The iminosugar AMP-DNM improves satiety and activates brown adipose tissue through GLP1
| Autor: | Cindy P. A. A. van Roomen, Ewout Foppen, Mina Mirzaian, Sander Kooijman, Saskia Scheij, Herman S. Overkleeft, Chun-Xia Yi, Roelof Ottenhoff, Marco van Eijk, Clarita Mergen, Patrick C.N. Rensen, Yanan Wang, Kirstin Jansen, Daniela Herrera Moro Chao, Matthias H. Tschöp, Johannes M. F. G. Aerts, Edwin T. Parlevliet, Marri Verhoek, Dawei Wang, André Marques, Rolf G. Boot, Andries Kalsbeek, Randy J. Seeley |
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| Přispěvatelé: | University of Zurich, Aerts, Johannes M F G, Netherlands Institute for Neuroscience (NIN), Laboratory for Endocrinology, Medical Biochemistry, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, AGEM - Endocrinology, metabolism and nutrition, Amsterdam Gastroenterology Endocrinology Metabolism, Endocrinology, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Cardiovascular Sciences, APH - Aging & Later Life |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty 1-Deoxynojirimycin Endocrinology Diabetes and Metabolism Iminosugar Adipose tissue Adamantane 610 Medicine & health 030209 endocrinology & metabolism Satiation Carbohydrate metabolism Mice 03 medical and health sciences Endocrinology 0302 clinical medicine Adipose Tissue Brown Glucagon-Like Peptide 1 10183 Swiss Institute of Allergy and Asthma Research Internal medicine Brown adipose tissue Internal Medicine medicine Animals Glucose homeostasis Secretion Obesity Rats Wistar Receptor business.industry Antagonist Brain Rats Mice Inbred C57BL Diabetes and Metabolism 2712 Endocrinology Diabetes and Metabolism Glucose 030104 developmental biology medicine.anatomical_structure 2724 Internal Medicine business Signal Transduction |
| Zdroj: | Diabetes, 68(12), 2223-2234. AMER DIABETES ASSOC Diabetes 68, 2223-2234 (2019) Diabetes, 68(12), 2223-2234 Diabetes, 68, 2223-2234. American Diabetes Association Inc. Diabetes, 68(12), 2223-2234. American Diabetes Association Inc. |
| ISSN: | 0012-1797 |
| Popis: | Obesity is taking on worldwide epidemic proportions, yet effective pharmacological agents with long-term efficacy remain unavailable. Previously, we designed the iminosugar N-adamantine-methyloxypentyl-deoxynojirimycin (AMP-DNM), which potently improves glucose homeostasis by lowering excessive glycosphingolipids. Here we show that AMP-DNM promotes satiety and activates brown adipose tissue (BAT) in obese rodents. Moreover, we demonstrate that the mechanism mediating these favorable actions depends on oral, but not central, administration of AMP-DNM, which ultimately stimulates systemic glucagon-like peptide 1 (GLP1) secretion. We evidence an essential role of brain GLP1 receptors (GLP1r), as AMP-DNM fails to promote satiety and activate BAT in mice lacking the brain GLP1r as well as in mice treated intracerebroventricularly with GLP1r antagonist exendin-9. In conclusion, AMP-DNM markedly ameliorates metabolic abnormalities in obese rodents by restoring satiety and activating BAT through central GLP1r, while improving glucose homeostasis by mechanisms independent of central GLP1r. |
| Databáze: | OpenAIRE |
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