Muhidin Said O, Magan Ahmed A, Osman Khalid A, Syed Shareef, Ahmed Mohamed H
Department of Ophthalmology, Southampton University Hospitals, Southampton SO16 6YD, UK.
J Obes. 2012;2012:637538. doi: 10.1155/2012/637538. Epub 2012 Dec 10.
Nonalcoholic fatty liver disease (NAFLD) is closely related to insulin resistance, metabolic syndrome, obesity, type 2 diabetes, and dyslipidaemia. Obesity and metabolic syndrome are associated with an increased cancer risk, and recent evidence demonstrated an association between NAFLD and colorectal cancer (CRC). The mechanism of how NAFLD can be associated with increased risk of CRC is not fully understood; however, NAFLD represents a condition of profound insulin resistance and a proinflammatory state. Insulin and insulin-like growth factors may promote the development of CRC through their proliferative and antiapoptotic effects. Patients with NAFLD have reduced expression of adiponectin, an adipokine with anti-inflammatory effects. Importantly, hypoadiponectinemia is associated with an increased risk of CRC. Decreased levels of adiponectin lead to increased insulin levels due to marked insulin resistance and in turn increased insulin growth factor-1 (IGF-1). Insulin binds to IGF-1 receptors and plays an important role in cell proliferation, apoptosis, and increased production of vascular endothelial growth factor, an angiogenic factor that supports cancer growth. Further studies are needed to establish (i) the pathophysiology of NAFLD with colorectal cancer, (ii) the benefit of early screening of CRC in NAFLD patients, and (iii) the impact of treatment of NAFLD in the modulation of the risk of colorectal cancer.
非酒精性脂肪性肝病（NAFLD）与胰岛素抵抗、代谢综合征、肥胖、2型糖尿病和血脂异常密切相关。肥胖和代谢综合征与癌症风险增加有关，最近的证据表明NAFLD与结直肠癌（CRC）之间存在关联。NAFLD如何与CRC风险增加相关的机制尚未完全了解；然而，NAFLD代表一种严重胰岛素抵抗和促炎状态。胰岛素和胰岛素样生长因子可能通过其增殖和抗凋亡作用促进CRC的发展。NAFLD患者脂联素（一种具有抗炎作用的脂肪因子）的表达降低。重要的是，低脂联素血症与CRC风险增加有关。脂联素水平降低由于明显的胰岛素抵抗导致胰岛素水平升高，进而增加胰岛素生长因子-1（IGF-1）。胰岛素与IGF-1受体结合，在细胞增殖、凋亡以及增加血管内皮生长因子（一种支持癌症生长的血管生成因子）的产生中起重要作用。需要进一步研究以确定（i）NAFLD与结直肠癌的病理生理学，（ii）NAFLD患者早期筛查CRC的益处，以及（iii）NAFLD治疗对结直肠癌风险调节的影响。
