Adiponectina: relação com a distribuição de gordura corporal e influência sobre o risco de doenças cardiovasculares

Abstract

Adiponectin, a protein produced by mature adipocytes, has its concentration paradoxically reduced among obese individuals. Animal studies indicate that this protein has insulin-sensitizing, anti-inflammatory, and anti-atherogenic properties. However, the cardioprotective effect of adiponectin has not been clearly demonstrated in humans. To investigate the factors that modulate adiponectin concentration and the role of this protein in the etiology of cardiovascular diseases in humans is of great interest for a better understanding of the relationship between obesity and chronic diseases and for therapeutic purposes. This thesis aimed to evaluate the association of body fat distribution with blood adiponectin concentration and the effect of this protein on risk factors and on the incidence of cardiovascular disease in adults. The thesis includes three papers. In the first paper, we investigated the relationship between body fat distribution and adiponectinemia. For this, data from the 1982 Pelotas Birth Cohort and meta-data from two international genetic consortia (GIANT and ADIPOGen) were used. Our results indicate that adiponectin concentration decreases in obese individuals due to the expansion of central adipose tissue and not due to gluteofemoral fat accumulation. In the second paper, we explored the effect of circulating adiponectin concentration on the metabolic profile of over 10,000 individuals using the Mendelian randomization technique. This study included data from participants of 1982 Pelotas Birth Cohort, as well as participants from four other studies conducted in the UK (British Women Heart and Health Study, Whitehall II Study, The Caerphilly Prospective Study and The United Kingdom Collaborative Trial of Ovarian Cancer Screening nested case-control study). The results suggest that adiponectin does not directly promote a cardioprotective metabolic profile and that findings from conventional observational studies are likely to be explained by confounding due to factors such as obesity and insulin resistance. In the third paper, we evaluated the involvement of adiponectin in the etiology of cardiovascular disease, specifically coronary artery disease, using the Mendelian randomization technique with meta-data from six genetic consortia (CARDIoGRAM, CARDIoGRAMplusC4D, ADIPOGen, GIANT, MAGIC and GLGC) containing information from tens of thousands individuals. The results do not indicate that higher concentrations of adiponectin have the potential to reduce the risk of cardiovascular disease. In summary, findings from this thesis suggest that adiponectin production by fat tissue is modulated differently depending on tissue location and that blood adiponectin concentration does not appear to have a protective effect against cardiovascular disease in humans.