Intestinal HIF-2α Regulates GLP-1 Secretion via Lipid Sensing in L-Cells

Sun, 2018, The regulation of peripheral metabolism by gut-derived hormones, Front Endocrinol (Lausanne), 9, 754, 10.3389/fendo.2018.00754 Krieger, 2020, Intestinal glucagon-like peptide-1 effects on food intake: physiological relevance and emerging mechanisms, Peptides, 131, 170342, 10.1016/j.peptides.2020.170342 Shah, 2014, Effects of GLP-1 on appetite and weight, Rev Endocr Metab Disord, 15, 181, 10.1007/s11154-014-9289-5 Muller, 2019, Glucagon-like peptide 1 (GLP-1), Mol Metab, 30, 72, 10.1016/j.molmet.2019.09.010 Reimann, 2008, Glucose sensing in L cells: a primary cell study, Cell Metab, 8, 532, 10.1016/j.cmet.2008.11.002 Duca, 2021, The metabolic impact of small intestinal nutrient sensing, Nat Commun, 12, 903, 10.1038/s41467-021-21235-y Hirasawa, 2005, Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120, Nat Med, 11, 90, 10.1038/nm1168 Ghislain, 2021, Targeting lipid GPCRs to treat type 2 diabetes mellitus - progress and challenges, Nat Rev Endocrinol, 17, 162, 10.1038/s41574-020-00459-w Syed, 2018, Palmitic acid hydroxystearic acids activate GPR40, which is involved in their beneficial effects on glucose homeostasis, Cell Metab, 27, 419, 10.1016/j.cmet.2018.01.001 Paschoal, 2020, Positive reinforcing mechanisms between GPR120 and PPARgamma modulate insulin sensitivity, Cell Metab, 31, 1173, 10.1016/j.cmet.2020.04.020 Kimura, 2020, Free fatty acid receptors in health and disease, Physiol Rev, 100, 171, 10.1152/physrev.00041.2018 Taylor, 2007, Hypoxia and gastrointestinal disease, J Mol Med (Berl), 85, 1295, 10.1007/s00109-007-0277-z Fisher, 2013, Noninvasive monitoring of small intestinal oxygen in a rat model of chronic mesenteric ischemia, Cell Biochem Biophys, 67, 451, 10.1007/s12013-013-9611-y Singhal, 2020, Oxygen battle in the gut: hypoxia and hypoxia-inducible factors in metabolic and inflammatory responses in the intestine, J Biol Chem, 295, 10493, 10.1074/jbc.REV120.011188 Zheng, 2015, Physiologic hypoxia and oxygen homeostasis in the healthy intestine. A review in the theme: cellular responses to hypoxia, Am J Physiol Cell Physiol, 309, C350, 10.1152/ajpcell.00191.2015 Zeitouni, 2016, The impact of hypoxia on intestinal epithelial cell functions: consequences for invasion by bacterial pathogens, Mol Cell Pediatr, 3, 14, 10.1186/s40348-016-0041-y Glover, 2016, Oxygen metabolism and barrier regulation in the intestinal mucosa, J Clin Invest, 126, 3680, 10.1172/JCI84429 Saeedi, 2015, HIF-dependent regulation of claudin-1 is central to intestinal epithelial tight junction integrity, Mol Biol Cell, 26, 2252, 10.1091/mbc.E14-07-1194 Karhausen, 2004, Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis, J Clin Invest, 114, 1098, 10.1172/JCI200421086 Semenza, 2012, Hypoxia-inducible factors in physiology and medicine, Cell, 148, 399, 10.1016/j.cell.2012.01.021 Gonzalez, 2018, The role of hypoxia-inducible factors in metabolic diseases, Nat Rev Endocrinol, 15, 21, 10.1038/s41574-018-0096-z Bodnaruc, 2016, Nutritional modulation of endogenous glucagon-like peptide-1 secretion: a review, Nutr Metab (Lond), 13, 92, 10.1186/s12986-016-0153-3 Miyamoto, 2019, Gut microbiota confers host resistance to obesity by metabolizing dietary polyunsaturated fatty acids, Nat Commun, 10, 4007, 10.1038/s41467-019-11978-0 Ramakrishnan, 2016, Role of intestinal HIF-2alpha in health and disease, Annu Rev Physiol, 78, 301, 10.1146/annurev-physiol-021115-105202 Singhal, 2021, HIF-2alpha activation potentiates oxidative cell death in colorectal cancers by increasing cellular iron, J Clin Invest, 131, 10.1172/JCI143691 Xie, 2017, Activation of intestinal hypoxia-inducible factor 2alpha during obesity contributes to hepatic steatosis, Nat Med, 23, 1298, 10.1038/nm.4412 Song, 2019, Gut-proglucagon-derived peptides are essential for regulating glucose homeostasis in mice, Cell Metab, 30, 976, 10.1016/j.cmet.2019.08.009 Drucker, 2007, The role of gut hormones in glucose homeostasis, J Clin Invest, 117, 24, 10.1172/JCI30076 Svendsen, 2015, An analysis of cosecretion and coexpression of gut hormones from male rat proximal and distal small intestine, Endocrinology, 156, 847, 10.1210/en.2014-1710 Christensen, 2016, Glucose-dependent insulinotropic polypeptide: effects on insulin and glucagon secretion in humans, Dan Med J, 63, B5230 Chan, 2016, Tuning the transcriptional response to hypoxia by inhibiting hypoxia-inducible factor (HIF) prolyl and asparaginyl hydroxylases, J Biol Chem, 291, 20661, 10.1074/jbc.M116.749291 Keith, 2007, Hypoxia-inducible factors, stem cells, and cancer, Cell, 129, 465, 10.1016/j.cell.2007.04.019 Xiong, 2013, Activation of FFA1 mediates GLP-1 secretion in mice. Evidence for allosterism at FFA1, Mol Cell Endocrinol, 369, 119, 10.1016/j.mce.2013.01.009 Drucker, 1994, Activation of proglucagon gene transcription by protein kinase-A in a novel mouse enteroendocrine cell line, Mol Endocrinol, 8, 1646 Knepel, 1990, Transcriptional activation of the rat glucagon gene by the cyclic AMP-responsive element in pancreatic islet cells, Mol Cell Biol, 10, 6799 Chang, 2015, Ezetimibe stimulates intestinal glucagon-like peptide 1 secretion via the MEK/ERK pathway rather than dipeptidyl peptidase 4 inhibition, Metabolism, 64, 633, 10.1016/j.metabol.2015.02.001 Loboda, 2010, HIF-1 and HIF-2 transcription factors--similar but not identical, Mol Cells, 29, 435, 10.1007/s10059-010-0067-2 Kvietys, 1976, Contribution of luminal concentration of nutrients and osmolality to postprandial intestinal hyperemia in dogs, Proc Soc Exp Biol Med, 152, 659, 10.3181/00379727-152-39462 Jeays, 2007, A framework for the modeling of gut blood flow regulation and postprandial hyperaemia, World J Gastroenterol, 13, 1393, 10.3748/wjg.v13.i9.1393 Shepherd, 1982, Metabolic control of intestinal oxygenation and blood flow, Fed Proc, 41, 2084 Matheson, 2000, Regulation of intestinal blood flow, J Surg Res, 93, 182, 10.1006/jsre.2000.5862 Ramakrishnan, 2015, Maternal intestinal HIF-2alpha is necessary for sensing iron demands of lactation in mice, Proc Natl Acad Sci U S A, 112, E3738, 10.1073/pnas.1504891112 Xue, 2013, Endothelial PAS domain protein 1 activates the inflammatory response in the intestinal epithelium to promote colitis in mice, Gastroenterology, 145, 831, 10.1053/j.gastro.2013.07.010 Synnestvedt, 2002, Ecto-5'-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia, J Clin Invest, 110, 993, 10.1172/JCI0215337 Lindgren, 2011, Incretin hormone and insulin responses to oral versus intravenous lipid administration in humans, J Clin Endocrinol Metab, 96, 2519, 10.1210/jc.2011-0266 Gribble, 2019, Function and mechanisms of enteroendocrine cells and gut hormones in metabolism, Nat Rev Endocrinol, 15, 226, 10.1038/s41574-019-0168-8 Hu, 2003, Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation, Mol Cell Biol, 23, 9361, 10.1128/MCB.23.24.9361-9374.2003 Ratcliffe, 2007, HIF-1 and HIF-2: working alone or together in hypoxia?, J Clin Invest, 117, 862, 10.1172/JCI31750 Lu, 2021, Nutrient-induced cellular mechanisms of gut hormone secretion, Nutrients, 13, 883, 10.3390/nu13030883 Hira, 2020, What is GLP-1 really doing in obesity?, Trends Endocrinol Metab, 31, 71, 10.1016/j.tem.2019.09.003 Farhadipour, 2021, The function of gastrointestinal hormones in obesity-implications for the regulation of energy intake, Nutrients, 13, 1839, 10.3390/nu13061839 Nauck, 2021, GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art, Mol Metab, 46, 101102, 10.1016/j.molmet.2020.101102 Meier, 2012, GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus, Nat Rev Endocrinol, 8, 728, 10.1038/nrendo.2012.140 Brunton, 2020, GLP-1 receptor agonists in the treatment of type 2 diabetes: role and clinical experience to date, Postgrad Med, 132, 3, 10.1080/00325481.2020.1798099 Tambuwala, 2015, Targeted delivery of the hydroxylase inhibitor DMOG provides enhanced efficacy with reduced systemic exposure in a murine model of colitis, J Control Release, 217, 221, 10.1016/j.jconrel.2015.09.022 Riopel, 2020, Inhibition of prolyl hydroxylases increases hepatic insulin and decreases glucagon sensitivity by an HIF-2alpha-dependent mechanism, Mol Metab, 41, 101039, 10.1016/j.molmet.2020.101039 Ramakrishnan, 2016, HIF2alpha is an essential molecular brake for postprandial hepatic glucagon response independent of insulin signaling, Cell Metab, 23, 505, 10.1016/j.cmet.2016.01.004 Mooli, 2021, Hypoxia via ERK signaling inhibits hepatic PPARalpha to promote fatty liver, Cell Mol Gastroenterol Hepatol, 12, 585, 10.1016/j.jcmgh.2021.03.011 Mooli, 2020, Sustained mitochondrial biogenesis is essential to maintain caloric restriction-induced beige adipocytes, Metabolism, 107, 154225, 10.1016/j.metabol.2020.154225