PNAS：甲基乙二醛或导致体重增加和糖尿病

西奈山医学院的研究人员已经确定现代人的饮食中常见的化合物在腹型肥胖、胰岛素抵抗和2型糖尿病的发展中发挥重大作用。该研究结果发表在8月20日的PNAS杂志上。

Helen Vlassara医学博士带领下的研究小组发现，小鼠持续暴露于化合物甲基乙二醛（MG）下会显著出现腹部肥胖、早期胰岛素抵抗以及2型糖尿病症状。MG是一种晚期糖基化终产物（AGEs），主要是由食物干热煮熟时产生的。AGEs已经被证实会降低人体控制炎症的保​​护功能。

在这项研究中，一组老鼠连续四代喂食高MG的饮食，而对照组饲喂的饮食中没有MG。两组老鼠的饮食有正常的热量和脂肪。四代吃了MG的老鼠开始会出现早期胰岛素抵抗，体脂增加，而对照组则没有上述任何现象中的一个。研究人员发现MG会导致保护机制显著缺陷比如存在于脂肪中控制炎症同时增强葡萄糖和胰岛素代谢的生存因素SIRT1。MG的摄入对保护SIRT1和抵抗胰岛素的一种重要的抗-AGE受体AGER1也不利影响。

Vlassara博士说：这些关键的结果告知我们如何理解并防止人为肥胖和糖尿病的流行。这项研究表明，长期摄入看似无害的物质如MG会降低机体防御代谢等疾病的能力。

编译自：Specific toxic byproduct of heat-processed food may lead to increased body weight and diabetes

doi:10.1073/pnas.1205847109
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Oral advanced glycation endproducts (AGEs) promote insulin resistance and diabetes by depleting the antioxidant defenses AGE receptor-1 and sirtuin 1

Weijing Caia, Maya Ramdasa, Li Zhua, Xue Chena, Gary E. Strikera,b, and Helen Vlassaraa,b,1

The epidemics of insulin resistance (IR) and type 2 diabetes (T2D) affect the first world as well as less-developed countries, and now affect children as well. Persistently elevated oxidative stress and inflammation (OS/Infl) precede these polygenic conditions. A hallmark of contemporary lifestyle is a preference for thermally processed nutrients, replete with pro-OS/Infl advanced glycation endproducts (AGEs), which enhance appetite and cause overnutrition. We propose that chronic ingestion of oral AGEs promotes IR and T2D. The mechanism(s) involved in these findings were assessed in four generations of C57BL6 mice fed isocaloric diets with or without AGEs [synthetic methyl-glyoxal-derivatives (MG+)]. F3/MG+ mice manifested increased adiposity and premature IR, marked by severe deficiency of anti-AGE advanced glycation receptor 1 (AGER1) and of survival factor sirtuin 1 (SIRT1) in white adipose tissue (WAT), skeletal muscle, and liver. Impaired 2-deoxy-glucose uptake was associated with marked changes in insulin receptor (InsR), IRS-1, IRS-2, Akt activation, and a macrophage and adipocyte shift to a pro-OS/inflammatory (M1) phenotype. These features were absent in F3/MG? mice. MG stimulation of 3T3-L1 adipocytes led to suppressed AGER1 and SIRT1, and altered InsR, IRS-1, IRS-2 phosphorylation, and nuclear factor kappa-light chain enhancer of activated B cells (Nf-κB) p65 acetylation. Gene modulation revealed these effects to be coregulated by AGER1 and SIRT1. Thus, prolonged oral exposure to MG-AGEs can deplete host-defenses AGER1 and SIRT1, raise basal OS/Infl, and increase susceptibility to dysmetabolic IR. Because exposure to AGEs can be decreased, these insights provide an important framework for alleviating a major lifestyle-linked disease epidemic.