Diabetic dyslipidemia is characterized by overproduction of ApoB48-containing chylomicron particles, which are an independent risk factor for the development of cardiovascular disease. Chylomicron production is regulated in-part by gut-derived hormones such as glucagon-like peptide (GLP)-1. Notably, we have shown that GLP-1 acts in a neuroendocrine manner; activating GLP-1 receptor (GLP-1R) containing vagal neurons in the portal vein thereby reducing postprandial lipemia. GLP-1Rs have also been identified in the vagal nodose ganglion (NG), however their relevance to lipoprotein metabolism is yet unknown.

Syrian Golden hamsters received bilateral NG injections of either PBS vehicle, the GLP-1R agonist exendin-4, the GLP-1R antagonist exendin 9-39, or a combination of both. To investigate the propagation of vagal signalling from the portal bed hamsters received injections of GLP-1 or PBS vehicle into the portal vein, and concurrent NG injections of either exendin-4 or exendin 9-39. In addition, selective deafferination of GLP-1R-containing NG neurons was achieved via nodose injection of the cytotoxin saponin conjugated to exendin-4. After treatment, all animals received a gavage of olive oil, and an intravenous infusion of tyloxapol to prevent lipoprotein clearance. Postprandial accumulation of TG-rich lipoproteins was assessed via blood draws over a 6-hour period. Triglyceride-rich lipoprotein (TRL) fractions were then isolated via density ultracentrifugation for biochemical analysis.

NG injection of exendin-4 significantly reduced postprandial plasma TG and TRL. The ability of portal GLP-1 to reduce postprandial lipemia was lost with 9-39 injection into the NG, suggesting that active GLP-1R in this ganglion are requisite to elicit this effect. Finally, selective deafferination of NG GLP-1R containing neurons caused significant rises in postprandial TG and TRL, underscoring the importance of vagal signalling in intestinal lipoprotein regulation.


S.S. Hoffman: None. K. Adeli: None.


Canadian Institutes of Health Research (967131)

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