Deficiency of leptin receptor in myeloid cells disrupts hypothalamic metabolic circuits and causes body weight increase
| Autor: | Andries Kalsbeek, Nikita L. Korpel, Susanna M. Hofmann, Irina Milanova, Yuanqing Gao, Andrés Vidal-Itriago, Robby Zachariah Tom, Martin J. T. Kalsbeek, Chun-Xia Yi |
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| Přispěvatelé: | Netherlands Institute for Neuroscience (NIN), AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ANS - Cellular & Molecular Mechanisms, Endocrinology, Endocrinology Laboratory, APH - Aging & Later Life, ACS - Diabetes & metabolism |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
lcsh:Internal medicine medicine.medical_specialty media_common.quotation_subject Adipose tissue Hyperphagia Biology Weight Gain Energy homeostasis Mice 03 medical and health sciences 0302 clinical medicine Phagocytosis Internal medicine medicine Animals Myeloid Cells lcsh:RC31-1245 Microglia Diabetes Obesity Pomc Alpha-msh Molecular Biology Cells Cultured media_common Arc (protein) Leptin receptor Leptin digestive oral and skin physiology Arcuate Nucleus of Hypothalamus Appetite Cell Biology 030104 developmental biology medicine.anatomical_structure Endocrinology nervous system Hypothalamus Receptors Leptin Corrigendum hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Paraventricular Hypothalamic Nucleus |
| Zdroj: | Mol. Metab. 7, 155-160 (2017) Molecular Metabolism, 7, 155-160. Elsevier B.V. Molecular metabolism, 7, 155-160. Elsevier GmbH Molecular Metabolism, Vol 7, Iss, Pp 155-160 (2018) |
| ISSN: | 2212-8778 |
| DOI: | 10.1016/j.molmet.2017.11.003 |
| Popis: | Objective: Leptin is a cytokine produced by adipose tissue that acts mainly on the hypothalamus to regulate appetite and energy homeostasis. Previous studies revealed that the leptin receptor is expressed not only in neurons, but also in glial cells. Microglia are resident immune cells in the brain that play an essential role in immune defense and neural network development. Previously we reported that microglial morphology and cytokine production are changed in the leptin receptor deficient db/db mouse, suggesting that leptin's central effects on metabolic control might involve signaling through microglia. In the current study, we aimed to uncover the role of leptin signaling in microglia in systemic metabolic control. Methods: We generated a mouse model with leptin receptor deficiency, specifically in the myeloid cells, to determine the role of microglial leptin signaling in the development of metabolic disease and to investigate microglial functions. Results: We discovered that these mice have increased body weight with hyperphagia. In the hypothalamus, pro-opiomelanocortin neuron numbers in the arcuate nucleus (ARC) and α-MSH projections from the ARC to the paraventricular nucleus (PVN) decreased, which was accompanied by the presence of less ramified microglia with impaired phagocytic capacity in the PVN. Conclusions: Myeloid cell leptin receptor deficient mice partially replicate the db/db phenotype. Leptin signaling in hypothalamic microglia is important for microglial function and a correct formation of the hypothalamic neuronal circuit regulating metabolism. Author Video: Author Video Watch what authors say about their articles Keywords: Microglia, Diabetes, Obesity, POMC, α-MSH |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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