AgRP Neurons Require Carnitine Acetyltransferase to Regulate Metabolic Flexibility and Peripheral Nutrient Partitioning
| Autor: | Brian J. Oldfield, Mathieu Méquinion, Cheng Huang, Sarah Kathleen Haas Lockie, Raphael Denis, Zane B. Andrews, Rachel E. Clarke, Ralf B. Schittenhelm, Grzegorz M Kowalski, Matthew J. Watt, Romana Stark, Serge Luquet, Jeferson F. Goularte, Alexander Reichenbach, Clinton R. Bruce, Randall L. Mynatt, Moyra B Lemus |
|---|---|
| Přispěvatelé: | Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Monash University [Clayton], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Deakin University [Burwood], Louisiana State University (LSU), ORANGE, Colette |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Proteomics EXPRESSING NEURONS medicine.medical_treatment [SDV]Life Sciences [q-bio] energy availability ACTIVATION chemistry.chemical_compound Eating substrate switch APPETITE NPY/AGRP NEURONS Insulin Agouti-Related Protein PLASTICITY glucose lcsh:QH301-705.5 Cholecystokinin chemistry.chemical_classification Mice Knockout Glucose tolerance test medicine.diagnostic_test Fatty Acids digestive oral and skin physiology Cell biology [SDV] Life Sciences [q-bio] Liver Injections Intraperitoneal MALE-MICE DIET-INDUCED OBESITY GLUCOSE-PRODUCTION fasting fatty acid utilization General Biochemistry Genetics and Molecular Biology 03 medical and health sciences medicine Animals Carnitine O-acetyltransferase Injections Intraventricular refeeding Carnitine O-Acetyltransferase Fatty acid metabolism Integrases ENERGY HOMEOSTASIS Fatty acid Reproducibility of Results Metabolism Feeding Behavior Glucose Tolerance Test 030104 developmental biology chemistry nervous system lcsh:Biology (General) Acetylation Gene Deletion RESISTANCE |
| Zdroj: | Cell Reports, Vol 22, Iss 7, Pp 1745-1759 (2018) Cell Reports Cell Reports, Elsevier Inc, 2018, 22 (7), pp.1745-1759. ⟨10.1016/j.celrep.2018.01.067⟩ Cell Reports, 2018, 22 (7), pp.1745-1759. ⟨10.1016/j.celrep.2018.01.067⟩ |
| ISSN: | 2211-1247 |
| Popis: | International audience; AgRP neurons control peripheral substrate utilization and nutrient partitioning during conditions of energy deficit and nutrient replenishment, although the molecular mechanism is unknown. We examined whether carnitine acetyltransferase (Crat) in AgRP neurons affects peripheral nutrient partitioning. Crat deletion in AgRP neurons reduced food intake and feeding behavior and increased glycerol supply to the liver during fasting, as a gluconeogenic substrate, which was mediated by changes to sympathetic output and peripheral fatty acid metabolism in the liver. Crat deletion in AgRP neurons increased peripheral fatty acid substrate utilization and attenuated the switch to glucose utilization after refeeding, indicating altered nutrient partitioning. Proteomic analysis in AgRP neurons shows that Crat regulates protein acetylation and metabolic processing. Collectively, our studies highlight that AgRP neurons require Crat to provide the metabolic flexibility to optimize nutrient partitioning and regulate peripheral substrate utilization, particularly during fasting and refeeding. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|