Here we examined the long term consequences of chow versus high-fat-diet (HFD) on various health indices in C57BL6 mice. HFD resulted in significant glucose intolerance within 1 d of feeding and this was sustained for 6 months after which it began to resolve until complete resolution by 12 months on the diet. The resolution of glucose intolerance was due to a striking compensation by the pancreas as a result of beta cell proliferation. Preliminary studies indicate that this may be due to an unexpected stimulatory effect of leptin on insulin secretion. The HFD also caused marked deterioration in bone morphology and brain function, as measured by memory deficit and a change in the Amyloid Beta 40 to 42 ratio. The effect of aging per se on each of these parameters was mild compared to the effect of diet. We conclude that western style diets have profound deleterious effects on multiple organ systems and the effect of diet is much more potent than age alone.