Role of the clock gene Bmal1 and the gastric ghrelin-secreting cell in the circadian regulation of the ghrelin-GOAT system
| Autor: | Laurien Vancleef, Inge Depoortere, Jorien Laermans, Jan Tack |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Circadian clock Gene Expression Endogeny Biology Article Eating Mice Cell Line Tumor Circadian Clocks Orexigenic Internal medicine Gene expression medicine Animals Secretion RNA Messenger Circadian rhythm Mice Knockout Multidisciplinary Stomach digestive oral and skin physiology ARNTL Transcription Factors Membrane Proteins Ghrelin Circadian Rhythm CLOCK Endocrinology Gastric Mucosa Female Cues Acyltransferases Gene Deletion hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep16748 |
| Popis: | As adequate food intake is crucial to survival, organisms have evolved endogenous circadian clocks to generate optimal temporal patterns of food-related behavior and physiology. The gastric ghrelin-secreting cell is thought to be part of this network of peripheral food-entrainable oscillators (FEOs), regulating the circadian release of this orexigenic peptide. This study aimed to determine the role of the core clock gene Bmal1 and the gastric ghrelin-secreting cell as an FEO in the circadian rhythmicity of ghrelin expression and secretion in vivo and in vitro. Bmal1-deficient mice not only lacked circadian rhythmicity in plasma ghrelin levels and food intake, but also showed decreased gastric mRNA expression of ghrelin and ghrelin O-acyltransferase (GOAT), the ghrelin activating enzyme. Furthermore, in the absence of the hypothalamic master clock, food-related stimuli entrained the molecular clock of gastric ghrelinoma cells to regulate the rhythmic release of ghrelin. Divergent responses in octanoyl and total ghrelin release towards different food cues were observed, suggesting that the FEO also regulates the circadian rhythmicity of GOAT. Collectively, these findings indicate that circadian rhythmicity of ghrelin signaling requires Bmal1 and is driven by a food-responsive clock in the gastric ghrelin-secreting cell that not only regulates ghrelin, but also GOAT activity. |
| Databáze: | OpenAIRE |
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