Nutrient-Induced Remodeling of the Adipose-Cardiac Axis: Metabolic Flexibility, Adipokine Signaling, and Therapeutic Implications for Cardiometabolic Disease

Insulin resistance, dyslipidemia, hypertension, and visceral adiposity are the leading causes of the growing worldwide health burden associated with metabolic syndrome, obesity, and cardiovascular diseases (CVDs). Despite the "obesity paradox," which emphasizes the varied cardiovascular outcomes among obese people, obesity is now acknowledged as an active contributor to cardiometabolic dysfunction through endocrine, inflammatory, and metabolic pathways. Growing evidence indicates that nutrition is a key determinant of cardiometabolic risk, highlighting the need to understand diet-mediated mechanisms linking adipose tissue to cardiac function. Adipokines, including adiponectin, leptin, TNF-α, and resistin, which regulate systemic inflammation, metabolic homeostasis, and myocardial physiology, are secreted by adipose tissue, which is no longer thought of as passive energy storage. Its heterogeneous phenotypes, white, brown, and beige adipose tissue, exhibit distinct metabolic profiles that influence cardiac energetics and inflammatory status. Nutrient-driven transitions between these phenotypes further underscore the intricate interplay between diet, adipose biology, and cardiac metabolism. Central nutrient-sensing pathways, including mTOR, AMPK, SIRT1, PPAR-γ, and LKB1, integrate macronutrient and micronutrient signals to regulate adipose tissue remodeling and systemic metabolic flexibility. These pathways interact with hormonal mediators such as insulin, leptin, and adiponectin, forming a complex regulatory network that shapes the adipose-cardiac axis. This review synthesises current knowledge on how nutrient inputs modulate adipose tissue phenotypes and signaling pathways to influence cardiac function. By elucidating these mechanisms, we highlight emerging opportunities for precision nutrition and targeted therapeutics to restore metabolic balance, strengthen cardiac resilience, and reduce the burden of cardiometabolic disease.