White Adipose Tissue Contributes to Cardiac Homeostasis and Adaptation to Cardiometabolic Stress in a Sex- and Depot-Specific Manner.

BACKGROUND: White adipose tissue (WAT) is increasingly recognized as an endocrine organ involved in cardiovascular physiology. However, the specific contributions of distinct adipose depots to cardiac homeostasis and adaptation to pathological stress remain poorly understood. We investigated the consequences of visceral (VAT) or subcutaneous (SAT) lipectomy (Lpx) on cardiac phenotype in male and female C57BL/6J mice and evaluated its impact on the response to a stress-inducing heart failure with preserved ejection fraction-like phenotype. METHODS: VAT or SAT depot removal was performed in young adult mice. Ten weeks later, we assessed cardiac morphology, function, circulating adipokines, and left ventricular (LV) gene expression. We then exposed separate cohorts to angiotensin II infusion combined with a high-fat diet. We also conducted experiments in ovariectomized (Ovx) females to evaluate the contribution of ovarian hormones. RESULTS: Lpx induced marked depot- and sex-specific effects on body composition, cardiac morphology, and echocardiographic parameters. Changes in LV mass, atrial size, and diastolic indices were observed despite the absence of overt pathology. These alterations were accompanied by substantial modulation of genes involved in cardiac hypertrophy, calcium handling, extracellular matrix remodelling, and energy metabolism. VAT and SAT removal also differentially affected circulating adiponectin, leptin, and MCP-1 levels. Lpx modified the cardiac hypertrophic response to cardiometabolic stress in a sex- and depot-dependent manner. Ovx altered several of these responses and was associated with evidence of increased pulmonary congestion in VAT-lipectomized females. CONCLUSIONS: These findings show that WAT contributes to maintaining cardiac homeostasis and influences adaptation to pathological stress through mechanisms highly dependent on adipose depot location, biological sex, and ovarian hormone status.