Hypothalamic transcriptomic response to High-Fat Diet induced obesity: modulatory effects of Resveratrol, Curcumin, and Aged Garlic Extract.

Obesity is a multifaceted disorder driven by the dysregulation of homeostatic mechanisms in the hypothalamus, often resulting from dietary-induced lipotoxicity and chronic neuroinflammation. This research investigates the transcriptomic shifts in the hypothalamus during the progression of High-Fat Diet (HFD) induced obesity in juvenile male C57BL/6 mice. Mice were subjected to an 8-week HFD protocol (60% kcal from fat) starting at 8 weeks of age to establish a robust obese phenotype. We explored the therapeutic efficacy of three bioactive compounds known for their antioxidant and anti-inflammatory activities: Resveratrol (2.25 mg/kg), Curcumin (50 mg/kg), and Aged Garlic Extract (200 mg/kg), administered daily during the last four weeks of the study. Through high-throughput RNA sequencing (RNA-seq), we aim to elucidate how these compounds mitigate HFD-induced transcriptomic perturbations. This study offers critical insights into the molecular basis of obesity-related neuroinflammation and identifies specific gene clusters that can be targeted by bioactive-rich dietary strategies to counteract hypothalamic dysfunction. https://doi.org/10.3390/genes17030297