GLIA-ReprObesity · Exploring the contribution of hypothalamic gliosis to the metabolic and reproductive complications of hypogonadism: Translational implications for obesity-induced male hypogonadism.

Exploring the contribution of hypothalamic gliosis to the metabolic and reproductive complications of hypogonadism: Translational implications for obesity-induced male hypogonadism.

Obesity has become a global epidemic and remains one of the most urgent public health challenges worldwide. Its rise has been accompanied by a marked increase in obesity related comorbidities, including type 2 diabetes, hypertension, and cardiovascular disease. Beyond these well established metabolic consequences, a growing body of evidence indicates that obesity also contributes to hypogonadism, defined in males as abnormally low endogenous testosterone levels, a reproductive disorder that further elevates metabolic risk and worsens long term health outcomes. Despite the clinical relevance of this association, the biological mechanisms linking metabolic dysfunction and reproductive impairment remain poorly understood. Recent clinical and preclinical studies associate high fat-diet consumption with hypothalamic gliosis, an inflammatory response involving microglia and astrocytes. However, whether gliosis is a driver, a consequence, or a co amplifier of hypogonadism remains unknown. This project addresses this critical knowledge gap by using microglia-, the brain’s resident immune cells, and astrocyte-specific mouse models with increased or reduced inflammatory signaling. Thus, the project will unveil the potential role of hypothalamic gliosis as a central node linking metabolic dysregulation and reproductive dysfunction. The expected impacts of this work are quite high and relevant. At the scientific level, the project will clarify a fundamental biological question with implications for endocrinology, metabolism, and neuroinflammation. At the translational level, identifying glial cells as potential upstream regulators of hypogonadism could reveal new therapeutic targets capable of mitigating both metabolic deterioration and reproductive impairment in patients with obesity.

Data: CORDIS, © European Union