Mitochondrial Medicine in Obesity: A Scoping Review

Condition or domain being studied: Insulin Resistance Rationale for the review 1. To outline the range of mitochondrial structural and functional abnormalities that characterize obesity, integrating recent ultra-structural, biochemical and omics-level findings. 2. To critically evaluate current therapeutic strategies aimed at restoring mitochondrial health, including pharmacological agents, lifestyle interventions and microbiota-based modalities, and assess their efficacy in pre-clinical and clinical settings. 3. To identify existing knowledge gaps and suggest future research priorities for utilizing mitochondrial biology in the prevention and treatment of obesity and its metabolic complications. Review objectives Summarize the concepts of lipotoxicity, immunosenescence, inflammaging, and immunometabolism in relation to mitochondria, along with mitochondrial toxicity from drugs. Emphasize the impact of mitochondrial dysfunction in adipose tissue, the liver, kidneys, pancreas, skeletal muscle, heart, female reproductive function, and cancer. Explore potential therapeutic strategies, such as dietary interventions, physical exercise, and pharmacological agents, aimed at improving mitochondrial biogenesis, quality, and function to address insulin resistance, chronic inflammation, and obesity-related disorder. Propose a research agenda to guide future investigations on the role of mitochondria in obesity. Keywords: Adipose tissue; Cancer; Gut dysbiosis; Metabolic dysfunction-associated steatotic liver disease; Oxidative stress Country: Italy; Germany Population included: Adults with obesity (as diagnosed using standard criteria). Population Exclude: Adolescents (under 18 years of age) and elderly people (over 70). Outline: Our review article will focus on providing a descriptive overview. Specifically, given the heterogeneity in study designs and outcome measures, we will conduct a qualitative synthesis by describing the phylogenesis, normal structure, and physiological energetic and signaling functions of mitochondria. Next, we will discuss alterations in mitochondrial functions during obesity, mitochondria and adipose tissue, skeletal muscle, oxidative stress, inflammageing, insulin resistance, as well as diabetes and other cardio-nephro-metabolic diseases. Additionally, we will describe general mechanisms such as mitophagy and aberrant mitochondria. Specific cell types will be discussed including adipose tissue, pancreatic beta-cells, kidneys, heart, steatotic liver disease, the female reproductive tract, and cancer. Finally, we will also discuss the relationships of mitochondria, with diets, exercise and certain drugs. Review team members Professor Amedeo Lonardo (review guarantor and contact) ORCID: 0000-0001-9886-0698. Azienda Ospedaliero-Universitaria di Modena. Italy. No conflict of interest declared. Professor Ralf Weiskirchen. ORCID: 0000-0003-3888-0931. University of Aachen, Germany. Germany. No conflict of interest declared. Named contact Professor Amedeo Lonardo (a.lonardo@libero.it). ORCID: 0000-0001-9886-0698. Azienda Ospedaliero-Universitariadi Modena. Italy. Review affiliation Ospdelae Civile di Baggiovara. Azienda Ospedliero-Univresitaria di Modena (-2023) Funding source Review has no specific/external funding but is supported by guarantor/review team (non-commercial) institutions. Peer review There has been no peer review of this planned review yet. However, the results of this study are under consideration at Open Medicine.