Identificador: TDX:2506
Autors: Bosquet Agudo, Alba
Resum:
Adipose tissue, originally considered as simply a storage organ, has emerged as an endocrine organ that secretes fatty acids (FA) and adipokines. Plasma free FFA are usually elevated in obesity, contributing to the development of insulin resistance (IR) and cancer. In cells, FA are bound to FABPs (fatty acid binding protein), proteins that facilitate their transport to specific compartments in the cell. FABP4, expressed mainly in adipose tissue, has traditionally been implied to act as an intracellular lipid protein, but recently it has been detected in the circulation. However, the mechanism of action and functions of circulating FABP4 are poorly understood. The hypothesis of this study is that FABP4 acts as a transmitter of metabolic alterations related with obesity, such as skeletal muscle and hepatic IR. In these tissues FABP4 induces IR through the activation of endoplasmic reticulum (ER) stress. These peripheral transmission effects may also affect the growth of tumour processes, such as breast cancer, explaining the epidemiological relationship between obesity and neoplasia. We have demonstrated that FABP4 activates ER stress and attenuates the insulin signalling pathway in liver cells. Furthermore, FA and FABP4 exert a synergistic effect on the activation of ER stress. Pharmacological FABP4 inhibition by BMS309403 reduces saturated FA-induced ER stress and inflammation in skeletal muscle. Finally, FABP4 directly promotes the proliferation of breast cancer cells. Altogether, these results suggest that circulating FABP4 is not just a biomarker, since it may contribute to the development of diseases such as DT2 and cancer, as a result of interaction with peripheral tissue cells.
Repositori URV