Effect of a high fat diet on lipid absorption and fatty acid transport in a rat model of short bowel syndrome

Abstract

Long chain fatty acids (LCFAs) appear to be powerful stimulants for small bowel adaptation in patients with short bowel syndrome (SBS). However, the dietary lipid content may alter intestinal lipid transport. The aim of this study was to investigate the effects of a high fat diet (HFD) on in vivo lipid absorption and molecular and cellular mechanisms of LCFAs uptake by the remaining bowel. Male Sprague-Dawley rats (240–280) were randomly assigned to one of three groups: sham rats fed normal chow (sham-NC), SBS rats fed NC (SBS-NC) and SBS rats fed HFD (SBS-HFD). SBS rats underwent a 75% small bowel resection. Rats were sacrificed on day 3 or 14. Body weight, fat intake and fat clearance (total fecal fat) were measured twice a week. Fat absorbability was calculated as intake minus clearance and was expressed as percent of intake. Total RNA from the mucosa of duodenum, jejunum and ileum was extracted using TRIZOL Reagent. Northern blot analysis was performed to determine FAT/CD36 mRNA levels. Enterocyte LCFA transport was measured on day 14. LCFA uptake was determined by measuring cellular [3H]-oleate uptake over time (4–120 s). Mean (±SE) FAT/CD36 mRNA levels and oleate uptake kinetic parameters were analyzed using ANOVA. Fat absorbability diminished after bowel resection, suggesting fat malabsorption. Remaining bowel in SBS-NC rats responded by an increase in FAT/CD36 mRNA levels in the duodenum and ileum on day 3, and the duodenum and jejunum on day 14 compared to sham-NC animals, and was accompanied by an increase in enterocyte LCFA transport in all segments. Exposure to a HFD for 14 days resulted in significantly increased fat absorbability after 3 days compared to SBS-NC rats. However, FAT/CD36 mRNA levels (vs. SBS-NC) decreased in all segments on day 3. On day 14, FAT/CD36 mRNA levels were decreased in the duodenum and ileum and were accompanied by reduced oleate uptake by isolated enterocytes in the ileum (vs. SBS-NC). In a rat model of SBS, early high fat diet increased lipid absorptive capacity of the intestinal remnant as seen by increased fat absorbability. The main mechanisms of this effect may be an acceleration of structural intestinal adaptation resulting in an increased number of enterocytes. However, at molecular and cellular levels HFD decreased mucosal FAT/CD36 mRNA levels and oleic acid uptake by isolated enterocytes.