In 2016, the Nobel Physiology Prize winner was Yoshinori Ohsumi, a researcher, for discovering the mechanism of autophagy and the genes regulating the substantial physiologic functions of degradation and recycling of cellular components induced by different ways of cell damage (e.g., infection or stress) (1). The mechanism of autophagy is of utmost importance in reducing negative consequences of aging on a daily basis, and is relevant for cell differentiation (2). Inappropriate mechanism of autophagy has been associated with a variety of diseases such as Parkinson’s disease, diabetes mellitus type 2, tumor disease development, and many other disorders related to premature aging (3). The potential mechanisms influencing cellular lipid metabolism have been described in experimental researches, indicating that decreased lipid accumulation results in lower glomerular injury (4). It is quite understandable that modern medicine tends to develop drugs with a potential to influence the mechanism of autophagy and reduction of ectopic adipose tissue accumulation, thus resuming balance at the cellular level, i.e. at the lysosomal and mitochondrial level (5).

Although this all may seem quite simple at the first sight, obesity is a much more complex issue because obesity is a state of chronic inflammatory response (6). The leptin and adiponectin imbalance is the main factor associated with insulin resistance, cardiovascular disease, and glomerular injury. Leptin receptor is found predominantly in renal medulla and belongs to the family of class I cytokine receptors associated with inflammatory response in obesity. Visceral adipose tissue produces large amounts of interleukin-6, supporting the comprehensive theory on obesity as a state of systemic inflammatory response (7).

Other features of obesity include hypoadiponectinemia, hyperleptinemia and hyperaldosteronism. Hypoadiponectinemia is regulated by the level of fetuin-A, a glycoprotein synthesized in the liver and associated with development of insulin resistance, cardiovascular disease and glomerular injury. Hyperleptinemia increases tubular salt reabsorption, whereas hyperaldosteronism exerts dual action, either by inducing glomerular hyperfiltration (similar to leptin action) or by direct podocyte injury due to the formation of nitrogen reactive species. Another potential kidney (not exclusively) vascular damage implies that obesity is characterized by increased calorie intake along with a decreased level of adiponectin, which reduces the activity of ‘energy sensor’ (5’AMP activated protein kinase) found in hepatocytes and podocytes, thus causing albuminuria.

Furthermore, the impairments related to obesity are characterized by the mechanism of insulin resistance that is pronounced in diabetes mellitus type 2, aging and lipodystrophy, and by ectopic fat accumulation that contributes to organ damage in metabolic diseases. Such a scenario suggests that the obesity related kidney disease might be considered as a state of lipodystrophy, i.e. systemic storage disorder (8). It is characterized by loss of ‘white’ adipose tissue and dyslipidemia, along with the mentioned lipid accumulation at ectopic sites (8). This ectopic fat storage in the kidney is accompanied by increased oxidative stress, which together result in premature aging (9). The effect of increased oxidative stress on adipose tissue occurs due to the reduced level of glutathione, which inhibits pre-adipocyte differentiation. The pathogenic role in enhanced oxidative stress is played by asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS). ADMA is degraded by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). Adipocytes have been demonstrated to produce ADMA and DDAH type 1 and 2, resulting not only in adipose tissue accumulation but also in impaired maturation (6).

Imbalance is the basic impairment. This mechanism of imbalance between body weight and body composition has been recognized as a state of increased inflammatory state of the body, which also influences telomeres. Considering telomeres, it should be noted that telomeres are specific DNA-protein structures at the end of the eukaryotic chromosomes and are markers of biologic aging. The aging process is accelerated by telomere damage (10). Short telomeres have been demonstrated to be associated with elevated body mass index, proneness to obesity, increased waist-to-hip ratio, and increased level of visceral fat. Indeed, many metabolic components of obesity cause dysfunction of the kidney (and other organs) due to accelerated aging process (10).

Accordingly, it should be emphasized that the synergistic action of impaired lipid metabolism, insulin resistance and inflammatory process activation leads to development of glomerulopathy associated with obesity, as well as to renal and cardiovascular diseases, these all being underlain by the mechanism of autophagy (11).