Thus, we assessed the inflammatory state of different tissues and revealed that Sfrp1-/- mice fed a HFD exhibited increased macrophage infiltration and expression of pro-inflammatory markers including IL-6, Nmnat, Tgf-β2, and SerpinE1. Our findings demonstrate that the expression of Sfrp1 is a critical factor required for maintaining appropriate cellular signaling in response to the onset of obesity. This evidence concerns the gene NMNAT1 and obesity disorder.