• Metabolic reprogramming is a primary driver of disease initiation, progression, and therapeutic resistance, not just a passive consequence.
• Multi-omics approaches reveal tissue-specific metabolic shifts underlying cardiometabolic syndrome, offering new therapeutic targets beyond symptom management.
• In pregnancy, skeletal muscle undergoes structural and metabolic reprogramming, linking maternal insulin resistance to gestational diabetes mellitus.
• Levosimendan protects against septic cardiomyopathy via Nrf2-dependent mitochondrial preservation, highlighting metabolic interventions for acute organ injury.