High-fat and high-sucrose diet-induced hypothalamic inflammation shows sex specific features in mice

Background

Sex differences in obesity can be observed in the etiology of this complex chronic disease, its prevalence, but also in aspects like body composition, fat distribution and hormonal action. The arcuate nucleus (Arc) is a brain region in the hypothalamus with high importance in obesity as it connects the central nervous system and endocrine system. From neuroimaging studies trying to identify potential biomarkers in patients to cell morphology and electrophysiology experiments in animal models, there is sufficient proof of abnormal neuroimmune (chain) reactions in obesity. However, the sex specific features of hypothalamic inflammation still remain unclear. In this preprint, De Paula and colleagues report sex differences in the arcuate nucleus induced by a high-fat and high-sucrose diet (HFHSD).

Key findings

After 3 days of following a strict high-fat and high-sucrose diet, different cytokines were activated in the arcuate nucleus between male and female mice; even the same cytokines showed different trends. Moreover, after 24 weeks of HFHSD, sex differences were observed in gliosis as well, with females exhibiting astrogliosis in addition to the microgliosis observed in both sexes (table 1). The inflammation in female mice seemed neither intense nor long-lasting, given that 8 weeks of chow diet following the HFHSD could reverse it.

 

Table 1.  Neuroinflammation in the hypothalamus of male and female mice after different durations of following a high-fat and high-sucrose diet

 

Importance

This detailed comparison characterizing neuroinflammation in obese mice at multiple levels provides valuable insights into the mechanisms of obesity involving the hypothalamus, with a specific emphasis on sexual dimorphisms. The observation of gliosis further supports the dominant role of microglia, as previously reported, in the inflammation of the hypothalamus in obesity. Furthermore, as the authors mentioned, the exposure of Arc to circulating factors suggests a peripheral impact, presenting a new avenue for possible interventions and treatments.

 

doi: https://doi.org/10.1242/prelights.38140

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