Novel Role of Enteral Monosaccharides in Intestinal Lipoprotein Production in Healthy Humans

Abstract

Objective-Overproduction of triglyceride-rich lipoproteins (TRLs) by liver and intestine contributes to hypertriglyceridemia and may increase cardiovascular risk. Dietary carbohydrates, especially fructose, have been shown to amplify postprandial lipemia but little is known about its effect on intestinal TRL particle production. Here, we examined intestinal and hepatic TRL particle production in response to enteral glucose or fructose in the presence of enteral lipid. Approach and Results-In 2 randomized studies, 4 to 6 weeks apart, 7 healthy male subjects received intraduodenal infusion of Intralipid plus saline or glucose. TRL-apolipoprotein (apo) B48 and apoB100 kinetics were assessed under pancreatic clamp conditions. In a separate study of another 7 subjects under similar conditions, glucose was replaced by fructose. When coinfused with Intralipid into the duodenum, glucose markedly stimulated TRL-apoB48 production (P<0.01), with a concomitant moderate increase in fractional clearance (P<0.05), resulting in net elevation of TRLapoB48 concentration. TRL-apoB100 concentration, fractional clearance, and production were not significantly affected by glucose. When glucose was replaced by fructose, both TRL-apoB100 and apoB48 production (P<0.05), but not fractional clearance, were enhanced compared with Intralipid alone. Conclusions-These results reveal a novel role of monosaccharides in acutely enhancing intestinal lipoprotein particle production, thereby aggravating hyperlipidemia. of these monosaccharides on pancreatic hormone secretion, we elected to assess TRL kinetics under conditions of a pancreatic clamp, in which insulin, glucagon, and growth hormone secretion were suppressed by somatostatin, with concurrent replacement of these hormones at rates that mimic their basal rates of secretion. In addition, because intestinal infusion of lipids and monosaccharides affect gastric emptying to variable extents, 20,21 lipids and glucose or fructose were infused directly into the duodenum via a nasoduodenal tube (Figure 1). Materials and MethodsMaterials and Methods are available in the online-only Supplement. Results Lipid+Glucose Versus Lipid+Saline Study (n=7)Enteral Glucose Elevated Plasma and TRL-TG Plasma glucose, TG, free fatty acid (FFA), and TRL-TG were not different before intraduodenal infusion of either normal saline (NS) or glucose. As expected, coinfusion of glucose with Intralipid resulted in higher plasma glucose levels in GLU versus NS throughout the study period ( Figure IA in the online-only Data Supplement). TG levels in both plasma (GLU=0.91±0.08 versus NS=0.63±0.13 mg/L, P<0.05) and TRL (GLU=0.45±0.05 versus NS=0.30±0.07 mg/L, P<0.05) were higher in GLU versus NS during the 10-hour lipoprotein turnover period (Figure 2A and 2C). Plasma FFA were lower in GLU compared with NS ( Figure 2B), possibly attributable to relatively higher insulin levels in response to glucose infusion ( Figure IB in the online-only Data Supplement). Circulating levels of C-peptide were higher in GLU versus NS during th...

Intravenous Glucose Acutely Stimulates Intestinal Lipoprotein Secretion in Healthy Humans

“…The magnitude of enhanced apoB48 production by hyperglycemia (44% increase compared with saline control), the primary outcome, in this study was less than that seen previously with enteral glucose (≈6-fold). 17 One possible interpretation is that stimulation by glucose is stronger from the luminal side than from the basolateral side of the enterocyte. Figure 1.…”

“…16 In previous studies, we have demonstrated that coinfusion of monosaccharides (either glucose or fructose) with lipid emulsion directly into the duodenum promotes TRL particle production during 10-hour kinetic studies. 17 Although enteral sources of simple sugars may directly stimulate chylomicron particle production in intestinal enterocytes, they also elevated circulating levels of glucose. In this current experiment, we tested the hypothesis that intravenous glucose infusion, with its associated elevation in circulating glucose level, is capable of stimulating intestinal (and possibly) hepatic lipoprotein particle production in humans.…”

Recent advances in physiological lipoprotein metabolism

“…Postprandially the majority of the chylomicron triglycerides are sequestered by extrahepatic tissues (mainly adipose) following hydrolysis by the insulin-stimulated LPL [323]. Intestinally derived hormones glucagon-like peptide-1 and gastric inhibitory polypeptide enhance glucose stimulated insulin secretion by pancreatic β cells [324]. During fasting states growth hormone increases lipolysis and free fatty acid levels [325].…”

High-Dose Resveratrol Treatment for 2 Weeks Inhibits Intestinal and Hepatic Lipoprotein Production in Overweight/Obese Men

“…1,2 Recently, we have shown that, in healthy human volunteers, intestinal secretion of apoB-48-containing TRL particles is regulated by free fatty acids, 3 dietary monosaccharides (glucose and fructose), 4 and hormones such as insulin 5 and glucagon-like peptide-1. 6 Individuals with obesity/overweight, insulin resistance, 7 and type 2 diabetes mellitus 8 have increased production of apoB-48 TRL particles.…”