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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/125025
The role of the G-protein coupled receptor 120 (GPR120) on the FGF21 system in white and brown adipose tissues
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[eng] Obesity prevalence has tripled in the last fifty years. For this reason, it is considered the pandemic of the century. It is characterized by the accumulation of metabolic abnormalities triggered by an increase in the size of fat depots in the body. Hence, new therapies to pursue an amelioration of metabolic abnormalities and adipose tissue dysfunction caused by this energy imbalance are being explored. The tissue responsible for the storage of fat is adipose tissue and it was considered just as an energy reservoir until recently. Currently, it is known to be actively involved in energy homeostasis at the same time that it fulfills endocrine functions. Adipose tissue is divided into two main types, white adipose tissue (WAT) and brown adipose tissue (BAT). While energy storage is the main role of WAT, BAT is able to dissipate energy in the form of heat leading to an increased energy expenditure. Surprisingly, it has been reported that WAT has the ability to recruit cells of the brown phenotype and thus increase its energy expenditure in a process denominated as browning. BAT activity and WAT browning are important components of energy expenditure and therefore potential therapeutic targets for the treatment of obesity and its comorbidities. In this work, we show that GPR120 activation, a membrane receptor for polyunsaturated fatty acids (PUFAs), promotes BAT thermogenic activity and WAT browning. The tissue that reported the highest levels of GPR120 expression is BAT, followed by colon and WAT different deposits. In addition, it was discovered that thermal stress (cold exposure) causes an induction in the expression of GPR120 in adipose depots. Likewise, the activation of GPR120 induces an increase in oxygen consumption. Conversely, mice deficient of GPR120 show decreased temperature and UCP1 expression in neonatal BAT and decreased browning after cold exposure in adult WAT. The administration of natural or synthetic agonists of GPR120, such as omega-3 PUFAs or GW9508, induced brown and beige adipocyte differentiation as well as their thermogenic activation and glucose oxidation. This activation by n-3 PUFAs was dependent of GPR120 expression. In addition to these findings, it was revealed that the activation of GPR120 induces the expression and release of fibroblast growth factor-21 (FGF21) by BAT and WAT at the same time that it increases plasma FGF21 levels. FGF21 is a hormonal factor able to induce thermogenic activation of BAT and browning of WAT, both associated with an improvement in metabolic conditions. In the absence of GPR120, the levels of FGF21 under cold stress conditions are decreased. Furthermore, n-3 PUFAs and synthetic agonists do not induce the expression and release of FGF21 in animals and cells deficient of GPR120. Regarding the effects on the activation of BAT, browning of WAT and the increase in glucose oxidation by the activation of GPR120, these are all compromised in mice or adipocytes lacking FGF21. Therefore, it is concluded that GPR120 activation induces BAT thermogenic activity and WAT browning through a mechanism that involves the induction of FGF21.
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QUESADA LÓPEZ, Tania paloma. The role of the G-protein coupled receptor 120 (GPR120) on the FGF21 system in white and brown adipose tissues. [consulta: 10 de desembre de 2025]. [Disponible a: https://hdl.handle.net/2445/125025]