We previously demonstrated increased villus height following genetic deletion, or knockout, of retinoblastoma protein (Rb in the intestinal epithelium (Rb-IKO. Here we determined the functional consequences of augmented mucosal growth on intestinal fat absorption and following a 50% small bowel resection (SBR. Mice with constitutively disrupted Rb expression in the intestinal epithelium (Rb-IKO along with their floxed (wild-type, WT littermates were placed on a high-fat diet (HFD, 42% kcal fat for 54 wk. Mice were weighed weekly, and fat absorption, indirect calorimetry, and MRI body composition were measured. Rb-IKO mice were also subjected to a 50% SBR, followed by HFD feeding for 33 wk. In separate experiments, we examined intestinal fat absorption in mice with conditional (tamoxifen-inducible intestinal Rb (inducible Rb-IKO deletion. Microarray revealed that the transcriptional expression of lipid absorption/transport genes was significantly reduced in constitutive Rb-IKO mice. These mice demonstrated greater mucosal surface area yet manifested paradoxically impaired intestinal long-chain triglyceride absorption and decreased cholesterol absorption. Despite attenuated lipid absorption, there were no differences in metabolic rate, body composition, and weight gain in Rb-IKO and WT mice at baseline and following SBR. We also confirmed fat malabsorption in inducible Rb-IKO mice. We concluded that, despite an expanded mucosal surface area, Rb-IKO mice demonstrate impaired lipid absorption without compensatory alterations in energy homeostasis or body composition. These findings underscore the importance of delineating structural/functional relationships in the gut and suggest a previously unknown role for Rb in the regulation of intestinal lipid absorption.
|Journal||American Journal of Physiology - Gastrointestinal and Liver Physiology|
|State||Published - May 15 2014|
- Fat metabolism
- Retinoblastoma protein