Mitochondrial medicine in obesity: a scoping review

Introduction: Mitochondrial dysfunction connects obesity and metabolic dysfunction. We conducted a scoping review on mitochondria in obesity to (i) describe morpho-functional mitochondrial abnormalities across tissues and (ii) summarize mitochondria-directed lifestyle and pharmacological strategies and their metabolic effects. Content: PubMed and Web of Science were searched, using relevant keywords. English-language original studies, clinical trials, and systematic reviews were qualitatively synthesized in a scoping review conducted in accordance with the PRISMA extension for Scoping Reviews and prospectively registered in the Open Science Framework. Summary: Sixty primary articles and cross-references describe nutrient overload-induced oxidative stress, disturbed mitochondrial dynamics and mitophagy, and maladaptive endoplasmic reticulum (ER)-mitochondria contacts across various organ tissues and cancer. These changes are associated with insulin resistance, steatotic liver disease, chronic kidney disease, cardiovascular dysfunction, impaired fertility, and tumor progression. Reported interventions include mitochondria-targeted antioxidants, AMPK/SIRT1/PGC-1α activators, modulators of ER-mitochondria coupling, microbiota-directed approaches, and lifestyle changes. Common mitochondrial signatures, excess reactive species, impaired quality control, and altered organelle crosstalk, underlie systemic metabolic derangement, supporting mitochondria as a unifying therapeutic target. Outlook: Obesity involves widespread mitochondrial changes in various organs. Approaches that improve mitochondrial health through lifestyle and medication may help manage obesity complications and need thorough clinical testing.