Transcriptomic Changes in Adult Hypothalamic Neurons Following Leptin Sensitivity Modulation

Modulating leptin sensitivity in hypothalamic neurons is critical for metabolic regulation and plays a key role in the development of obesity. This study examines the effects of three distinct approaches—leptin exposure (LEPA), leptin antagonist administration (LANTA), and palmitate treatment (PA)—on adult-derived mHypoA-2/12 neurons. Transcriptomic analysis using 3' mRNA-Seq revealed significant downregulation of several pathways, including the NOD-like receptor signaling pathway, C-type lectin receptor signaling pathway, NF-κB signaling pathway, and IL-17 signaling pathway. These pathways are closely linked to neuroinflammatory processes, suggesting that modulating leptin sensitivity may influence inflammation in the hypothalamus. The observed downregulation indicates a complex interaction between leptin signaling and cellular stress responses, which may represent an adaptive mechanism to prolonged exposure to leptin or fatty acids. Understanding these dynamics is crucial for gaining insight into how neuroinflammation contributes to the development of leptin resistance and related metabolic disorders.