title: A high-fat diet regulates gastrin and acid secretion through primary cilia.
abstract: The role of primary cilia in the gastrointestinal tract has not been examined. Here we report the presence of primary cilia on gastric endocrine cells producing gastrin, ghrelin, and somatostatin (Sst), hormones regulated by food intake. During eating, cilia in the gastric antrum decreased, whereas gastric acid and circulating gastrin increased. Mice fed high-fat chow showed a delayed decrease in antral cilia, increased plasma gastrin, and gastric acidity. Mice fed high-fat chow for 3 wk showed lower cilia numbers and acid but higher gastrin levels than mice fed a standard diet, suggesting that fat affects gastric physiology. Ex vivo experiments showed that cilia in the corpus responded to acid and distension, whereas cilia in the antrum responded to food. To analyze the role of gastric cilia, we conditionally deleted the intraflagellar transport protein Ift88 (Ift88(-/fl)). In fed Ift88(-/fl) mice, gastrin levels were higher, and gastric acidity was lower. Moreover, gastrin and Sst gene expression did not change in response to food as in controls. At 8 mo, Ift88(-/fl) mice developed foveolar hyperplasia, hypergastrinemia, and hypochlorhydria associated with endocrine dysfunction. Our results show that components of food (fat) are sensed by antral cilia on endocrine cells, which modulates gastrin secretion and gastric acidity.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Milena
authors.initials: M
authors.lastname: Saqui-Salces
authors.forename: William E
authors.initials: WE
authors.lastname: Dowdle
authors.forename: Jeremy F
authors.initials: JF
authors.lastname: Reiter
authors.forename: Juanita L
authors.initials: JL
authors.lastname: Merchant
mesh_terms: D000818:Animals; D002923:Cilia / Q000502:physiology*; D059305:Diet, High-Fat; D005260:Female; D005502:Food; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D005755:Gastrins / Q000502:physiology*; D054439:Ghrelin / Q000096:biosynthesis; D006965:Hyperplasia / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011706:Pyloric Antrum; D013270:Stomach / Q000473:pathology / Q000648:ultrastructure; D025521:Tumor Suppressor Proteins / Q000172:deficiency
chemical_list: D005755:Gastrins; D054439:Ghrelin; C490898:Tg737Rpw protein, mouse; D025521:Tumor Suppressor Proteins