Mitochondrial Dysfunction is to Blame for Obesity

IKBFU scientists analysed the studies on the relationship between intracellular processes in mitochondria and metabolic disorders in the human body, which lead to obesity and cardiovascular diseases. The review was supported by the Russian Science Foundation and published in the International Journal of Molecular Sciences.

Obesity is the main factor in the development of metabolic syndrome (MetS), which is characterised by complications such as hypertension and high cholesterol. MetS is also a precursor of major health diseases associated with high mortality in industrialised countries: cardiovascular disease and diabetes.

The World Health Organization estimates that the global incidence rate of metabolic syndrome in adults is over 25% and increasing every year. This increases the risk of developing type 2 diabetes (fivefold), having a heart attack (threefold), and dying (twofold).

Mitochondrial dysfunction, i.e. improperly functioning "power houses" of the cell, is a significant factor in the development and progression of diseases linked to metabolic syndrome (MetS). Specifically, issues related to the mitochondrial genome (mtDNA) have been identified as causing health problems.

Despite the growing body of evidence and research on MetS and its connection to mitochondrial dysfunction, there are still many important questions that have not been explored and require more in-depth analysis.

How are mitochondria connected with it? Within each cell, there are numerous mitochondria, which are responsible for cell respiration and the production of ATP, a molecule essential for the functioning of all living organisms.

Interestingly, mitochondria have their own genome (mtDNA), which is distinct from the regular human DNA.This difference is a result of the mitochondria having evolved from a bacterium. The state of the organism affects the integrity of mitochondria and their genetic information. For instance, when inflammation occurs in adipose tissue, mtDNA starts to deteriorate as specialised cells attempt to control the inflammatory process. This leads to insulin resistance and subsequently disrupts mitochondrial integrity.

Notably, those with heart disease are more likely to be deficient in mtDNA, which impairs the optimal functioning of mitochondria and leads to reduced energy supply for the heart. Conducting additional research involving larger populations from diverse countries will provide a more accurate understanding of the molecular genetic connections between mtDNA alterations and metabolic syndrome disorders, thus filling the existing gaps in knowledge about the development of the disease. Simultaneously, studying the potential for cell repair, especially in relation to mitochondria, will help develop a system for diagnosing metabolic disorders and identify targeted molecules for pathogenetically based treatment.

Natalia Todosenko, researcher at the IKBFU Centre for Immunology and Cell Biotechnology

Mitochondria are unique organelles containing their own genome, known as mitochondrial DNA (mtDNA), which is separate from the human genome.Low levels of mtDNA, often observed in obesity, can result in reduced mitochondrial respiratory capacity, inflammation, cellular and tissue ageing, and the development of conditions like insulin resistance, type 2 diabetes, cardiovascular diseases, and metabolic syndrome (MetS). Certain cell enzymes may have the ability to restore mitochondrial function and safeguard mtDNA. These enzymes hold potential for the development of new medications targeting diseases linked to metabolic syndrome.