Vasoactive intestinal peptide is a local mediator in a gut‐brain neural axis activating intestinal gluconeogenesis

Abstract

Intestinal gluconeogenesis (IGN) promotes metabolic benefits through activation of a gut-brain neural axis. However, the local mediator activating gluconeogenic genes in the enterocytes remains unknown. We show that (i) vasoactive intestinal peptide (VIP) signaling through VPAC1 receptor activates the intestinal glucose-6-phosphatase gene in vivo, (ii) the activation of IGN by propionate is counteracted by VPAC1 antagonism, and (iii) VIP-positive intrinsic neurons in the submucosal plexus are increased under the action of propionate. These data support the role of VIP as a local neuromodulator released by intrinsic enteric neurons and responsible for the induction of IGN through a VPAC1 receptor-dependent mechanism in enterocytes.

Impact of Glycosidic Bond Configuration on Short Chain Fatty Acid Production from Model Fermentable Carbohydrates by the Human Gut Microbiota

“…There is increasing evidence that bioactive molecules produced during colonic bacterial fermentation play a central role in the beneficial effects of non-digestible carbohydrates (NDC) [ 1 ]. Dietary NDC are the major fermentable component of dietary fiber and have been associated with positive health outcomes related to appetite regulation, body composition and metabolic health [ 2 , 3 ]. Short chain fatty acids (SCFA) are the main products of saccharolytic bacterial fermentation of NDC, with acetate, propionate, and butyrate being the principal SCFA produced [ 4 ].…”

“…Acetate is a central metabolite in intermediary metabolism and is involved in lipid and cholesterol synthesis [ 6 , 7 ] and central appetite regulation [ 8 ]. In addition to inhibiting de novo cholesterol and lipid synthesis [ 9 , 10 ], propionate is a precursor for intestinal [ 3 ] and hepatic gluconeogenesis [ 7 ]. Selectively increasing colonic propionate in humans, through the consumption of inulin propionate ester, has been shown to regulate appetite, reduce hepatic and intra-abdominal visceral fat depots and reduce body weight gain in overweight adults [ 2 ].…”

Impact of Intestinal Peptides on the Enteric Nervous System: Novel Approaches to Control Glucose Metabolism and Food Intake

“…Thus, because VIP is expressed in neurons present in submucosal and myenteric plexuses, and is modulated by the microbiota derived compounds produced by the fermentation. These findings also suggest that it exist a local release of VIP by enteric neurons which may be a key mechanism by which nutrients, peptides, and microbial metabolites are finally involved in the activation of IGN and thus control food intake and glucose metabolism ( 77 ).…”

Microbiota, as a New Target of Pathogenetic Treatment of Type 2 Diabetes Mellitus

“…Сьогодні вважають, що інтестинальний глюконеогенез має безпосередній вплив на активацію осі «кишечник-головний мозок», хоча безпосереднього медіатора активності генів глюконеогенезу ще не знайдено [18]. Натомість з'ясовано, що ВІП через рецептор VPAC1 індукує кишковий ген глюкозо-6-фосфатази in vivo.…”