Intestinal transit time is decreased in leptin-deficient obese mice

Abstract

Background. Obesity is associated with multiple comorbidities, altered leptin metabolism, and increased intestinal absorption of nutrients. We have recently demonstrated that leptin-deficient (Lep ob) obese mice have increased ileal sucrase activity resulting in greater absorption of carbohydrate than lean controls. We have also demonstrated altered in vitro jejunal responses to cholecystokinin in leptin-deficient obese mice. Leptin-deficiency has also previously been shown to increase gastric emptying, but its influence on intestinal transit time is unknown. Therefore, we hypothesized that leptin deficiency would alter intestinal transit time. Methods. Gastric emptying and intestinal transit time experiments were performed in 12- to 14-week-old leptin-deficient ( Lep ob ) obese mice ( n = 10) and C57Bl/6J ( n = 10) lean control mice. Fluorescent-labeled liquid dextran (200 μL of 25 mg/4 mL) was gavaged into the stomach and intestine was harvested after 1 h. The contents of the stomach and entire small intestine were divided into 10 equal parts, including the cecum and colon. The fluorescence distributed along the gastrointestinal tract was obtained. Percentage gastric emptying was calculated as the amount of diet gavaged divided by the amount remaining. The geometric center was calculated as the sum of the % fluorescence per segment × segment number. Results. Data were analyzed by Student’s t-test and are presented in the table. Conclusions. These data suggest that leptin-deficiency results in (1) increased gastric emptying and (2) decreased intestinal transit time. Therefore, we conclude that decreased intestinal time transit time in leptin-deficient obese mice may contribute to enhanced nutrient absorptive efficiency commonly observed in obesity. TABLE—ABSTRACT P15 Strain % Gastric emptying Geometric center Lean 90.9 ± 1.7 8.35 ± 0.28 Obese 97.1 ± 0.6 ∗ 7.33 ± 0.30 ∗ ∗ P < 0.02 versus Lean.