Burn Injury Triggers Distinct Transcriptomic Profiles in Adipose Tissue of Adult and Aged Mice

Severe burns are a major global health concern, and are associated with long-term physical and psychological impairments, multi-organ dysfunction, and substantial morbidity and mortality. While burn injuries in adults trigger systemic immuno-metabolic alterations—characterized by white adipose tissue browning, elevated resting energy expenditure, widespread catabolism, and inflammation—these adaptive responses are considerably impaired in older adults, with molecular mechanisms behind these differences remaining largely unclear. As a key regulator of systemic metabolism, investigating the pathological role of adipose tissue (AT) postburn may reveal novel targets that could potentially improve patient outcomes. In this study, we conducted bulk mRNA sequencing and analysis of AT from adult and aged mice to elucidate the transcriptomic changes underlying the distinct postburn responses in these populations. After examining differentially expressed genes in the adult and aged burn mice, the top six upregulated genes in adults (Ucp1, Lgr6, Dio2, Lncbate10, Fabp3, Kng2) were primarily associated with thermogenesis, whereas those in the aged mice (Car6, Spata25, Gm128, Btbd16, Lipm, Abca13) were linked to inflammation, tissue repair, and lipid metabolism. Furthermore, our gene co-expression and enrichment map analysis identified burn-associated modules related to fatty acid oxidation, acetyl thioester CoA, and thermogenesis in adults, whereas leukocyte migration, tumor necrosis factor production, and sister chromatids were in aged mice. Notably, Ppara and Sfpi1 emerged as potential master regulators of co-expressed genes in burn AT of adult and aged mice, respectively. Our findings highlight age-specific differences in burn-induced AT responses and uncover potential molecular regulators that may inform targeted therapeutic strategies to mitigate the post-burn stress response.