Lipid-rich diet enhances L-cell density in obese subjects and in mice through improved L-cell differentiation. (20th May 2015)

• Record Type: Journal Article
• Authors: Aranias, Thomas; Grosfeld, Alexandra; Poitou, Christine; Omar, Amal Ait; Le Gall, Maude; Miquel, Sylvie; Garbin, Kévin; Ribeiro, Agnès; Bouillot, Jean-Luc; Bado, André; Brot-Laroche, Edith; Clément, Karine; Leturque, Armelle; Guilmeau, Sandra; Serradas, Patricia
• Is Part Of: Journal of nutritional science. Volume 4(2015)
• Page Start: 3
• Page End: 12
• Publication Date: 2015-05-20
• Subjects: Nutrition -- Periodicals; 612.305
• DOI: 10.1017/jns.2015.11
• Languages: English
• ISSNs: 2048-6790

Abstract

<abstract abstract-type="normal"> <title>Abstract</title> <p>The enterohormone glucagon-like peptide-1 (GLP-1) is required to amplify glucose-induced insulin secretion that facilitates peripheral glucose utilisation. Alteration in GLP-1 secretion during obesity has been reported but is still controversial. Due to the high adaptability of intestinal cells to environmental changes, we hypothesised that the density of GLP-1-producing cells could be modified by nutritional factors to prevent the deterioration of metabolic condition in obesity. We quantified L-cell density in jejunum samples collected during Roux-en-Y gastric bypass in forty-nine severely obese subjects analysed according to their fat consumption. In mice, we deciphered the mechanisms by which a high-fat diet (HFD) makes an impact on enteroendocrine cell density and function. L-cell density in the jejunum was higher in obese subjects consuming >30 % fat compared with low fat eaters. Mice fed a HFD for 8 weeks displayed an increase in GLP-1-positive cells in the jejunum and colon accordingly to GLP-1 secretion. The regulation by the HFD appears specific to GLP-1-producing cells, as the number of PYY (peptide YY)-positive cells remained unchanged. Moreover, genetically obese <italic>ob/ob</italic> mice did not show alteration of GLP-1-positive cell density in the jejunum or colon, suggesting that obesity <italic>per se</italic> is not sufficient to trigger the mechanism. The higher L-cell density in HFD-fed mice involved a rise in L-cell terminal differentiation as witnessed by the increased expression of transcription factors downstream of neurogenin3 (<italic>Ngn3</italic>). We suggest that the observed increase in GLP-1-positive cell density triggered by high fat consumption in humans and mice might favour insulin secretion and therefore constitute an adaptive response of the intestine to balance diet-induced insulin resistance.</p> </abstract>