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.

Adenylate Cyclase Type III Is Not a Ubiquitous Marker for All Primary Cilia during Development

“…In the present study, we did not identify a primary cilium using either acetylated-tubulin or AC3-directed antibodies during development of these epithelia in mouse and human gut neither at the apical membrane of differentiated enterocytes or goblet cells, nor in cells of the stem cells region during development. We did not observe cilia in the gastric epithelium as did Saqui-Salces et al [31] in gastric endocrine cells in adult mice; however, it is known that endocrine cells appear after 14W in human [32] and in late fetal period in rodents [33]. …”

“…Many differentiated cells of single layered epithelia have a primary cilium except in the small intestine and colon where enterocytes and goblet cells lack an apical cilium, as demonstrated in the adult mouse [31]. In the present study, we did not identify a primary cilium using either acetylated-tubulin or AC3-directed antibodies during development of these epithelia in mouse and human gut neither at the apical membrane of differentiated enterocytes or goblet cells, nor in cells of the stem cells region during development.…”

A Chronological Increase in Gastric Acid Secretion from 1995 to 2014 in Young Japanese Healthy Volunteers under the Age of 40 Years Old

“…For example, a very recent nationwide survey conducted in 2013 indicated that 47% of Japanese men with an age of 20-29 have a modern westernized dietary pattern consisting of meat, non-Japanese noodles, and sugar sweetened beverages, whereas only 2.9% of those with an age of 60-69 had such a dietary pattern; instead, men aged 60-69 have a more traditional Japanese dietary pattern consisting of rice and vegetables (Katagiri et al 2015). Because dietary fat intake is known to stimulate gastric acid secretion (Saqui-Salces et al 2012), such differences in dietary pattern among Japanese generations could be at least partly responsible for the different chronological changes in gastric acid secretion between young and elderly Japanese people.…”

The importance of the gastrorenal axis in the control of body sodium homeostasis

“…The normal fasting plasma gastrin levels range from 100 to 200 pg/ml; the meal-stimulated blood gastrin concentration is about 2–4.5-fold higher, equivalent to a concentration of about 400 pM (Li et al, 2014 Saqui-Salces et al, 2012). Among the radiolabeled analogues of several enterokines (CCK, gastrin, bombesin, neurotensin, and somatostatin), gastrin is taken up and retained to the greatest extent by renal proximal tubules (100–1000-fold), presumably by reabsorption from the glomerular filtrate (Melis et al, 2005, Melicharova et al, 2014).…”