Sex-Dependent S1P-Related Gene Expression in Brown Adipose Tissue Across Exercise and Thermal Conditions

Sphingosine-1-phosphate (S1P) signaling has emerged as a regulator of metabolic homeostasis, but its relationship to brown adipose tissue (BAT) adaptation across physiological conditions remains unclear. We examined how S1P-related gene expression in BAT and subcutaneous white adipose tissue (scWAT) varies with acute exercise, chronic exercise, ambient temperature, aging, sex, and UCP1 deficiency. Young and aged wild-type mice, as well as aged UCP1 knockout (UCP1KO) mice, were studied across acute or chronic exercise paradigms and thermal conditions ranging from 4 °C to 30 °C. In BAT, acute exercise was associated with lower S1pr1, S1pr2, and Sphk1 expression in young females, whereas aged males showed lower S1pr2 and Sphk1 after exercise. In scWAT, exercise-associated induction of S1P-related transcripts was most evident in aged males. Female BAT also displayed broader temperature- and chronic exercise-associated differences in S1pr2, Sphk1, and β-adrenergic receptor transcripts, whereas male BAT showed fewer transcriptional changes. In UCP1KO mice, these exercise-associated patterns were altered or attenuated. Together, these findings identify a context-dependent adipose S1P-related transcriptional program that differs by sex, age, depot, ambient temperature, exercise condition, and UCP1 status.