Xian (Eddie) Sun

Obesity is a serious health issue that can lead to life-threatening comorbidities and economic burdens. It is known that the development of obesity and associated syndromes is influenced by an individual's sex, and the hypothalamus is a major contributor to obesity. The consumption of energy-dense diet induces a pro-inflammatory response in glia, which is characterized by the presence of gliosis. However, whether hypothalamic glia adaptations to nutritional challenges contribute to the sex-dimorphic development of obesity remains unknown. In the present study, we have explored 1) the development of systemic metabolic disbalances after consumption of a high-caloric diet, and 2) the development of diet-induced gliosis within and extra hypothalamic areas in a sex-dependent manner. We have investigated systemic metabolism and glia morphological changes after a short (ST, 5 days) or long-term (LT, 1 month) exposure to a high-fat high-sugar (HFHS) diet in male and female mice. Brain slices of the lateral hypothalamus (LH), arcuate nucleus (ARC), nucleus accumbens (Nac), and pre-frontal cortex (PFC) were stained by immunofluorescence, and images of glia reactivity markers were imaged by confocal microscopy. We have found a specific increase in body weight and GFAP and Iba-1 IR only in hypothalamic areas (ARC, LH) in male mice after a ST exposure to HFHS diet, but no differences in Nac and PFC. In addition, a decreased number of S100b positive astrocytes was found in the ARC, LH, and PFC after a ST exposure to HFHS diet. On the other hand, LT exposure to a HFHS diet overruled metabolic sex-differences as similar BW increases were observed in both female and male groups. Our findings suggest that male mice are more vulnerable to the development of obesity-related metabolic dysregulation and associated gliosis in the hypothalamus compared to female mice. Moreover, dietary exposure to HFHS elicited gliosis in specific brain areas, suggesting region-specific glia functional heterogeneity.