Sick fat (adiposopathy) as the main contributor to metabolic syndrome

Abstract

Obesity, primarily the accumulation of visceral fat (prone to lipolysis and inflammation) is considered the most important pathogenetic link in insulin resistance, metabolic syndrome and type 2 diabetes mellitus. The purpose of the review was to present and summarize current information on the negative impact of adipose tissue dysfunction and the role of this phenomenon in the pathogenesis of the metabolic syndrome and type 2 diabetes mellitus. Material and methods. A systematic search of Web of Science, EMBASE, MEDLINE, and Google Scholar databases was performed. Results. Adipose tissue secretes a huge variety of biologically active substances - free fatty acids, adipokines, inflammatory mediators. These substances have a negative effect on insulin-sensitive and all other tissues, inducing inextricably linked freeradical oxidation, mitochondrial dysfunction, histotoxic hypoxia, maladaptive autophagy, apoptosis, dysregulation of transcriptome and post-translational processes, overload of non-fat tissues with lipids (lipotoxicity) enhanced by hyperinsulinemia, and many other cytotoxic mechanisms. Target organ damage disrupts the finely tuned network of feedbacks between the brain, liver, gut, microbiome, muscles, adipose tissue, classic glands and the rest of the organs, provided by myokines, hepatokines, bathokines and other substances, among others. Based on some experimental and clinical data, we agree with the notions that the qualitative aspect - adipocyte dysfunction (adiposopathy) - is at least as important as cell mass. Sick fat has a number of differences from healthy tissue, among which there are indicated mitochondrial dysfunction, inflammation, disorders of browning, cell death, and removal of senescent cells (senolysis). The obesity paradox can be explained from the pathophysiological point of view by this distinction (although the main explanation, in our opinion, should be sought in the internal validity of the works revealing this phenomenon). Conclusion. The treatment of obesity and its consequences should be based on «healing» rather than «extermination» of adipocytes. Implementation of this approach requires homeostatic influence on neuroimmunoendocrine regulation. Of the available tools, metformin, incretin drugs, sodium-glucose transporter inhibitors, and bariatric surgery probably meet this requirement the most.