人变老是染色体终端缩短的结果。氧化应激和营养缺陷会加速这个过程。 ω－3多不饱和脂肪酸有两种，一种是DHA，另外一种是EPA。 澳大利亚的N.O.Callaghan和他的合作者研究结果证明，DHA可以明显减少染色体终端缩短的进程。这是首次把ω－3多不饱和脂肪酸与染色体缩短联系起来。 该研究结果发表在最新一期的Nutrition杂志。 论文的题目是 ： Telomere shortening in elderly people with mild cognitive impairment may be attenuated with omega-3 fatty acid supplementation: A randomised controlled pilot study 原文链接 http://www.sciencedirect.com/science/article/pii/S0899900713004450
来自日本学者 Iio A 等最近在《医学气体研究》杂志上发表论文，他们通过人类肝脏癌细胞的研究，提出氢气对脂肪代谢紊乱的作用和减少肝细胞上脂肪酸转运酶有关。该小组是氢气生物学效应研究的活跃小组，先后发表多篇文章。 http://www.ncbi.nlm.nih.gov/pubmed/?term=Ito+M%5BAuthor%5D+hydrogen%5Bti%5D 大量研究表明，肥胖的发生原因有三个方面的密切因素，脂肪酸代谢障碍、胰岛素抵抗和炎症。在肝脏脂肪变性发生过程中，肝细胞膜上的脂肪酸转运酶 CD36 介导的脂肪酸摄取过度是关键过程。最近研究发现，分子氢气具有减少脂肪变性、动脉硬化等患者和动物模型的氧化应激、促进脂类、糖和能量代谢，但具体分子机制大部分都不清楚。 本研究将肝癌 HepG2 细胞暴露在棕榈酸牛血清白蛋白复合体制备模型，使用或不使用氢气处理 24 小时。脂肪酸摄取采用荧光光谱测定法，脂肪酸含量采用油红染色检测。 JNK 磷酸化和 CD36 表达分别用 Western blot 和定量 PCR 检测。 结果发现，氢气预处理可减少棕榈酸诱导的细胞对脂肪酸的摄取，降低细胞脂质集聚，同时可以抑制 JNK 磷酸化激活（也检测了 P38 ，没有变化），虽然氢气不影响 CD36 的 mRNA 表达，但可以减少 CD36 蛋白的表达（这是什么原因值得追究）。 结果提示，氢气可以抑制肝脏细胞对脂肪酸的摄取，减少脂肪集聚，该效应是通过减少（ 50% 以上） CD36 蛋白表达，这一研究提供了一条探索氢气研究脂质代谢紊乱分子机制的途径。 本研究中最关键的是氢气处理细胞的方式：该试验是预处理方式，也就是说是在细胞受到损伤处理前用氢气处理 24 小时，那么氢气的效应主要作用在没有经过损伤的“正常”细胞上，出现一些变化才是后续效应的原因。对脂肪集聚是考察 24 小时，对分子变化是 120 分钟的快速效应，当然由于处理的氢气剂量非常高，达到 75% 浓度，时间比较长，达到 24 小时，要知道，由于氢气浓度处于爆炸浓度范围，除非采用高压，这种处理方式对动物和人体相对难以实现，因此这种效应如何和非常小剂量氢气关联是本研究无法回答的问题。 Briefly,cells were cultured in DMEM containing 0.67% (w/v) fatty acid-free BSA (Roche, Penzberg,Germany) under a humidified condition of 75% H2, 20% O2 and 5% CO2, or 95% air and 5% CO2 in a small aluminum bag. After treatment with or without hydrogen for 24 h, cells were treated with 0.67% fatty acid-free BSA or with 0.3 and 1.0 mM sodium palmitate (Sigma, St. Louis, MO, USA)-BSA complex (containing 0.67% fatty acid-free BSA) for 24 h to analyze the lipid content. Cells were also treated with fatty acid-free BSA or with 0.3 mM sodium palmitate-BSA complex for 120 min to analyze the protein phosphorylation. Med Gas Res. 2013 Mar 1;3(1):6. Molecular hydrogen attenuates fatty acid uptake and lipid accumulation through downregulating CD36 expression in HepG2 cells. fulltext 2045-9912-3-6.pdf Iio A, Ito M, Itoh T, Terazawa R, Fujita Y, Nozawa Y, Ohsawa I, Ohno K, Ito M. Abstract BACKGROUND: There is accumulating evidence that obesity is closely associated with an impaired free fatty acid metabolism as well as with insulin resistance and inflammation. Excessive fatty acid uptake mediated by fatty acid translocase CD36 plays an important role in hepatic steatosis. Molecular hydrogen has been shown to attenuate oxidative stress and improve lipid, glucose and energy metabolism in patients and animal models of hepatic steatosis and atherosclerosis, but the underlying molecular mechanisms remain largely unknown. METHODS: Human hepatoma HepG2 cells were exposed to palmitate-BSA complex after treatment with or without hydrogen for 24 h. The fatty acid uptake was measured by using spectrofluorometry and the lipid content was detected by Oil Red O staining. JNK phosphorylation and CD36 expression were analyzed by Western blot and real-time PCR analyses. RESULTS: Pretreatment with hydrogen reduced fatty acid uptake and lipid accumulation after palmitate overload in HepG2 cells, which was associated with inhibition of JNK activation. Hydrogen treatment did not alter CD36 mRNA expression but reduced CD36 protein expression. CONCLUSION: Hydrogen inhibits fatty acid uptake and lipid accumulation through the downregulation of CD36 at the protein level in hepatic cultured cells, providing insights into the molecular mechanism underlying the hydrogen effects in vivo on lipid metabolism disorders. 文献来源： http://www.medicalgasresearch.com/content/3/1/6/abstract
肿瘤细胞加大生产脂肪酸来推动其恶性增长。癌症研究人员想了解在这些细胞中脂肪酸的代谢与健康细胞中脂肪酸的代谢究竟有何不同,以便他们可以设计处理肿瘤细胞的目标，但并不是所有的脂肪酸都很容易研究。超长链（Very-long-chain）脂肪酸（其中含有C原子超过24个的脂肪酸）就是最难以捉摸的。但如今研究者已经开发出一种 13 C-方法来监控这些脂肪酸在细胞中的新陈代谢,通过液相色谱仪与高分辨质谱进行脂肪酸代谢分析，这对于癌症细胞生物学研究提供了一种新方法，原文详见： Liquid chromatography – high resolution mass spectrometry analysis of fatty acid metabolism Jurre J. Kamphorst , Jing Fan , Wenyun Lu , Eileen White , and Joshua D Rabinowitz Publication Date (Web): October 14, 2011 ( Article ) DOI: 10.1021/ac202220b October 26, 2011 Why The Long Fat? Cancer Biochemistry: Mass spectrometry follows the metabolism of very long fatty acids in cancer cells Erika Gebel Tumor cells ramp up the production of fatty acids to fuel their malignant growth. Cancer researchers want to understand the difference between fatty acid metabolism in these cells and that in healthy cells so that they can design treatments that target cancer cells. But not all fatty acids are easy to study. Very-long-chain fatty acids, those containing more than 24 carbons, are extremely rare and the most elusive. Now researchers have developed a method to monitor the metabolism of these fatty acids in cells, offering a new way to study cancer cell biology, the researchers say ( Anal. Chem., DOI: 10.1021/ac202220b). Fatty acid metabolism is complex: Cells use multiple tightly-regulated pathways to synthesize and break down dozens of types of fatty acids. “We don’t know how all these different pathways work together,”says Jurre Kamphorst of Princeton University , or how cancer genes change their regulation. It’s particularly difficult to monitor how long-chain fatty acids change in cancer, he says, because conventional analytical methods rely on bulk measurements that often miss the rare molecules. To determine where the elusive fatty acids come from and where they go, Kamphorst, Joshua D. Rabinowitz , and their colleagues developed a method that involves feeding cells 13 C-labeled glucose and glutamine, two molecules that flow into fatty acid synthesis pathways. Using mass spectrometry, the researchers could piece together the cells’ metabolic pathways by spotting where the 13 C landed in the cells’ fatty acid chains. The researchers first cultured mouse kidney cells with the labeled molecules. The scientists then extracted the cells’ fatty acids to analyze by liquid chromatography-mass spectrometry. They picked this technique because it keeps fatty acids intact. The scientists could detect 45 different fatty acids with between 14 and 36 carbons per chain, and at concentrations as low as 5 ng/mL. Fatty acids with the same length often had different 13 C labeling patterns, the researchers found. Based on these patterns and knowledge of metabolic pathways, Kamphorst and his team could figure out which fatty acids were made from scratch, which had been elongated in the cell, and which had been absorbed from the surrounding environment. To understand how fast-growing tumor cells satisfy their need for fatty acid production, the scientists also used their method to study mouse kidney cells expressing the gene ras, which promotes cancer cell growth. The researchers found that these cells had more long-chain fatty acids than did those without the gene, and that the cells produced this abundance by elongating fatty acids that they had absorbed from their surroundings. Benjamin Cravatt of the Scripps Research Institute , calls the new fatty acid analysis method “a good solution,” to a problem in the metabolism field. He points out that the researcher’s experiment in which they analyzed how cells with cancer genes make long-chain fatty acids “wouldn’t be possible if you didn’t have this method.” Jurre Kamphorst Lengthy Lipids Cells fed carbon-13-labeled molecules incorporate the carbon-13 (*) at any of various positions in their long chain fatty acids. Chemical Engineering News
一种特别的神经元触发一种控制身体饥饿反应的过程。一种涉及分解胞内组分的脂肪途径通过调节神经肽表达而控制摄食和体重。 当 资源 变得稀缺 ，我们 勒紧腰带 凑合度日 。 这也正 是 为 我们 的身体系统 ，当它 食物摄入量不足 的 情况 下 开始消耗 自身 。 在 细胞代谢 中 发表了一篇论文 ， 考希克 等 al.1 描述 如何 ， 当老鼠 被 剥夺 食物 ， 一个 专门 的 饥饿 敏感 神经元就把 身体储存中释放 的 脂肪当晚餐 。神奇的是 作者发现，只要干扰 神经元内的 这种信号途径，会养成更 精瘦 更轻佻 的 小鼠 ， 即使 食物 是自由供给的。 食物匮乏 和 饥饿 结果 导致 寻求食物和进食行为 。 内部 的 感官 系统检测到 能源短缺 的 信号 ， 在 血液 循环 ， 调节 神经回路并调节 这些行为 。 刺鼠肽 相关 蛋白 的基因 （ AGRP ） ，它编码 AGRP 神经肽 的 表达 ， 是 在这个系统中 一类关键的 神经元 。 AgRP 神经肽 注射 入脑 会 增加摄食 和 体重 。 此外 ， AgRP 表达神经元不出意料 有 一个 饥饿 传感系统 ：它们会 改变它 们 的放电频率 和 基因表达 ，以应答于 生长素 ，瘦素， 葡萄糖和脂肪酸 的 代谢 产物 信号 。 如果 没有 这些神经元 ， 小鼠 停止进食 2 相反 ， 精心喂养 的胖 老鼠亦 可 诱导出 贪婪的 饮食，只要 增加AgRP神经元 的 电活动 3 ， 4 。 因此，显然 ， AgRP 神经 功能 的 调节 控制 与饥饿有关的 行为 是很重要的 。 在 粮食匮乏 ， 在体内 发生变化 以 节约能源并产生 需要 进食 以补充 能量水平的信号 。 身体转换 为 使用 储存的脂肪作为燃料 ， 游离脂肪酸被 释放 到 血液中并可 由大脑 感受到 。 考希克 等 al.1 在 细胞培养 的小鼠AgRP 神经元中 研究 这一过程的 影响 。 下面的细胞内机制我不感兴趣： The authors explore an unusual mechanism for modulating Agrp gene expression by investigating the role of macroautophagy (here termed autophagy) in fatty-acid utilization. Autophagy is a regulated, cannibalistic process in which cells consume and recycle their components (such as damaged organelles) and use their internal structures as a fuel source during starvation. In autophagy, cellular components are enveloped in a membrane-bounded vesicle called an autophagosome for transport to an organelle known as the lysosome for degradation. Some of the authors of the current study previously discovered an intriguing mechanism in liver cells whereby the autophagy pathway can mobilize stored fat as a fuel source 5 . Kaushik et al . 1 report that a similar pathway operates in AgRP neurons, with consequences that seem to extend beyond fuel utilization. They propose that AgRP neurons accumulate free fatty acids from the blood during food deprivation and that these fatty acids are then quickly converted into triglyceride fats and stored in lipid droplets ( Fig. 1 ). These lipids are rapidly remobilized through autophagy of the lipid droplet, and free fatty acids are re-formed for use as fuel. The authors suggest that this circuitous pathway provides a mechanism for regulatory control over the accumulation of free fatty acids in the cell, so that they can be used in an orderly fashion. It remains to be seen whether this process operates in other neurons. 一种吞噬作用把脂肪酸吸收 表达 神经肽 AGRP的 神经元对 从 脂肪储存 释放的 循环 游离脂肪酸（ FFA）浓度 作出反应 ， 以及 其他 的 饥饿 信号 ， 如激素 的 浓度 和神经信号输入 。 Kaushiket al.1 显示 ， 这些不饱和脂肪酸 是 如何 采取 通过 脂肪酸 辅酶A 硫酯 （ FA - COA） 加工 成 甘油三酯 贮存 的脂滴 。 脂肪酸 可以 通过 自噬 途径 再次 被释放 ，其中 溶酶体 降解 的 脂滴 。 这些脂肪酸 增加 AGRP 基因 在细胞核 的 表达 ， 也 可 在线粒体中 代谢 A key finding from these experiments is that Agrp expression, which promotes eating, is increased by free fatty acids. In addition, this effect on gene expression requires lysosomal processing, as would be expected of the autophagy pathway. 扰乱 小鼠 的 脂质摄取会导致明显 后 果 。 利用 遗传敲 除 AGRP 神经元 细胞自噬 途径 的 一个 重要组分后 ， 作者 发现 ， 相对于 对照 组 ， 小鼠在 剥夺食物后再进食也吃得更少了， 体重也 下降了 。 他们后续研究揭示 ，这些小鼠的 AGRP 神经肽 表达下调了 ，他们认为这就是 为什么小 鼠 吃得更少 ， 重量更轻了。 These results 1 should be considered in the light of other studies demonstrating a role for fatty-acid metabolism in the regulation of Agrp expression. For example, Agrp expression is reduced when fatty-acid utilization is inhibited by eliminating an uncoupling protein involved in the activity of the mitochondrion, the cell's energy-producing organelle 6 . One implication is that the autophagy pathway could be linked to the transport of fatty acids for mitochondrial metabolism. Then there is the question of how cellular fatty acids regulate Agrp . One possibility for future investigation is the involvement of the transcription factor FoxO1, which regulates Agrp expression according to hunger status 7 . 我更关注这个： 目前尚不清楚 是否 中断 在 AGRP 神经细胞 自噬 途径 对 调节 摄食 和 体重 只通过 这里描述的 脂质 处理机制 。 所以必须探索这一途径中AGRP 神经元 的电活动，对它们的发育，以及它们与其他AGRP神经 功能的 调节子 ， 如 突触 的 输入和 激素调节 的 互动 ， which I been working on：） Could blocking this cannibalistic process be used to reduce body weight? Possibly, but the autophagy pathway is ubiquitous in cells throughout the body, so extensive investigation will be needed to find selective points of entry for therapeutic interference in obesity and eating disorders. ”这篇报道的核心就是FFA脂肪酸影响AgRP神经元活性，从而触发饥饿并诱导摄食“ 原文： Metabolism: Let them eat fat Scott M. Sternson Nature477 , 166–167(08 September 2011) 附件： 477166a.pdf
标签: 脂肪酸
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