Related Experiment Video
Updated: Sep 22, 2025
Live Images of GLUT4 Protein Trafficking in Mouse Primary Hypothalamic Neurons Using Deconvolution Microscopy
Published on: December 7, 2017
Long-term priming of hypothalamic microglia is associated with energy balance disturbances under diet-induced obesity
María Del Mar Fernández-Arjona1,2, Ana León-Rodríguez1,3, Jesús M Grondona1,3
1Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain.
Abstract:
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.
Insights
Acute neuroinflammation primes hypothalamic microglia, altering energy balance. This priming leads to changes in microglia, affecting appetite and body weight regulation, even months after the initial event.
Area of Science:
- Neuroimmunology
- Metabolic regulation
- Neuroinflammation
Background:
- Microglia, the immune cells of the brain, can become primed by inflammation.
- Primed microglia exhibit an exaggerated response to subsequent stimuli.
- Hypothalamic microglia play a crucial role in regulating energy balance.
Purpose of the Study:
- To investigate hypothalamic microglia priming following acute neuroinflammation.
- To determine the consequences of this priming on energy balance regulation.
- To assess the long-term effects of neuroinflammation on hypothalamic function.
Main Methods:
- Intracerebroventricular administration of neuraminidase (NA) to induce acute neuroinflammation.
- Assessing microglial response in the arcuate nucleus after high-fat diet (HFD) challenge.
- In vitro LPS challenge of microglia from NA-treated mice.
- Evaluating effects of prior NA exposure on HFD-induced obesity model.
Main Results:
- Neuraminidase (NA) induced primed microglia in the hypothalamus 3 months post-injection.
- NA-treated mice exhibited heightened microglial responses to HFD and LPS challenges.
- Prior NA exposure altered energy balance, increasing food intake but reducing body weight.
- Enhanced microgliosis and reduced POMC neurons were observed in NA-treated mice under HFD conditions.
Conclusions:
- A single neuroinflammatory event can induce sustained microglia priming in the hypothalamus.
- Hypothalamic microglia priming impacts energy balance and neuronal populations.
- Neuroinflammation disrupts hypothalamic cytoarchitecture and regulatory functions, affecting nutritional challenges.
