Distinct effects of physical and functional ablation of brown adipose tissue on T3-dependent pathological cardiac remodeling

Abstract

Heart failure tends to deteriorate in colder climates, heightening the risk of major adverse cardiovascular events. Brown adipose tissue (BAT) serves as both a thermogenic organ and an atypical site for triiodothyronine (T3) synthesis in response to cold. This study investigates the potential role of BAT in contributing to abdominal aortic constriction (AAC)-induced pathological cardiac remodeling during cold exposure. In this study, we developed a mouse model of pathological cardiac remodeling using AAC. Physical excision of interscapular BAT (iBATx) was performed during cold exposure, and T3 synthesis levels were measured. Additionally, the impact of uncoupling protein 1 (UCP1) knockout on thermogenic function and pathological cardiac remodeling was investigated. In vitro studies were conducted to assess the effect of T3 on cardiomyocyte hypertrophy induced by phenylephrine (PE). Physical removal of interscapular BAT during cold exposure decreased T3 synthesis and mitigated pathological cardiac remodeling. Conversely, UCP1 knockout eliminated thermogenic function during cold exposure, while preserving BAT integrity increased T3 synthesis and exacerbated pathological cardiac remodeling. In vitro, T3 further aggravated cardiomyocyte hypertrophy caused by PE. These findings underscore the distinct effects of physical and functional BAT ablation on pathological cardiac remodeling, primarily through altering T3 levels rather than thermogenesis in cold environments. This research provides new insights into the differential roles of BAT in cardiac health, particularly under cold exposure conditions.