DIFFERENCE IN FILOGENEZE ETIOLOGICAL FACTORS AND UNIVERSAL PATHOGENESIS OF METABOLIC PANDEMIAS. RELATIVE BIOLOGICAL "PERFECTION" AND INCONSISTENCY OF METABOLIC REGULATION IN VIVO
Regulation of metabolism in vivo can be better understood when phylogenesis of humoral, hormonal and vegetative regulatory factors is considered individually at the level of a) cells, b) paracrine regulated cell communities (PC), internal organs and their systems and c) the entire body. We suppose that each of these regulatory levels had formed at different stages of phylogenesis and terminated as "relative biological perfection" had been achieved. In our view, formation of internal organs and their systems also terminated at the level of this perfection. A systemic approach analysis of the three levels which were achieved consecutively in Homo sapiens has revealed regulatory discrepancies "visible through" relative biological perfection. We think that phylogenetic discrepancies in metabolic regulation at three levels of relative biological perfection are etiological factors of metabolic pandemias (diseases of civilization). All metabolic pandemias, including atherosclerosis, metabolic arterial hypertension, insulin resistance, obesity, metabolic syndrome, and nonalcoholic fatty liver disease are caused by a discrepancy in phylogenetically late biological function of locomotion. Etiological basis of metabolic (essential) arterial hypertension is laid by a regulatory discrepancy leading to local compensation of an impaired biological reaction metabolism <-> microcirculation in distal region of arterial bed involving endothelium-dependent vasodilation and systemic compensation at the entire organism level in proximal region of arterial bed. Two pools of phylogenetically separated fat cells (early visceral fat cells and late subcutaneous adipocytes) have been metabolically associated for millions of years. Insulin blocks hydrolysis of triglycerides and release of nonesterified fatty acids into circulation only in adipocytes but it cannot block lipolysis in phylogenetically early visceral fat cells and inhibit phylogenetically early hormones. An increase in plasma content of nonesterified fatty acids in the biological reaction of stress in vivo does not coincide with a proportional increase in albumin concentration. Function of phylogenetically early resident macrophages and monocytes <-> macrophages differentiated in arterial intima in situ and ex tempore is not the same. Adipocytes deposit fatty acids as nonpolar triglycerides in lipoproteins, while fatty acids are released in a polar nonesterified form.