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Nat Rev Endocrinol. 2015 Jun;11(6):339-51. doi: 10.1038/nrendo.2015.48. Epub 2015 Mar 31.

Hypothalamic innate immune reaction in obesity.

Author information

1
Institute for Diabetes and Obesity, Helmholtz Centre for Health and Environment &Technische Universität München, 85748, Munich, Germany.
2
Department of Neuropathology, Charité, Universitätsmedizin Berlin, 10117 Berlin, Germany.
3
Institute of Anatomy, University of Leipzig, Liebigstr. 13, 04103 Leipzig, Germany.
4
Institute of Neuropathology, University of Freiburg, Breisacher Str. 64, D-79106 Freiburg, Germany.
5
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands.

Abstract

Findings from rodent and human studies show that the presence of inflammatory factors is positively correlated with obesity and the metabolic syndrome. Obesity-associated inflammatory responses take place not only in the periphery but also in the brain. The hypothalamus contains a range of resident glial cells including microglia, macrophages and astrocytes, which are embedded in highly heterogenic groups of neurons that control metabolic homeostasis. This complex neural-glia network can receive information directly from blood-borne factors, positioning it as a metabolic sensor. Following hypercaloric challenge, mediobasal hypothalamic microglia and astrocytes enter a reactive state, which persists during diet-induced obesity. In established mouse models of diet-induced obesity, the hypothalamic vasculature displays angiogenic alterations. Moreover, proopiomelanocortin neurons, which regulate food intake and energy expenditure, are impaired in the arcuate nucleus, where there is an increase in local inflammatory signals. The sum total of these events is a hypothalamic innate immune reactivity, which includes temporal and spatial changes to each cell population. Although the exact role of each participant of the neural-glial-vascular network is still under exploration, therapeutic targets for treating obesity should probably be linked to individual cell types and their specific signalling pathways to address each dysfunction with cell-selective compounds.

PMID:
25824676
DOI:
10.1038/nrendo.2015.48
[Indexed for MEDLINE]

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