Spot‐14 and its paralog Spot‐14<scp>R</scp> regulate expression of metabolic and thermogenic pathway genes in murine brown and beige adipocytes

Spot 14 (S14), encoded by Thrsp, is a thyroid hormone-responsive transcriptional activator that regulates lipogenesis, though its mechanisms remain unclear. We aimed to study the role of S14 on gene expression in adipocytes. We analyzed Thrsp and its paralog Mid1ip1 in brown (EB5), beige (EB7), and white (F442A) adipocytes. Thrsp expression was higher in EB5 and EB7 than in F442A and increased with thyroid hormone T3 in EB5 and EB7 but decreased in F442A. Mid1ip1 expression rose moderately in EB5 and EB7, influencing lipid metabolism genes. Silencing Thrsp upregulated Mid1ip1 in EB7 and reduced thermogenic gene expression in EB5 and EB7. These findings underscore the roles of Thrsp and Mid1ip1 in metabolic and thermogenic pathways, highlighting the responsiveness of S14 to thyroid hormones and nutrient signals. Impact statement This study reveals that Thyroid Hormone-Induced Protein 8 (THRSP), also known as Spot-14, and its paralog Spot-14R, regulate metabolic and thermogenic gene expression differently in brown and beige adipocytes. These findings provide insights into adipocyte metabolism, offering potential targets for obesity and metabolic disorder treatments.