Metabolic syndrome (MS) is a cluster of metabolic disorders that collectively increase the risk of cardiovascular disease. Nitric oxide (NO) plays a crucial role in the pathogeneses of MS components and is involved in different mitochondrial signaling pathways that control respiration and apoptosis. The present review summarizes the recent information regarding the interrelations of mitochondria and NO in MS. Changes in the activities of different NO synthase isoforms lead to the formation of metabolic disorders and therefore are highlighted here. Reduced endothelial NOS activity and NO bioavailability, as the main factors underlying the endothelial dysfunction that occurs in MS, are discussed in this review in relation to mitochondrial dysfunction. We also focus on potential therapeutic strategies involving NO signaling pathways that can be used to treat patients with metabolic disorders associated with mitochondrial dysfunction. The article may help researchers develop new approaches for the diagnosis, prevention and treatment of MS.

Cardiovascular diseases remain the leading cause of death and disability. The development of cardiovascular diseases is traditionally associated with various risk factors, most of which are somehow related to an unhealthy lifestyle (smoking, obesity, lack of physical activity, etc.). There are also risk factors associated with genetic predisposition, as well as the presence of concomitant diseases, especially chronic ones. One of the most striking examples is, of course, type 2 diabetes. This metabolic disorder is associated with impaired carbohydrate metabolism. The main clinical manifestation of type 2 diabetes is elevated blood glucose levels. The link between diabetes and CVD is well known, so it is logical to assume that elevated glucose levels may be important, to some extent, in the context of heart and vascular disease. In this review, we tried to summarize data on the possible role of blood glucose as a risk factor for the development of CVD.

Interleukin (IL)-6 family cytokines act through a receptor complex with gp130 subunits. IL-6 is a pleiotropic cytokine that regulates inflammation and liver regeneration. Mitochondria are the first to respond to stress and adapt their dynamics in conditions of damage. In this regard, the study aimed to investigate the role of the IL-6 cytokine family (sIL-6Ra, gp130/sIL-6Rb, and IL-11) in the regulation of mitochondrial dynamics in the liver in obese patients and to assess the contribution of these cytokines to the pathogenesis of type 2 diabetes mellitus (T2DM). We studied 134 obese patients with and without T2DM and 41 healthy donors. We found that increasing the concentration of sIL-6Ra and gp130/sIL-6Rb protected against carbohydrate disorders in obese patients and prevented non-alcoholic fatty liver disease (NAFLD) progression in obese patients. An increase in plasma IL-6 levels is associated with decreased, mitochondrial transcription factor A (TFAM) protein production in liver biopsies in obese patients with and without T2DM. Replication, transcription, and division processes in liver biopsy were reduced in patients with T2DM. Inflammatory processes stimulate liver cell apoptosis in obese patients with T2DM. The increase in IL-11 levels is associated with decreased pro-apoptotic Bcl-2-associated X protein (BAX) protein production in obese patients with and without T2DM.

Atherosclerosis is one of the leading causes of mortality from cardiovascular disease (CVD) and is a chronic inflammatory disease of the middle and large arteries caused by a disruption of lipid metabolism. Noncoding RNA (ncRNA), including microRNA (miRNA), small interfering RNA (siRNA) and long noncoding RNA (lncRNA), was investigated for the treatment of atherosclerosis. Regulation of the expression of noncoding RNA targets the constituent element of the pathogenesis of atherosclerosis. Currently, miRNA therapy commonly employs miRNA antagonists and mimic compounds. In this review, attention is focused on approaches to correcting molecular disorders based on the genetic regulation of the transcription of key genes responsible for the development of atherosclerosis. Promising technologies were considered for the treatment of atherosclerosis, and examples are given for technologies that have been shown to be effective in clinical trials.

Metabolic syndrome (MetS) is a precursor to the major health diseases associated with high mortality in industrialized countries: cardiovascular disease and diabetes. An important component of the pathogenesis of the metabolic syndrome is mitochondrial dysfunction, which is associated with tissue hypoxia, disruption of mitochondrial integrity, increased production of reactive oxygen species, and a decrease in ATP, leading to a chronic inflammatory state that affects tissues and organ systems. The mitochondrial AAA + protease Lon (Lonp1) has a broad spectrum of activities. In addition to its classical function (degradation of misfolded or damaged proteins), enzymatic activity (proteolysis, chaperone activity, mitochondrial DNA (mtDNA)binding) has been demonstrated. At the same time, the spectrum of Lonp1 activity extends to the regulation of cellular processes inside mitochondria, as well as outside mitochondria (nuclear localization). This mitochondrial protease with enzymatic activity may be a promising molecular target for the development of targeted therapy for MetS and its components. The aim of this review is to elucidate the role of mtDNA in the pathogenesis of metabolic syndrome and its components as a key component of mitochondrial dysfunction and to describe the promising and little-studied AAA + LonP1 protease as a potential target in metabolic disorders.