Obesity has been declared the largest global chronic health problem in adults by World Health Organization, considering all the associated cardiovascular, orthopedic, reproductive and metabolic complications. It is nowadays clear that visceral adipose tissue accumulation is strictly related to metabolic complications. In recent years, new evidences in mouse models demonstrated that the correct expansion of adipose tissue is able to prevent metabolic complication even in obese animals. The main characteristics of this "healthy" adipose tissue accumulation are smaller and more abundant adipocytes, high blood vessels density, low fibrosis and high adiponectin synthesis. Studies on mouse models demonstrated that adipocyte precursor could differentiate into functional white adipocytes or into fibrogenic progenitors, not able to differentiate in mature adipocytes. Fibrogenic progenitors express collagen and PDGFRb, inducing fibrosis, produce inflammatory cytokines and promote macrophage infiltration and activation. The importance of increased fibrosis at the expend of functional adipogenesis in human white adipose tissue dysfunctional expansion has not been completely clarified.
The aim of this study is to evaluate, through real time PCR, the expression of a panel of genes involved in adipogenesis, lipid function and storage trough the synthesis of triglycerides and adipokines, inflammatory pathway and fibrogenesis in human visceral and subcutaneous adipose tissue specimens, already collected in the context of Chiasm study, comparing metabolically healthy obese and morbid obese patients.
Animal studies have demonstrated the great importance of correct adipose tissue expansion in response to high fat diet for avoiding metabolic diseases. The ability to maintain a healthy adipose tissue, characterized by small and abundant adipocytes, high blood vessels density (no hypoxia) and low fibrosis, determines a metabolically healthy phenotypes, even in the presence of obesity.
The confirmation of the role of correct white adipose tissue expansion in human obesity and metabolic complications could help characterizing the processes at the base of adipose tissue dysfunctions. In fact, the amount of adipose tissue is only one factor in the developing of metabolic complications due to obesity, as testified by the high percentage of metabolically healthy obese patients and, on the other hand, by normal weight patients affected by metabolic complications.
The evaluation of the contemporary expression of inflammatory mediators and fibrogenic factors and of a panel of genes involved in adipocytes differentiation and functioning in human visceral and subcutaneous adipose tissue, both in metabolically healthy obese and morbid obese patients, will help clarifying the role of fibrosis and adipocytes disfunction in metabolic complications. In particular, it will be tested even in humans if, in case of obesity-dependent metabolic complications, there is an increased expression in genes linked to fibrosis at the expend of pre-adipocytes differentiation and functioning.
These findings will open the way to the discover of possible factors or pathway to be targeted by new treatments for allowing healthy adipose tissue expansion in humans, reducing cardiovascular and metabolic complications.