Systemic, tissue-specific, and serum metabolic profiles were analyzed, with a particular focus on lipid abnormalities in the liver and adipose tissues.<h4>Results</h4>Npffr2 overexpression exacerbated obesity-induced metabolic dysfunction, including accelerated body weight gain, impaired glucose homeostasis, altered fat composition, adipose tissue inflammation, and dysregulated lipid metabolism. The gene discussed is NPFFR2; the disease is Obesity.