Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
Curr Opin Lipidol. 2013 Feb;24(1):4-11. doi: 10.1097/MOL.0b013e32835aea13.
To highlight the potential importance of advanced glycation endproducts (AGEs) and advanced-lipoxidation endproducts (ALEs) in obesity and obesity-related complications, and the contribution of the receptor for advanced glycation endproducts (RAGE) and the glyoxylase defense system therein.
Formation of AGEs/ALEs and its precursors, including methylglyoxal (MGO), are increased in conditions characterized by hyperglycemia, hyperlipidemia and enhanced oxidative stress. This metabolic profile is generally considered typical for obesity. Increased plasma and/or tissue levels of MGO and of specific AGEs/ALEs, such as N(ε)-(carboxymethyl)lysine (CML), in obesity have recently been described. In addition to increased formation, the suppressed defense system in obesity against AGEs/ALEs formation, that is, the glyoxylase system, will further contribute to AGEs/ALEs formation in obesity. AGEs/ALEs are not inert. In-vitro studies showed that AGEs induced the production of inflammatory mediators in adipocytes and macrophages via RAGE activation, which may subsequently contribute to the development of obesity-related complications.
The recognition of an enhanced AGEs/ALEs formation in adipose tissue and the biological consequences thereof may lead to a further understanding of underlying mechanisms in dysregulated production of adipokines in obesity.
综述目的：强调晚期糖基化终末产物 (AGEs) 和晚期脂质氧化终末产物 (ALEs) 在肥胖及肥胖相关并发症中的潜在重要性，以及糖基化终末产物受体 (RAGE) 和其中的糖基化酶防御系统的作用。
最新发现：在高血糖、高血脂和氧化应激增强的情况下，AGEs/ALEs 及其前体（包括甲基乙二醛 (MGO)）的形成增加。这种代谢特征通常被认为是肥胖的典型特征。最近描述了肥胖症中 MGO 和特定 AGEs/ALEs（如 N(ε)-(羧甲基)赖氨酸 (CML)）的血浆和/或组织水平升高。除了形成增加外，肥胖症中针对 AGEs/ALEs 形成的防御系统（即糖基化酶系统）受到抑制，这将进一步促进肥胖症中 AGEs/ALEs 的形成。AGEs/ALEs 并非惰性物质。体外研究表明，AGEs 通过 RAGE 激活诱导脂肪细胞和巨噬细胞中炎症介质的产生，这可能随后导致肥胖相关并发症的发展。
总结：认识到脂肪组织中 AGEs/ALEs 形成的增加及其生物学后果，可能会进一步了解肥胖症中脂联素产生失调的潜在机制。
