RT Journal Article
T1 Long-term priming of hypothalamic microglia is associated with energy balance disturbances under diet-induced obesity.
A1 Fernández-Arjona, María Del Mar
A1 León-Rodríguez, Ana
A1 Grondona, Jesús M
A1 López-Ávalos, María D
K1 MHCII
K1 high fat diet
K1 hypothalamus
K1 microglia priming
K1 neuraminidase
K1 neuroinflammation
K1 obesity
AB Exposure of microglia to an inflammatory environment may lead to their priming and exacerbated response to future inflammatory stimuli. Here we aimed to explore hypothalamic microglia priming and its consequences on energy balance regulation. A model of intracerebroventricular administration of neuraminidase (NA, which is present in various pathogens such as influenza virus) was used to induce acute neuroinflammation. Evidences of primed microglia were observed 3 months after NA injection, namely (1) a heightened response of microglia located in the hypothalamic arcuate nucleus after an in vivo inflammatory challenge (high fat diet [HFD] feeding for 10 days), and (2) an enhanced response of microglia isolated from NA-treated mice and challenged in vitro to LPS. On the other hand, the consequences of a previous NA-induced neuroinflammation were further evaluated in an alternative inflammatory and hypercaloric scenario, such as the obesity generated by continued HDF feeding. Compared with sham-injected mice, NA-treated mice showed increased food intake and, surprisingly, reduced body weight. Besides, NA-treated mice had enhanced microgliosis (evidenced by increased number and reactive morphology of microglia) and a reduced population of POMC neurons in the basal hypothalamus. Thus, a single acute neuroinflammatory event may elicit a sustained state of priming in microglial cells, and in particular those located in the hypothalamus, with consequences in hypothalamic cytoarchitecture and its regulatory function upon nutritional challenges.
YR 2022
FD 2022-05-23
LK http://hdl.handle.net/10668/21951
UL http://hdl.handle.net/10668/21951
LA en
DS RISalud
RD Apr 8, 2025