132-OR: Peripheral Serotonin Regulates Dietary Fat Absorption and Intestinal Chylomicron Production

Abstract

Introduction: Diabetic dyslipidemia is a key feature of insulin resistance and is characterized by overproduction of chylomicron particles by the intestine. Chylomicron output can be regulated by hormones secreted from the intestine. Enterochromaffin cells are specialized enteroendocrine cells that secrete serotonin (5-HT). Gut-derived 5-HT is emerging as a regulator of systemic energy homeostasis by regulating adipose and liver lipid metabolism. Currently, the role of 5-HT on intestinal fat absorption and chylomicron production remains unknown. We hypothesize that 5-HT regulates postprandial intestinal fat absorption and chylomicron production. Methods/Results: Syrian golden hamsters underwent jugular cannulation surgery. The next day, hamsters received an oral fat load (200μl olive oil) followed by intravenous infusion of Triton WR-1339 to prevent lipoprotein clearance. Blood samples were collected prior to and up to 6 hours post fat load. Triglyceride-rich lipoproteins (TRL) which includes chylomicrons were isolated from plasma by density gradient ultracentrifugation and triglyceride (TG) content in this fraction was measured using an enzyme based colorimetric assay. Intravenous administration of 5-HT (1mg/kg) 5 minutes prior to oral fat load increased the rate of plasma TG and TRL-TG accumulation while higher doses of 5-HT (5 and 10mg/kg) produced a transient decrease in plasma TG and TRL-TG accumulation. Treatment with 5-HT4 receptor agonist, Bimu-8 (1mg/kg), increased plasma TG and TRL-TG accumulation. Endogenous 5-HT depletion by para-chloro-phenylalanine (PCPA), an inhibitor of 5-HT synthesis, reduced the rate of TG and TRL-TG accumulation compared to vehicle controls. Furthermore, enhancing 5-HT action by inhibiting 5-HT reuptake with fluoxetine increased the rate of TG and TRL-TG accumulation. Our results demonstrate that 5-HT is a key regulator of postprandial lipoprotein metabolism and could have important implications for diabetic dyslipidemia. Disclosure F. Raka: None. K. Adeli: None. Funding Canadian Institutes of Health Research (967131)