Ácidos biliares circulantes como marcadores tempranos de obesidad y salud cardiometabólica de adultos jóvenes

Laburpena

Obesity and cardiovascular diseases are the major causes of mortality in Western society. Circulating bile acids (BA) have emerged as modulators of obesity and cardiometabolic health since they are involved in the homeostasis of glucose, lipids and energy expenditure through several receptors such as the nuclear X-pharsenoid receptor (FXR) and Takeda G 5 protein coupled receptor (TGR5). However, the underlying mechanisms and the characterization of circulating BAs in the human metabolism remains poorly understood. The main aims of this doctoral thesis are i) to study whether there are differences between circulating levels of BA in men and women, and ii) to study the association of circulating levels of BA with markers of obesity and cardiometabolic health in young adults. Methods: Circulating BA, cardiovascular risk factors, body composition, as well as brown adipose tissue activation (BAT) were measured in a cohort of 136 young adults (45 men and 91 women). Results: Plasma levels of CDCA and GUDCA levels were higher in men than in women, although these differences disappeared after adjusting for fat mass. Plasma levels of CA, CDCA, DCA, and GDCA were positively, although weakly, associated with lean body mass, whereas plasma levels of GDCA and GLCA were negatively associated with 18F-fluorodeoxyglucose uptake (18F-FDG) by BAT. Interestingly, GCA, GCDCA and GUDCA were positively associated with serum levels of insulin, HOMA index, cholesterol levels and inflammation but were negatively associated with HDL-C and adiponectin, however, these correlations partially disappeared after adjusting for lean mass. Conclusions: The results of the present Doctoral Thesis show that the circulating levels of BA could be different between males and females, and could be considered early markers of the inflammatory and cardiometabolic health in young adults. In addition, this Doctoral Thesis highlights the role of lean mass, since the association between circulating BA levels and the cardiometabolic profile partially disappeared when adjusting for lean mass, however, further studies are needed to elucidate this new role.