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脂肪貯蔵の秘密を明らかにする – 細胞がパーム脂肪をオリーブオイルに精製する


マウスの脂肪細胞内の脂肪滴: 滴の膜は緑色に染色され、その中に蓄えられた脂肪は赤色に染色されました。 クレジット: Johanna Spandl / ボン大学

この研究は、脂肪組織における重要なリモデリング プロセスの最初の正確な理解を提供します。

脂肪細胞はエネルギー貯蔵の手段として脂肪分子を利用します。 これらの分子は、グリセロール骨格に結合した 3 つの脂肪酸で構成され、一般にトリグリセリドと呼ばれます。 これらの分子は保存中に絶え間なく変化し、定期的に分解および再構築されると長い間信じられてきました。これは「トリグリセリド サイクリング」として知られるプロセスです。 しかし、この仮定は正しいのでしょうか? もしそうなら、このプロセスの目的は何ですか?

「今まで、これらの質問に対する本当の答えはありませんでした」と、ボン大学の LIMES 研究所のクリストフ ティーレ教授は説明します。 「過去 50 年間、この恒久的な再建の間接的な証拠があったことは事実です。 しかし、これについての直接的な証拠は今のところ不足しています。」

問題:トリグリセリドが分解され、脂肪酸が修飾されて新しい分子に再組み込まれることを証明するには、体内を移動する際の変換を追跡する必要があります. それでも、各細胞には何千もの異なる形態のトリグリセリドがあります. したがって、個々の脂肪酸を追跡することは非常に困難です。


「しかし、私たちは脂肪酸に特別なラベルを付けることを可能にする方法を開発しました。 彼の研究グループは、このようにさまざまな脂肪酸を標識し、それらを栄養培地に加えてマウスの脂肪細胞に加えました。 次にマウス細胞は、標識された分子をトリグリセリドに取り込んだ。

「私たちは、これらのトリグリセリドが変化しないままではなく、継続的に分解され、改造されていることを示すことができました。[{” attribute=””>acid is split off about twice a day and reattached to another fat molecule,” the researcher explains.

But why is that? After all, this conversion costs energy, which is released as waste heat – what does the cell get out of it? Until now, it was thought that the cell needed this process to balance energy storage and supply. Or perhaps it is simply a way for the body to generate heat.

“Our results now point to a completely different explanation,” Thiele explains. “It’s possible that in the course of this process, the fats are converted to what the body needs.”

Poorly utilizable fatty acids would consequently be refined into higher-quality variants and stored in this form until they are needed.

Fatty acids consist largely of carbon atoms, which hang one behind the other like the carriages of a train. Their length can be very different: Some consist of only ten carbon atoms, others of 16 or even more. In their study, the researchers produced three different fatty acids and labeled them. One of them was eleven, the second 16, and the third 18 carbon atoms long.

“These chain lengths are typically found in food as well,” Thiele explains.

Short fatty acids are eliminated, long ones “improved”

Labeling allowed the researchers to track exactly what happens to the fatty acids of different lengths in the cell. This showed that the fatty acids consisting of eleven carbon atoms were initially incorporated into triglycerides. After a short time, however, they were split off again and channeled out of the cell. After two days, they were no longer detectable. “Such shorter fatty acids are poorly usable by cells and can even damage them,” says Thiele, who is also a member of the Cluster of Excellence ImmunoSensation2. “Therefore, they are disposed of quickly.”

In contrast, the 16- and 18-atom fatty acids remained in the cell, although not in their original fat molecules. They were also gradually chemically modified, for example by additional carbon atoms being inserted. In the original fatty acids, the carbon atoms were moreover linked with single bonds – roughly like a human chain in which neighbors join hands. Over time, this sometimes developed into double bonds – as if revelers at a party were doing a conga. The fatty acids that are formed in this process are called unsaturated. They are better utilizable for the body.

“Overall, in this way the cells produce fatty acids that are more beneficial to the organism than those that we had originally supplied with the nutrient solution,” Thiele emphasizes. In the long term, this results for instance in the formation of oleic acid, a component of high-quality olive oil, from palmitate, such as that contained in palm fat. However, the cell cannot change the fatty acids as long as they are inside the fat molecule. They must first be split off, then modified, and finally tacked back on. Thiele: “Without triglyceride cycling, there is also no fatty acid modification.”

Adipose tissue can therefore improve triglycerides. If we eat and store food with unfavorable fatty acids, they do not have to be released in that state again when we are hungry. What we get back contains fewer “short” fatty acids, more oleic acid (instead of palmitate), and more of the important arachidonic acid (instead of linoleic acid). “Nevertheless, we should take care in our diet to consume high-quality dietary fats as much as possible,” the researcher stresses.

Because the refinement never works 100 percent. In addition, some of the fatty acids are not stored but used directly in the body. In the next step, the researchers now want to test whether the same processes occur in human adipose tissue as in individual mouse fat cells in the test tube. They also want to find out which enzymes make cycling work.

Reference: “Triglyceride cycling enables modification of stored fatty acids” by Klaus Wunderling, Jelena Zurkovic, Fabian Zink, Lars Kuerschner and Christoph Thiele, 3 April 2023, Nature Metabolism.
DOI: 10.1038/s42255-023-00769-z

The study was funded by the German Research Foundation (DFG).

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