المؤلفون: Christina N. Heiss, Randy J. Seeley, Ying Shiuan Lee, Fredrik Bäckhed, Anna Håkansson Gladh, Daniel J. Drucker, Louise Mannerås-Holm, Julia Serrano-Lobo, Louise E. Olofsson

المصدر: Heiss, C N, Mannerås-Holm, L, Lee, Y S, Serrano-Lobo, J, Håkansson Gladh, A, Seeley, R J, Drucker, D J, Bäckhed, F & Olofsson, L E 2021, ' The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism ', Cell Reports, vol. 35, no. 8, 109163 . https://doi.org/10.1016/j.celrep.2021.109163Test

مصطلحات موضوعية: Leptin, Male, 0301 basic medicine, endocrine system, medicine.medical_specialty, diet-induced obesity, Hypothalamus, microglia, Gut flora, Glucagon-Like Peptide-1 Receptor, General Biochemistry, Genetics and Molecular Biology, leptin sensitivity, Mice, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Animals, Humans, Obesity, Receptor, hypothalamic inflammation, Inflammation, gut microbiota, Glial fibrillary acidic protein, biology, Microglia, digestive, oral, and skin physiology, astrocytes, biology.organism_classification, medicine.disease, Glucagon-like peptide-1, Gastrointestinal Microbiome, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, glucagon-like peptide-1, Diet, Western, biology.protein, medicine.symptom, GLP-1, Weight gain, hormones, hormone substitutes, and hormone antagonists, 030217 neurology & neurosurgery

الوصف: Mice lacking a microbiota are protected from diet-induced obesity. Previous studies have shown that feeding a Western diet causes hypothalamic inflammation, which in turn can lead to leptin resistance and weight gain. Here, we show that wild-type (WT) mice with depleted gut microbiota, i.e., germ-free (GF) and antibiotic-treated mice, have elevated levels of glucagon-like peptide-1 (GLP-1), are protected against diet-induced hypothalamic inflammation, and have enhanced leptin sensitivity when fed a Western diet. Using GLP-1 receptor (GLP-1R)-deficient mice and pharmacological inhibition of the GLP-1R in WT mice, we demonstrate that intact GLP-1R signaling is required for preventing hypothalamic inflammation and enhancing leptin sensitivity. Furthermore, we show that astrocytes express the GLP-1R, and deletion of the receptor in glial fibrillary acidic protein (GFAP)-expressing cells diminished the antibiotic-induced protection against diet-induced hypothalamic inflammation. Collectively, our results suggest that depletion of the gut microbiota attenuates diet-induced hypothalamic inflammation and enhances leptin sensitivity via GLP-1R-dependent mechanisms.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1246c48efc4ba88cddca0f7c9a69b5f7Test
https://doi.org/10.1016/j.celrep.2021.109163Test

المؤلفون: Carolyn F. Deacon, Reidar Albrechtsen, Rune E. Kuhre, Lasse Bremholm, Charlotte Janus, Elisa P. Jensen, Nicolai J. Wewer Albrechtsen, Linda Hilsted, Steen Seier Poulsen, Berit Svendsen, C. Christiansen, Jens J. Holst, Bolette Hartmann

المصدر: Albrechtsen, N J W, Albrechtsen, R, Bremholm, L, Svendsen, B, Kuhre, R E, Poulsen, S S, Christiansen, C B, Jensen, E P, Janus, C, Hilsted, L, Deacon, C F, Hartmann, B & Holst, J J 2016, ' Glucagon-like peptide-1 receptor signaling in acinar cells causes growth dependent release of pancreatic enzymes ', Cell Reports, vol. 17, no. 11, pp. 2845-2856 . https://doi.org/10.1016/j.celrep.2016.11.051Test

مصطلحات موضوعية: 0301 basic medicine, endocrine system, medicine.medical_specialty, Incretin, 030209 endocrinology & metabolism, Acinar Cells, Incretins, Gene Expression Regulation, Enzymologic, Glucagon-Like Peptide-1 Receptor, General Biochemistry, Genetics and Molecular Biology, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Glucagon-Like Peptide 1, Internal medicine, medicine, Animals, Humans, Amylase, Epidermal growth factor receptor, Receptor, Pancreas, Cell Proliferation, biology, Forkhead Box Protein O1, digestive, oral, and skin physiology, Lipase, medicine.disease, Glucagon-like peptide-1, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 2, Pancreatitis, Amylases, Pancreatic juice, biology.protein, Signal transduction, hormones, hormone substitutes, and hormone antagonists, Signal Transduction

الوصف: Incretin-based therapies are widely used for type 2 diabetes and now also for obesity, but they are associated with elevated plasma levels of pancreatic enzymes and perhaps a modestly increased risk of acute pancreatitis. However, little is known about the effects of the incretin hormone glucagon-like peptide 1 (GLP-1) on the exocrine pancreas. Here, we identify GLP-1 receptors on pancreatic acini and analyze the impact of receptor activation in humans, rodents, isolated acini, and cell lines from the exocrine pancreas. GLP-1 did not directly stimulate amylase or lipase release. However, we saw that GLP-1 induces phosphorylation of the epidermal growth factor receptor and activation of Foxo1, resulting in cell growth with concomitant enzyme release. Our work uncovers GLP-1-induced signaling pathways in the exocrine pancreas and suggests that increases in amylase and lipase levels in subjects treated with GLP-1 receptor agonists reflect adaptive growth rather than early-stage pancreatitis.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a43e7682a70527e6c33c012213932100Test
https://doi.org/10.1016/j.celrep.2016.11.051Test

المؤلفون: Erin E. Mulvihill, Laurie L. Baggio, Daniel J. Drucker, Elodie M. Varin, Jacqueline A. Koehler, Randy J. Seeley, Xiemin Cao

المصدر: Cell Reports, Vol 27, Iss 11, Pp 3371-3384.e3 (2019)

مصطلحات موضوعية: 0301 basic medicine, Nervous system, Male, medicine.medical_specialty, Recombinant Fusion Proteins, Glucagon-Like Peptides, Incretin, Wnt1 Protein, Biology, Incretins, General Biochemistry, Genetics and Molecular Biology, Energy homeostasis, Glucagon-Like Peptide-1 Receptor, 03 medical and health sciences, Eating, Mice, 0302 clinical medicine, Glucagon-Like Peptide 1, Internal medicine, medicine, Glucose homeostasis, Animals, Homeostasis, Receptor, lcsh:QH301-705.5, 2. Zero hunger, Homeodomain Proteins, Neurons, Gastric emptying, digestive, oral, and skin physiology, Brain, Glucagon-like peptide-1, Immunoglobulin Fc Fragments, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Glucose, lcsh:Biology (General), Gastric Emptying, Enteric nervous system, 030217 neurology & neurosurgery, Transcription Factors

الوصف: Summary: Glucagon-like peptide 1 (GLP-1) receptors are widely distributed throughout the nervous system, enabling physiological and pharmacological control of glucose and energy homeostasis. Here we elucidated the importance of Glp1r expression within cellular domains targeted by expression of Wnt1-Cre2 or Phox2b-Cre. Widespread loss of neural Glp1r in Glp1rΔWnt1−/− mice had no effect on basal food intake, gastric emptying, and glucose homeostasis. However, the glucoregulatory actions of GLP-1R agonists, but not gut-selective DPP-4 inhibition, were preserved in Glp1rΔWnt1−/− mice. Unexpectedly, selective reduction of Glp1r expression within neurons targeted by Phox2b-Cre impaired glucose homeostasis and gastric emptying and attenuated the extent of weight loss achieved with sustained GLP-1R agonism. Collectively, these studies identify discrete neural domains of Glp1r expression mediating GLP-1-regulated control of metabolism and the gut-brain axis and reveal the unexpected importance of neuronal Phox2b+ cells expressing GLP-1R for physiological regulation of gastric emptying, islet hormone responses, and glucose homeostasis. : Varin et al. use Wnt1-Cre2 and Phox2b-Cre to target distinct GLP-1R+ neuronal populations with different roles in physiological versus pharmacological control of food intake, glucose homeostasis, gastric emptying, and the gut-brain glucoregulatory axis. Keywords: glucagon-like peptide 1, brain, metabolism, gut hormones, obesity, enteric nervous system, type 2 diabetes

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e08b49278dc05d955ee4b254135fe406Test
https://pubmed.ncbi.nlm.nih.gov/31189118Test