title: The role of nutrient sensing in the metabolic changes after gastric bypass surgery.
abstract: Taste receptors coupled to the gustatory G-protein, gustducin, on enteroendocrine cells sense nutrients to regulate gut hormone release. During Roux-en-Y gastric bypass (RYGB) surgery, the altered nutrient flow to more distal regions can affect gustducin-mediated gut hormone release and hence energy and glucose homeostasis. We studied the role of gustducin-mediated signaling in the metabolic improvements and intestinal adaptations along the gut after RYGB surgery in wild-type (WT) and α-gustducin-/-(α-gust-/-) mice. RYGB surgery decreased body weight in WT and α-gust-/-mice, whereas food intake was only decreased in WT mice. Pair-feeding to the RYGB group improved glucose homeostasis to a similar extent in WT mice. GLP1 levels were increased in both genotypes, PYY levels in α-gust-/-mice and octanoyl ghrelin levels were not affected after RYGB surgery. In WT mice, nutrients act via α-gustducin to increase L-cell differentiation (foregut) and L-cell number (foregut and hindgut) in a region-dependent manner. In α-gust-/-mice, the effect on gut hormone levels is probably tuned via increased peptide sensor and glucose transporter expression in the Roux limb and increased caecal butyrate and propionate levels in the hindgut that activate free fatty acid receptors. Finally, signaling via α-gustducin plays a role in the increased ion transport of the foregut but not in the improvement in colonic barrier function. In conclusion, RYGB surgery decreased body weight in both WT and α-gust-/-mice. Elevated plasma GLP1 and PYY levels might mediate this effect, although α-gustducin differentially affects several regulatory systems in the foregut and hindgut, tuning gut hormone release.
authors.affiliation: TARGIDKU Leuven, Leuven, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Steensels
authors.affiliation: Abdominal SurgeryUniversity Hospital of Leuven, Leuven, Belgium.
authors.forename: Matthias
authors.initials: M
authors.lastname: Lannoo
authors.affiliation: TARGIDKU Leuven, Leuven, Belgium.
authors.forename: Bert
authors.initials: B
authors.lastname: Avau
authors.affiliation: TARGIDKU Leuven, Leuven, Belgium.
authors.forename: Jorien
authors.initials: J
authors.lastname: Laermans
authors.affiliation: TARGIDKU Leuven, Leuven, Belgium.
authors.forename: Laurien
authors.initials: L
authors.lastname: Vancleef
authors.affiliation: TARGIDKU Leuven, Leuven, Belgium.
authors.forename: Ricard
authors.initials: R
authors.lastname: Farré
authors.affiliation: TARGIDKU Leuven, Leuven, Belgium.
authors.forename: Kristin
authors.initials: K
authors.lastname: Verbeke
authors.affiliation: TARGIDKU Leuven, Leuven, Belgium inge.depoortere@kuleuven.be.
authors.forename: Inge
authors.initials: I
authors.lastname: Depoortere
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000502:physiology; D002452:Cell Count; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D019858:Enteroendocrine Cells / Q000378:metabolism; D015390:Gastric Bypass; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000502:physiology; D015293:Transducin / Q000235:genetics* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; C075192:gustducin; D052216:Glucagon-Like Peptide 1; D015293:Transducin
keywords: bariatric surgery; gut hormones; nutrient sensing; obesity; permeability