GLP-1 reduces intestinal lymph flow, triglyceride absorption, and apolipoprotein production in rats

Abstract

Glucagon-like peptide 1 (GLP-1) is a gastrointestinal hormone secreted in response to meal ingestion by enteroendocrine L cells located predominantly in the lower small intestine and large intestine. GLP-1 inhibits the secretion and motility of the upper gut and has been suggested to play a role in the "ileal brake." In this study, we investigated the effect of recombinant GLP-1-(7-36) amide (rGLP-1) on lipid absorption in the small intestine in intestinal lymph duct-cannulated rats. In addition, the effects of rGLP-1 on intestinal production of apolipoprotein (apo) B and apo A-IV, two apolipoproteins closely related to lipid absorption, were evaluated. rGLP-1 was infused through the jugular vein, and lipids were infused simultaneously through a duodenal cannula. Our results showed that infusion of rGLP-1 at 20 pmol.kg(-1).min(-1) caused a dramatic and prompt decrease in lymph flow from 2.22 +/- 0.15 (SE) ml/h at baseline (n = 6) to 1.24 +/- 0.06 ml/h at 2 h (P < 0.001). In contrast, a significant increase in lymph flow was observed in the saline (control) group: 2.19 +/- 0.20 and 3.48 +/- 0.09 ml/h at baseline and at 6 h of lipid infusion, respectively (P < 0.001). rGLP-1 also inhibited intestinal triolein absorption (P < 0.05) and lymphatic apo B and apo A-IV output (P < 0.05) but did not affect cholesterol absorption. In conclusion, rGLP-1 dramatically decreases intestinal lymph flow and reduces triglyceride absorption and apo B and apo A-IV production. These findings suggest a novel role for GLP-1 in lipid absorption.

Glucagon-like peptide 1 abolishes the postprandial rise in triglyceride concentrations and lowers levels of non-esterified fatty acids in humans

“…Alternatively, it seems possible that GLP-1 directly inhibited triglyceride absorption from the gut, potentially through inhibition of gastric lipases [21]. This explanation would be consistent with a recent series of elegant experiments in rats demonstrating that GLP-1 reduces the intestinal absorption of triolein and inhibits intestinal lymph flow [22]. It therefore appears possible that a combination of delayed gastric emptying and reduced intestinal lipid absorption prevented the postprandial increase in triglyceride levels.…”

The glucagon-like peptide 1 receptor is essential for postprandial lipoprotein synthesis and secretion in hamsters and mice

“…A DPP-4 inhibitor attenuates dyslipidaemia in fructose-fed hamsters As increased incretin action can attenuate postprandial plasma lipid accumulation [18,19,26], we examined the consequences of DPP-4 inhibition for accumulation of triacylglycerol and cholesterol in hamsters fed a high-fructose diet (60%), which promotes dyslipidaemia and mild insulin resistance [23]. A high-fructose diet for 10 days prior to start of sitagliptin treatment produced a significant increase in plasma triacylglycerol and cholesterol (p=0.0002 and p=0.006, respectively) (Fig.…”

“…DPP-4 inhibition lowers fasting and postprandial glycaemia in patients with type 2 diabetes mellitus [13,14]; hence there is considerable interest in understanding the effects of incretins and DPP-4 inhibitors on plasma lipid profiles [15]. Acute administration of GIP reduces circulating chylomicrons, probably by promoting triacylglycerol catabolism by adipose tissue [16,17]; GLP-1 also attenuates postprandial triacylglycerol secretion [18,19], although the exact underlying mechanisms are not clear.…”

Vildagliptin therapy reduces postprandial intestinal triglyceride-rich lipoprotein particles in patients with type 2 diabetes

“…The recent demonstration that GLP-1 reduces intestinal TG absorption and apo B and apo A-IV production in rats [3] provides one potential mechanism that could be addressed in future studies. A modest decrease in TG absorption could also explain the lack of weight gain during the study, whereas there was a clear improvement in glycaemic controls.…”

“…Although clinical studies to date indicate that fasting lipid levels are minimally affected by vildagliptin treatment, animal studies suggest that glucagon-like peptide-1 (GLP-1) reduces intestinal triglyceride (TG) absorption and apolipoprotein (apo) production [3] and that glucose-dependent insulinotropic peptide (GIP) increases chylomicron clearance [4] and reduces post-load TG levels [5]. Because vildagliptin increases plasma levels of the active forms of both GLP-1 and GIP in diabetic patients [1], the present study was performed to assess the effects of vildagliptin on postprandial lipaemia.…”