MARKED HYPERLEPTINEMIA AFTER HIGH-FAT DIET ASSOCIATED WITH SEVERE GLUCOSE-INTOLERANCE IN MICE

We asked whether the likelihood for mice of the C57BL/6J strain to dev elop glucose intolerance when fed a high-fat diet is related to the in crease in circulating levels of leptin or free fatty acids (FFA). We t herefore administered a high-fat diet (58% fat) or a control diet (11% fat) for 1.5 years. NMRI mice were used as a more glucose-tolerant co ntrol group. After a high-fat diet, the area under the glucose curve f ollowing an intraperitoneal glucose challenge (1g/kg) increased more m arkedly in C57BL/6J mice (by 42 +/- 8%) than in NMRI mice (by 21 +/- 3 %, P = 0.007). Plasma levels of insulin, leptin and FFA increased in b oth strains of mice, whereas plasma glucose levels were elevated after the high-fat diet only in C57BL/6J mice. The slope of the relationshi p between body weight and plasma leptin was higher in C57BL/6J mice th an in NMRI mice, suggesting leptin insensitivity. Circulating leptin c orrelated to circulating insulin in both strains of mice, whereas plas ma FFA correlated to plasma insulin in NMRI mice but not in C57BL/6J m ice. These correlations remained significant after adjustment for body weight. The results show that elevated leptin and FFA levels evolve a fter high-fat feeding in mice, in conjunction with evolvement of gluco se intolerance and hyperglycemia.