Authors

• Ingrid Prkačin — University of Zagreb School of Medicine, Zagreb, Croatia — ORCID: 0000-0002-5830-7131

Abstract

In the last decade, we have witnessed a tendency of various medical professions to focus on an interdisciplinary approach, predominantly from the aspect of vascular health and based on advances in molecular physiology and genetics offering a translational approach not only in patient management but also for prevention of disease. The topical issue of obesity and the role of kidney in cardiovascular risk reduction have manifested through establishment of the Council on Kidney in Cardiovascular Disease at the American Heart Association to tackle the issue of obesity as part of translational medicine. Early recognition of the problem of obesity leads to reducing the sequels of not only kidney disease but also of the entire cardiovascular system, along with continuing treatment with interactive approach from pediatric through adult health care. It is crucial to change approach to the problem of obesity, especially because adipose cells are a hormonally active tissue secreting numerous cytokines that stimulate angiogenesis, thus causing systemic inflammatory event.

Keywords

KLJUČNE RIJEČI: pretilost, kardiovaskularni rizik, translacijska medicina, obesity, cardiovascular risk, translational medicine

DOI

Full Text

## Translational mechanisms Epigenetics has been depicted as an ever more relevant factor of disease onset in the development of kidney diseases and obesity, including close interplay of the gene expression regulation and phenotype effect on the existing gene structure (DNA) ( 12 ). The interaction of gene factors and environmental factors from the youngest age leads to predisposition to kidney disease, which can be related to the growing prevalence of prehypertension associated with obesity ( 12 ). Epigenetic alterations include DNA methylation and histone modification through the interplay of stable genome and variable environmental factors. The transforming growth factor beta (TGFβ) is the main mediator of accelerated aging, i.e. kidney fibrozation, which stimulates accumulation of extracellular matrix, thus interfering with normal kidney function. Elevated TGFβ level is found in the states of insulin resistance and obesity, while leptin is known to stimulate TGFβ proliferation in glomerular endothelial cells ( 13 ). Linking the interactions of all the factors mentioned above bears the potential of opening a new therapeutic site of acting to prevent development of not only kidney but also cardiologic diseases if mitochondrial structure and the mechanism of autophagy are properly stabilized. ## Measures that may reduce the problem of obesity The topical issue of obesity management in 2017 is best illustrated by the importance attached to this problem worldwide, as obesity is a disease of the 21 st century. Drugs used in the treatment of obesity include appetite suppressants, lipase inhibitors, and those acting on the renin-angiotensin-aldosterone system. However, most important is lifestyle modification with individually focused dietary regimen, psychological support and physical activity. Daily intake of only 16 grams of cereals (Dietary Guidelines for Americans, AHA, 2016) over a certain period has been demonstrated to reduce the mortality risk by 7 %, the risk of cardiovascular disease and related death by 9 %, and the risk of tumor death by 5 %. If the intake of cereals is increased to 48 grams daily, the risk of mortality can be decreased by 20 %, of cardiovascular disease by 25 % and tumor mortality by 14 %. These facts important for dietary habits and lifestyle can be explained by the dynamic interplay of genetics and epigenetics, which is related to the complex aging process ( 12 ). The most relevant characteristic of premature cell and tissue aging is reduced methylation (hypomethylation) due to restricted dietary intake of foods rich in methyl groups (folate, methionine, biotin, choline, and vitamins B2, B6 and B12). Deficient intake of diet high in methyl groups in childhood influences DNA methylation and increases the risk of unfavorable outcomes later in life, including development of malignant diseases, accelerated atherosclerosis, arterial hypertension, and obesity. Inadequate methylation is a characteristic of premature cell aging and obesity related diseases ( 13 ). ## Conclusion Understanding the interaction of external stimuli and epigenetic regulation of gene expression implies a completely new therapeutic reasoning on not only obesity related kidney disease and its genesis, but on the overall cardiovascular continuum. In the treatment of obese patients (not only hypertensive ones), the first choice should be drugs that inhibit the renin-angiotensin-aldosterone system and thus primarily decrease the intraglomerular pressure (podocyte lesion), while also reducing tissue fibrozation caused by aldosterone, as well as by additive immune mechanisms that reduce renal and vascular injury ( 14 , 15 ). Obesity is not just an aesthetic problem but also a serious public health issue that can considerably impair general health and quality of life. Education on the potential harmful consequences of obesity on the health of kidneys and the whole body from earliest childhood should be strongly promoted and healthy lifestyle that primarily involves exercise and physical activity advocated.