Hypothalamic Neuroinflammation as a Mechanistic Link Between Dietary High-Fat Exposure and Reproductive Axis Dysfunction in an Animal Model Relevant to Nigerian Dietary Patterns

Background: The escalating consumption of high-fat diets in Nigeria, driven by increased palm oil processing, fast food proliferation, and changing dietary cultures, coincides with rising rates of anovulation and male reproductive dysfunction. Hypothalamic neuroinflammation has been proposed as a mechanistic bridge between dietary lipid excess and reproductive neuroendocrine disruption, yet no animal model study has been designed to reflect Nigerian macronutrient dietary patterns. Objectives: This study aims to establish a rodent model fed a diet mimicking Nigerian high-fat dietary patterns, characterise hypothalamic neuroinflammatory signalling through NF-kappaB, interleukin-1 beta, and microglial activation, and determine downstream impacts on gonadotrophin-releasing hormone pulsatility, luteinising hormone secretion, and gonadal steroidogenesis in both sexes. Methods: Sixty Wistar rats of each sex will be divided into high-fat diet, standard diet, and caloric restriction control groups. After 16 weeks, hypothalami will be harvested for ELISA, immunohistochemistry, and western blot analysis. Serum reproductive hormones will be quantified. Gonadotrophin-releasing hormone pulsatility will be assessed by portal blood microdialysis. Data will be analysed by two-way ANOVA with Tukey post-hoc tests. Expected Outcomes: High-fat-fed animals are expected to demonstrate significant hypothalamic microglial activation, disrupted gonadotrophin-releasing hormone pulsatility, and suppressed gonadal steroidogenesis proportional to inflammatory signalling intensity. Conclusion: This study will generate original mechanistic evidence linking Nigerian dietary trends to reproductive neuroendocrine disruption. Keywords: hypothalamic neuroinflammation, high-fat diet, reproductive axis, gonadotrophin-releasing hormone, NF-kappaB.