| Summary: | Adipose tissue (AT) is considered a plastic and dynamic endocrine organ with
obesity driving changes in its biomechanical properties as well as in its extracellular matrix
(ECM) remodelling, inflammation and mechanotransduction profiles, leading to the
impairment of whole-body homeostasis. To achieve important and sustained weight loss
as well as for the resolution of obesity-associated diseases, bariatric surgery (BS) is
considered the most effective option in adequately selected patients. Despite great efforts
to understand the processes involved in both, the development of dysfunctional AT and the
favourable outcomes of BS, the underlying biological mechanisms have not been fully
disentangled. Therefore, the objective of the present PhD thesis is to evaluate changes in
AT plasticity together with their associations with the inflammation profile as well as ECM
remodelling and mechanotransduction properties in an animal model of diet-induced
obesity (DIO) and in patients with obesity. At the same time, we aimed to analyse the effect
of BS on these biological processes, beyond the mere weight loss. We found that changes
in the biomechanical properties of AT in obesity, including decreased Young’ modulus
(E), ultimate tensile strength (UTS) and strain at UTS, were associated with the
deterioration of body homeostasis. In this line, obesity induced changes in the
inflammation, fibrosis and ECM remodelling profiles not only in AT but also in the liver
being also related to the development of obesity comorbidities. Our findings also provide
new insights into AT adaptation after BS beyond caloric restriction, being demonstrated by
significant changes in the mechanotransduction and inflammatory profiles together with
the decrease in the crosslinking and synthesis of collagens as well as an increase in its
degradation. Our data also supports the notion that the higher blood vessel density found
in AT after BS is involved in the increased E, UTS and strain at UTS values, providing at
the same time higher stiffness and increased strain capacity. Furthermore, the inhibition of
NLRP3, a key component of the inflammasome involved in the regulation of inflammation,
in visceral adipocytes significantly blocked inflammation and fibrosis suggesting its
potential to regulate the development of obesity-associated comorbidities. In terms of
fibrosis-inducing factors, we also showed a novel role of dermatopontin in the pathological
AT ECM remodelling during obesity. Finally, we proposed that the measurement of the
Adiponectin/Leptin ratio after BS might constitute a significant factor for evaluating the
remission of type 2 diabetes after bariatric procedures.
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