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Suppression of enteroendocrine cell glucagon-like peptide (GLP)-1 release by fat-induced small intestinal ketogenesis: a mechanism targeted by Roux-en-Y gastric bypass surgery but not by preoperative very-low-calorie diet
- Source :
- Gut, Gut, BMJ Publishing Group, 2019, 69, pp.1423-1431. ⟨10.1136/gutjnl-2019-319372⟩
- Publication Year :
- 2019
- Publisher :
- HAL CCSD, 2019.
-
Abstract
- ObjectiveFood intake normally stimulates release of satiety and insulin-stimulating intestinal hormones, such as glucagon-like peptide (GLP)-1. This response is blunted in obese insulin resistant subjects, but is rapidly restored following Roux-en-Y gastric bypass (RYGB) surgery. We hypothesised this to be a result of the metabolic changes taking place in the small intestinal mucosa following the anatomical rearrangement after RYGB surgery, and aimed at identifying such mechanisms.DesignJejunal mucosa biopsies from patients undergoing RYGB surgery were retrieved before and after very-low calorie diet, at time of surgery and 6 months postoperatively. Samples were analysed by global protein expression analysis and Western blotting. Biological functionality of these findings was explored in mice and enteroendocrine cells (EECs) primary mouse jejunal cell cultures.ResultsThe most prominent change found after RYGB was decreased jejunal expression of the rate-limiting ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHMGCS), corroborated by decreased ketone body levels. In mice, prolonged high-fat feeding induced the expression of mHMGCS and functional ketogenesis in jejunum. The effect of ketone bodies on gut peptide secretion in EECs showed a ∼40% inhibition of GLP-1 release compared with baseline.ConclusionIntestinal ketogenesis is induced by high-fat diet and inhibited by RYGB surgery. In cell culture, ketone bodies inhibited GLP-1 release from EECs. Thus, we suggest that this may be a mechanism by which RYGB can remove the inhibitory effect of ketone bodies on EECs, thereby restituting the responsiveness of EECs resulting in increased meal-stimulated levels of GLP-1 after surgery.
- Subjects :
- 0301 basic medicine
Hydroxymethylglutaryl-CoA Synthase
Male
Enteroendocrine cell
Ketone Bodies
medicine.disease_cause
Small Bowel
Jejunum
Mice
0302 clinical medicine
Glucagon-Like Peptide 1
Ketogenesis
Postoperative Period
Intestinal Mucosa
Cells, Cultured
Phospholipids
2. Zero hunger
3-Hydroxybutyric Acid
Gastroenterology
Peptide secretion
Ketones
Middle Aged
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
3. Good health
Very low calorie diet
medicine.anatomical_structure
Liver
Preoperative Period
diabetes mellitus
Ketone bodies
Emulsions
Female
enterocyte biology
medicine.medical_specialty
Fat Emulsions, Intravenous
food.diet
Enteroendocrine Cells
Primary Cell Culture
Gastric Bypass
030209 endocrinology & metabolism
Glucagon
03 medical and health sciences
food
Internal medicine
medicine
Animals
Humans
Caloric Restriction
Gastric bypass surgery
business.industry
nutritional and metabolic diseases
Anastomosis, Roux-en-Y
glucagen-like peptides
Dietary Fats
Soybean Oil
obesity surgery
Mice, Inbred C57BL
030104 developmental biology
Endocrinology
business
Subjects
Details
- Language :
- English
- ISSN :
- 00175749
- Database :
- OpenAIRE
- Journal :
- Gut, Gut, BMJ Publishing Group, 2019, 69, pp.1423-1431. ⟨10.1136/gutjnl-2019-319372⟩
- Accession number :
- edsair.doi.dedup.....f66faba1d55026dcf7a10d07a91067ed