The role of omega-3 in white and brown adipose tissue modulation and its function on the carcinogenic parameters of melanoma
Omega-3, Adipose tissue, Melanoma and Pyroptosis.
The n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) such as docosahexaenoic acid (DHA) have protective mechanisms against the establishment of inflammation diseases, such as obesity and cancer. DHA not only has important effects on adipose tissues, but also has the ability to induce pyroptosis cell death in some types of tumor cells. However, the role of n-3 PUFAS in the crosstalk between melanoma cancer and adipose tissue is poorly known. In this way, this work aimed to investigate the role of ômega-3 in adipose tissue modulation and its function on the carcinogenic parameters of melanoma, as well as the induction of pyroptosis. Mice (C57/BL6) were supplemented or not with omega-3 enriched in DHA at a concentration of 1g/kg for 30 days. After this period, serum, peritoneal lavage, adipose tissues, liver, and spleen were analyzed. In addition, secretion products of adipose tissues from these ômega-3 supplemented mice were isolated and used to stimulate melanoma cell line B16F10. Carcinogenic parameters such as cell viability, cell death, and cytokine quantification were evaluated. Moreover, MeWo cells were stimulated with DHA (12.5µM, 25µM, 50µM and 100µM) for 48h in vitro. Secretion of lactate dehydrogenase (LDH), caspase-1 activation and loss of plasma membrane integrity were analyzed. Our data demonstrated that supplementation with omega-3 enriched in DHA reduced the weight of adipose. Peritoneal lavage cells from supplemented animals had increased LD biogenesis but reduced reactive oxygen species (ROS) formation. In addition, the stimulation of B16F10 with the secretion products of brown adipose tissue (BAT) from supplement animals led to a decrease in cell viability as well as increased cell death and reduced IL-6 secretion by melanoma cells. Furthermore, the 25µM DHA concentration induced LDH release, increased Propidium Iodide uptake and induced caspase-1 activation, which are characteristic makers of cell death by pyroptosis. Thus, this study demonstrated the potential of omega-3 supplementation in modulating the profile and immune function of adipose tissues, as well as suggesting the ability of DHA to induce pyroptosis in melanoma cells in vitro. Therefore, generating new perspectives for the use of omega-3 as adjuvants in the treatment of melanoma.