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Role of Toll Like Receptor 4 (TLR-4) in lipolytic response mediated by acute exhaustive exercise

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Author(s):
Carolina Cabral Santos
Total Authors: 1
Document type: Doctoral Thesis
Press: Presidente Prudente. 2021-10-02.
Institution: Universidade Estadual Paulista (Unesp). Faculdade de Ciências e Tecnologia. Presidente Prudente
Defense date:
Advisor: Fabio Santos Lira; Jose Cesar Rosa Neto
Abstract

Role of Toll Like Receptor 4 in acute exhaustive exercise-mediated lipolytic response. The exhaustive exercise, carried out at moderate intensity, can affect elevations in free fatty acid concentrations, mainly mediated by the neuroendocrine response. Concomitant to this condition, it was postulated that endotoxemia favor the activation of the inflammatory response via Toll-Like Receptors (TLR), specifically TLR-4, in different cell types, favoring the production of cytokines such as interleukin 6 (IL-6) and Tumoral necrosis factor alpha (TNF-α). Additionally, it is speculated that the activation of TLR-4 during exhaustive exercise may favor the lipolysis process in adipose tissue thus increasing the availability of circulating fatty acids, however, this hypothesis has never been tested. In view of this, the objective of the present project will be to verify the relationship of TLR-4 and the process of lipolysis induced by the exhaustive exercise. To do this, the project will use two animal strains: C57BL/6J and TLR-4 knockout animal. For each animal lineage 4 subgroups will be formed, containing 8 animals in each one, namely: 1- sedentary control group (Rest); 2- exhaustive exercise group with euthanasia immediately after exercise (0h); 3- exhaustive exercise 2h after exercise (2h); 4- exhaustive exercise 6h after exercise (6h). The metabolic profile (glucose, lactate and free fatty acid concentrations) and inflammatory activity, as well as activity of lipolytic enzymes in the mesenteric and retroperitoneal adipose tissue, will be evaluated to determine the role of TLR-4. Saline group showed a decreased circulating free fatty acid concentration 6h after exercise (p=0.029; η2=0.136) that was not observed in the TLR-4 knockout group. The TLR-4 group showed high values in muscle-triacylglycerol content immediately after exercise (p=0.0001; η2=0.370), and that continuously decay until 6h (p=0.040; η2=0.142). Furthermore, the TLR-4 knockout group showed no increases in IL-10 levels after exercise when compared to Saline group (p=0.002) in the mesenteric deposit. In summary, our data demonstrate an important role of TLR-4 on substrate preferences. Furthermore, it was observed a possible participation of TLR-4 in the acute release role of the cytokines TNF-α and IL-10. (AU)

FAPESP's process: 15/26148-0 - Role of toll like receptor 4 (TLR-4) in lipolytic response mediated by acute exhaustive exercise
Grantee:Carolina Cabral Santos
Support Opportunities: Scholarships in Brazil - Doctorate