Evidence that leptin contributes to intestinal cholesterol absorption in obese (ob/ob) mice and wild-type mice

In the present study, the effect of leptin on intestinal cholesterol absorption was investigated in C57 BL/6 OlaHsd Lep(ob)/Lep(ob) obese (ob/ob) mice and loan C57 BL/6 (wild-type) mice, Animals were treated either with or without recombinant leptin for 2 wk. Cholesterol absorption was measured by the constant isotope feeding method and indirectly by the ratio of, campesterol to cholesterol in serum, In ob/ob mice, cholesterol absorption was significantly higher compared to wild-type mice [83.4 +/- 2.3% (SD) vs. 77.6 +/- 1.5%, P < 0.01]. Treatment with leptin significantly reduced cholesterol absorption in both ob/ob and wild-type mice by 8,5 (P < 0.001) and 5.2% (P < 0.05), respectively. Serum concentrations of campesterol and the ratio of campesterol to cholesterol in ob/ob mice were significantly higher compared to wild-type mice (2.2 +/- 0.3 mg/dL vs, 1.2 +/- 0.3 mg/dL, P < 0.001; and 36.8 +/- 2.8 mug/mg vs. 2 8.0 +/- 3.3 mug/mg, P < 0.001). After treatment of ob/ob mice with leptin, concentrations of campesterol and its ratio to cholesterol were significantly lower (2.2 +/- 0.3 mg/dL vs. 1.0 +/- 0.2 mu g/mg, P < 0.001; and 36.8 +/- 2.8 mug/mg vs. 13.2 +/- 2.2 mug/mg, P < 0.001, respectively). In wild-type mice, the ratio of campesterol to cholesterol in serum was also significantly lower after treatment with leptin (28.0 +/- 3.3 mu g/mg vs. 22.6 +/- 5.0 mu g/mg, P < 0.05). A significant positive correlation (r= 0.701, P< 0.01) between cholesterol absorption and the ratio of campesterol to cholesterol in serum was found. It is concluded that leptin contributes to intestinal cholesterol absorption in ob/ob mice and lean wild-type mice.