Triiodothyronine (T3) differentially regulates thermogenic and metabolic programs in murine white, brown, and beige adipocytes

Thyroid hormone plays a central role in energy metabolism and thermogenesis, but adipocyte-intrinsic responses to triiodothyronine (T3) across adipocyte lineages remain incompletely defined. Here, we compared the transcriptional and functional responses of differentiated murine white (3T3-F442A), brown (EB5), and beige (EB7) adipocytes to sustained T3 exposure under defined in vitro conditions. T3 increased Thrb and Dio2 expression in brown and beige adipocytes, but not in white adipocytes. It also produced lineage-specific patterns of gene regulation. The thermogenic genes Ppargc1a and Ucp1 were strongly induced in brown and beige adipocytes, whereas white adipocytes showed minimal responses. Genes involved in lipid and carbohydrate metabolism were also differentially regulated: brown and beige adipocytes exhibited a pattern consistent with metabolic support of thermogenesis, while white adipocytes displayed a distinct, less thermogenically oriented response. Functional analysis showed preserved β-adrenergic lipolytic competence in T3-treated adipocytes, linking transcriptional responses to metabolic function. These findings demonstrate that sustained T3 exposure elicits adipocyte-intrinsic, lineage-dependent responses and suggest that thyroid hormone favours metabolic programs supporting energy expenditure in brown and beige adipocytes, while exerting distinct effects in white adipocytes more consistent with energy storage than thermogenic activation.