Astrocytic pyruvate dehydrogenase kinase-2 is involved in hypothalamic inflammation in mouse models of diabetes
| Autor: | Inkyu Lee, Habibur Rahman, Jae-Hong Kim, Il-Sung Jang, Kyoungho Suk, Mithilesh Kumar Jha, Younghoon Go, Anup Bhusal, Gyun Jee Song |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pyruvate dehydrogenase kinase Science Cell Hypothalamus Metabolic disorders General Physics and Astronomy Biology Molecular neuroscience General Biochemistry Genetics and Molecular Biology Energy homeostasis Article Pathogenesis 03 medical and health sciences Mice 0302 clinical medicine Diabetes mellitus medicine Diabetes Mellitus Animals Obesity lcsh:Science Inflammation Multidisciplinary Brain Diseases Metabolic Pyruvate Dehydrogenase Acetyl-Transferring Kinase General Chemistry Feeding Behavior medicine.disease Phenotype Cell biology Disease Models Animal 030104 developmental biology medicine.anatomical_structure Astrocytes lcsh:Q Signal transduction Astrocyte 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-20 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-19576-1 |
| Popis: | Hypothalamic inflammation plays an important role in disrupting feeding behavior and energy homeostasis as well as in the pathogenesis of obesity and diabetes. Here, we show that pyruvate dehydrogenase kinase (PDK)-2 plays a role in hypothalamic inflammation and its sequelae in mouse models of diabetes. Cell type-specific genetic ablation and pharmacological inhibition of PDK2 in hypothalamic astrocytes suggest that hypothalamic astrocytes are involved in the diabetic phenotype. We also show that the PDK2-lactic acid axis plays a regulatory role in the observed metabolic imbalance and hypothalamic inflammation in mouse primary astrocyte and organotypic cultures, through the AMPK signaling pathway and neuropeptidergic circuitry governing feeding behavior. Our findings reveal that PDK2 ablation or inhibition in mouse astrocytes attenuates diabetes-induced hypothalamic inflammation and subsequent alterations in feeding behavior. Hypothalamic inflammation is involved in the pathogenesis of diabetes. The underlying mechanisms are unclear. Here, the authors show that astrocytic PDK2 ablation or inhibition attenuates hypothalamic inflammation in mouse models of diabetes. |
| Databáze: | OpenAIRE |
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