Secretory and absorptive dysfunctions in ob/ob mouse jejunum are sex‐dependent (1117.1)

Abstract

Sex‐dependent differences in intestinal absorption and intestinal secretion in the ob/ob leptin‐deficient obese mouse are poorly understood. We used male and female ob/ob and lean mice aged ~14 weeks. The goal of this study was to characterize jejunal function in this clinically relevant mouse model. We measured transepithelial short circuit current (Isc), a measure of chloride secretion, across freshly isolated segments of jejunum from ob/ob and lean mice. Compared to lean controls, basal Isc was significantly decreased by 24 µA/cm2 (P<0.05, n=9) in ob/ob females and significantly decreased by 30 µA/cm2 (P<0.05, n=10‐11) in ob/ob males. Reduced basal Isc in ob/ob males is partly attributed to a significant 2‐fold decrease in CFTR expression. The contribution of key transporters involved in promoting chloride secretion are currently under evaluation. While crypt depth was unchanged in ob/ob males, the number of goblet cells/crypt was 2‐fold greater and this may also account for, in part, the reduced basal Isc in ob/ob males. Villi length and total small intestinal length were both significantly increased in ob/ob female and male mice, suggesting a greater surface area for absorptive function. These structural changes likely contribute towards the obese phenotype. Expression of the fructose transporter protein, GLUT5 (normalized to GAPDH), was significantly increased 1.9‐fold (P<0.05, n=12‐15) in male ob/ob mice compared to leans, which likely contributes to the diabetic/obese phenotype of ob/ob males. Expression of the glucose co‐transporter protein, SGLT1 (normalized to GAPDH), was significantly decreased 30% (P<0.05, n=8‐9) in female ob/ob mice compared to leans. These data suggest that basal jejunal Isc in ob/ob mice is deficient, and may contribute towards slower transit times in the gastrointestinal tract in the ob/ob mice. Interestingly, while both female and male ob/ob mice are obese, the specific secretory and absorptive dysfunctions are not comparable in both sexes.Grant Funding Source: Supported by NIH R15 DK071625‐01A2