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 lean 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 μg/mg vs. 28.0±3.3 μg/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 μg/mg, P<0.001; and 36.8±2.8 μg/mg vs. 13.2±2.2 μg/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 μg/mg vs. 22.6±5.0 μg/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.