The Dual Burden of Hepatotoxicity and Hormonal Abnormalities in Obesity: Implications for Diabetes and Cardiovascular Risk

Obesity is a global health crisis that significantly elevates the risk of type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and liver injury. Beyond excess adiposity, obesity generates a complex interplay between hepatotoxicity and hormonal abnormalities that fuels metabolic dysfunction. Hepatic injury arises from lipotoxicity, oxidative stress, mitochondrial dysfunction, and immune activation, progressing from steatosis to steatohepatitis and fibrosis. Concurrently, hormonal imbalances, including insulin resistance, leptin resistance, hypoadiponectinemia, and altered sex steroid signaling, exacerbate energy dysregulation and cardiovascular strain. These two processes are not independent; rather, hepatotoxicity amplifies endocrine disruption by impairing insulin clearance and adipokine signaling, while hormonal disturbances aggravate hepatic injury through altered lipid metabolism and inflammatory cascades. Together, they accelerate the trajectory toward T2DM, atherosclerosis, and heart failure. This review synthesizes current knowledge on the dual burden of hepatotoxicity and hormonal imbalance in obesity, explores mechanistic intersections, and highlights clinical implications for diabetes and cardiovascular risk. Emerging biomarkers, lifestyle and pharmacologic interventions, and integrated therapeutic strategies are discussed to provide a framework for mitigating these interconnected burdens in high-risk populations. Keywords: obesity, hepatotoxicity, hormonal imbalance, diabetes, cardiovascular risk