Abstract 445: Niacin Beneficially Alters the Secretion of Intestinal-derived TRL and HDL in a Rat Model of Insulin Resistance

Abstract

Introduction The intestine secretes discrete fractions of triglyceride (TG) rich apoB-chylomicrons (CM) and HDL particles into mesenteric lymph. Insulin resistance (IR) is associated with overproduction of intestinal CM however, the effect of IR on intestinal HDL secretion remains unknown. Niacin has been shown to reduce plasma TG while increasing HDL-C, however it is unknown if niacin modulates intestinal lymphatic CM and HDL secretion. Objective To determine the effect of niacin on the secretion and composition of intestinal lymphatic CM and HDL in a model of IR (JCR:LA- cp rat). Methods IR rats were fed control chow or chow supplemented with niacin (0.5% or 1% w/w) for 6 weeks. The mesenteric lymph duct was cannulated and lymph sampled following an intra-gastric intralipid ( fed ) infusion for 6hrs. The lymphatic CM (<1.006g/ml) and HDL (1.063-1.21g/ml) fractions were separated by density ultracentrifugation. Results IR rats over-secreted (2-fold) lymph apoB-CMs, while simultaneously reducing lymphatic apoA1-HDL (-47%) secretion compared to non-IR rats. In addition, CM and HDL particles from IR rats were found to be enriched in TG (64 and 86% respectively). Interestingly, niacin stimulated the secretion of lymph HDL (>60%), as well as attenuated lymph CM (-53%) secretion compared to control. Niacin treatment was also found to normalize the TG content of both lymph-CM and lymph-HDL particles. Conclusion IR appears to stimulate the intestine to over-secrete apoB-CM as well as reduce apoAI-HDL secretion into lymph, potentially contributing to particle dysfunction. Niacin may contribute to improving CVD risk by reducing the over-secretion of intestinal pro-atherogenic apoB-particles, whilst restoring the number and TG enrichment of intestinal anti-atherogenic apoAI-particles.