Atraric acid alleviates high-fat diet-induced cardiac injury via eEF2K.

A high-fat diet (HFD) is a major contributor to metabolic diseases, causing cardiac injury through inflammation, oxidative stress, and apoptosis mechanisms. Atraric acid (AA) is a natural compound with anti-inflammatory and metabolic regulatory activities; however, its protective effects against HFD-induced cardiac injury and the underlying mechanisms remain unclear. This study aimed to investigate whether AA alleviates HFD-induced cardiac injury by regulating eukaryotic elongation factor 2 kinase (eEF2K). Using an HFD-induced mouse model and a primary cardiomyocytes (PCMs) model established with mixed fatty acids (FA), the intervention effects of AA were evaluated from multiple perspectives, including histopathology, cardiac function parameters, and serum myocardial injury markers. The underlying mechanisms were further analyzed using techniques such as histochemical staining, qPCR, and Western blot. Results demonstrated that AA intervention significantly improved HFD-induced myocardial structural disarray, cardiac dysfunction, and elevated cardiac enzymes. Concurrently, it markedly suppressed proinflammatory factor expression, enhanced antioxidant enzyme activity, reduced oxidative product levels, and modulated apoptosis-related protein expression. Mechanistic studies revealed that AA specifically enhances eEF2K activity, and blocking eEF2K reverses AA's mitigating effects on inflammation, oxidative stress, and apoptosis, as well as its protective effects on cell viability. In summary, AA may mitigate HFD-induced cardiac injury by activating the eEF2K signaling pathway to synergistically suppress inflammatory responses, oxidative damage, and apoptosis. This provides a potential drug target and novel therapeutic strategy for the prevention and treatment of metabolic-related cardiac diseases.