title: Protein-induced satiety is abolished in the absence of intestinal gluconeogenesis.
abstract: Protein-enriched diets are well known to initiate satiety effects in animals and humans. It has been recently suggested that this might be dependent on the induction of gluconeogenesis in the intestine. The resulting intestinal glucose release, detected by a "so-called" glucose sensor located within the walls of the portal vein and connected to peripheral afferents, activates hypothalamic nuclei involved in the regulation of food intake, in turn initiating a decrease in hunger. To definitively demonstrate the role of intestinal gluconeogenesis in this mechanism, we tested the food intake response to a protein-enriched diet in mice with an intestine-specific deletion (using an inducible Cre/loxP strategy) of the glucose-6 phosphatase gene (I-G6pc(-/-) mice) encoding the mandatory enzyme for glucose production. There was no effect on food intake in I-G6pc(-/-) mice fed on a standard rodent diet compared to their wild-type counterparts. After switching to a protein-enriched diet, the food intake of wild-type mice decreased significantly (by about 20% of daily calorie intake), subsequently leading to a decrease of 12 ± 2% of initial body weight after 8 days. On the contrary, I-G6pc(-/-) mice were insensitive to the satiety effect induced by a protein-enriched diet and preserved their body weight. These results provide molecular evidence of the causal role of intestinal gluconeogenesis in the satiety phenomenon initiated by protein-enriched diets.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U855, Lyon, F-69008, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Penhoat
authors.forename: Elodie
authors.initials: E
authors.lastname: Mutel
authors.forename: Marta
authors.initials: M
authors.lastname: Amigo-Correig
authors.forename: Bruno
authors.initials: B
authors.lastname: Pillot
authors.forename: Anne
authors.initials: A
authors.lastname: Stefanutti
authors.forename: Fabienne
authors.initials: F
authors.lastname: Rajas
authors.forename: Gilles
authors.initials: G
authors.lastname: Mithieux
mesh_terms: D000818:Animals; D004044:Dietary Proteins / Q000378:metabolism*; D004435:Eating / Q000502:physiology*; D005943:Gluconeogenesis / Q000502:physiology*; D005952:Glucose-6-Phosphatase / Q000235:genetics* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D012527:Satiation / Q000502:physiology*
chemical_list: D004044:Dietary Proteins; D005952:Glucose-6-Phosphatase