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. [Epub ahead of print]

Molecular hydrogen attenuates fatty acid uptake and lipid accumulation through downregulating CD36 expression in HepG2 cells.

fulltext

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