Initiation of hyperinsulinemia and hyperleptinemia is diet dependent in C57BL/6 mice

C57BL/6 female mice were fed high fat diets containing different types of carbohydrate (sucrose or corn starch) and contents of cholesterol (0.03 % or 1 %) to identify early metabolic changes leading to increases in leptin levels and eventual insulin resistance. Under identical dietary fat conditions, type of carbohydrate and cholesterol content contributed to the timing of leptin increases. Mice fed a high-fat, high-sucrose diet showed early (4 weeks) and robust increases in circulating insulin and leptin levels (2-fold and 5-fold, respectively). In contrast, mice fed this diet with added cholesterol or with sucrose substituted by corn starch led to marked delays (8-10 weeks) in the elevations of insulin and leptin, although body weight gains were nearly identical among test diet groups. Thus, sucrose in combination with saturated fat played a specific role in initiating early metabolic changes associated with elevated leptin and insulin levels. Because leptin levels were most reflective of changes in insulin, our data support a role for insulin in determining plasma leptin levels in mice.