Obesity is a risk factor for malignant melanoma. The lungs are main target organs for metastization and their immune response is a key modulator of this mechanism. The concept that the metastatic potential of some types of cancer is reduced or inhibited by obesity, known as the obesity paradox, drives major concerns on the prognosis of metastasized patients. The aim of this study was to investigate how high-fat diet (HFD)-induced obesity affects melanoma metastization. C57Bl6/J mice were fed with HFD or standard diet for 180 days and inoculated intravenously with B16F10 melanoma cells. Upon 21 days of inoculation, lung tissue of overweight and lean mice was assessed for histology and immunohistochemistry assays. Adipokine antibody arrays were performed in mice serum. In vitro RAW 264.7 macrophage cultures were established and incubated with FGF-21 and/or lipopolysaccharide (LPS). Conditioned media was added to B16F10 cells for viability quantification. HFD-fed mice presented a reduced number of metastases with lower proliferative rates. The high content of inflammatory foci observed in noninoculated obese mice was significantly decreased upon B16F10 inoculation, concurrent with a slight fibrosis reduction. Plasma levels of fibroblast growth factor-21 (FGF-21), an endocrine regulator, were elevated in noninoculated HFD mice and the expression of FGF receptor 1 (FGFR-1) was significantly upregulated after inoculation. FGF-21 reduced melanoma viability in LPS-stimulated macrophages. Altogether, these findings suggest that higher amounts of FGF-21 are able to counterbalance the proinflammatory effects associated with obesity, protecting the lungs from melanoma metastization.

中文翻译：

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降低肥胖小鼠黑色素瘤肺转移负担：FGF-21 的作用。

肥胖是恶性黑色素瘤的危险因素。肺部是转移的主要靶器官，其免疫反应是该机制的关键调节剂。肥胖会降低或抑制某些类型癌症的转移潜力，即所谓的肥胖悖论，这一概念引起了人们对转移患者预后的主要关注。本研究的目的是调查高脂饮食（HFD）引起的肥胖如何影响黑色素瘤转移。C57Bl6/J 小鼠用 HFD 或标准饮食喂养 180 天，并静脉内接种 B16F10 黑色素瘤细胞。接种 21 天后，对超重和瘦小鼠的肺组织进行组织学和免疫组织化学分析评估。在小鼠血清中进行脂肪因子抗体阵列。建立体外 RAW 264.7 巨噬细胞培养物并与 FGF-21 和/或脂多糖 (LPS) 一起孵育。将条件培养基添加到 B16F10 细胞中以进行活力定量。高脂饮食喂养的小鼠的转移数量减少，增殖率降低。在未接种的肥胖小鼠中观察到的高含量炎症灶在接种 B16F10 后显着减少，同时纤维化略有减少。未接种的 HFD 小鼠中，内分泌调节剂成纤维细胞生长因子 21 (FGF-21) 的血浆水平升高，接种后 FGF 受体 1 (FGFR-1) 的表达显着上调。FGF-21 降低 LPS 刺激的巨噬细胞中黑色素瘤的活力。总而言之，这些研究结果表明，较高含量的 FGF-21 能够抵消与肥胖相关的促炎作用，保护肺部免受黑色素瘤转移。