Pereira Felipe V, Melo Amanda C L, Silva Marina B, de Melo Filipe M, Terra Fernanda F, Castro Iris A, Perandini Luiz A, Miyagi Marcelli T, Sato Fabio T, Origassa Clarice S T, Hiyane Meire I, Donato Jose, Wasinski Frederick, Araujo Ronaldo C, Festuccia William T L, da Silva Joao Santana, Camara Niels Olsen S
Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, São Paulo, Brazil.
Department of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina- Universidade Federal de São Paulo (EPM-UNIFESP), São Paulo, São Paulo, Brazil.
Nutr Cancer. 2021;73(4):642-651. doi: 10.1080/01635581.2020.1764982. Epub 2020 May 14.
There is a strong correlation between obesity and cancer. Here, we investigated the influence of IL-6 and gut microbiota of obese mice in melanoma development. We first evaluated B16F10 melanoma growth in preclinical models for obesity: mice deficient for leptin ) or adiponectin (AdpKO) and in wild-type mice (WT, C57BL/6J) fed a high-fat diet (HFD; 60% kcal from fat) for 12 weeks. The survival rates of and HFD-fed mice were lower than those of their respective controls. AdpKO mice also died earlier than WT control mice. We then verified the involvement of IL-6 signaling in obese mice that were inoculated with melanoma cells. Both and AdpKO mice had higher circulating IL-6 levels than wild-type mice. Melanoma tumor volumes in IL-6 KO mice fed an HFD were reduced compared to those of WT mice subjected to the same diet. Also evaluated the effect of microbiota in tumor development. Cohousing and fecal matter transfer experiments revealed that microbiota from mice can stimulate tumor development in lean WT mice. Taken together, our data show that in some conditions IL-6 and the gut microbiota are key mediators that link obesity and melanoma.
肥胖与癌症之间存在很强的相关性。在此，我们研究了肥胖小鼠的白细胞介素-6（IL-6）和肠道微生物群在黑色素瘤发展中的影响。我们首先在肥胖的临床前模型中评估了B16F10黑色素瘤的生长：瘦素缺乏小鼠（ ）或脂联素缺乏小鼠（AdpKO），以及喂食高脂饮食（HFD；60%千卡来自脂肪）12周的野生型小鼠（WT，C57BL/6J）。 小鼠和喂食HFD的小鼠的存活率低于各自的对照组。AdpKO小鼠也比野生型对照小鼠死亡更早。然后，我们验证了接种黑色素瘤细胞的肥胖小鼠中IL-6信号通路的参与情况。 小鼠和AdpKO小鼠的循环IL-6水平均高于野生型小鼠。与接受相同饮食的野生型小鼠相比，喂食HFD的IL-6基因敲除小鼠的黑色素瘤肿瘤体积减小。我们还评估了微生物群在肿瘤发展中的作用。同笼饲养和粪便转移实验表明， 小鼠的微生物群可以刺激瘦的野生型小鼠的肿瘤发展。综上所述，我们的数据表明，在某些情况下，IL-6和肠道微生物群是连接肥胖与黑色素瘤的关键介质。
