Use for Triglyceride-Cycling in adipose tissue revealed
For more than 50 years, it has been suspected that adipocytes permanently remodel the lipids stored in them. ImmunoSensation2 member Christoph Thiele and his team at the University of Bonn have now for the first time demonstrated this process in cell culture. The study shows that the cells are able to quickly eliminate harmful fatty acids or alternatively refine them into more usable molecules. The results have now been published in the journal Nature Metabolism.
Fat molecules serve fat cells as energy stores. They consist of three fatty acids attached to a framework of glycerol. They are therefore also called triglycerides. It has long been suspected that these molecules do not remain unchanged during their storage period. Instead, they are regularly broken down and reassembled - a process called "triglyceride cycling." But is this assumption even true? And if so, what would be the point? "Until now, there has been no real answer to these questions," explains Prof. Dr. Christoph Thiele of the LIMES Institute at the University of Bonn. "It is true that there has been indirect evidence of this permanent reconstruction for 50 years. But direct proof of it has been lacking until now."
The problem: To prove that fatty acids are split off, modified and reincorporated into new molecules, one would have to track their transformation as they travel through the body. But there are hundreds of thousands of triglycerides in every cell. Keeping track of individual fatty acids is therefore extremely difficult.
Label makes fatty acids unmistakable
"We have developed a method that allows us to attach a special label to fatty acids, making them unmistakable," says Thiele. His research group labeled various fatty acids in this way, added them to nutrient medium and administered them to cultured murine adipocytes. The mouse cells then incorporated the labeled molecules into triglycerides. "We were able to show that these triglycerides do not remain unchanged, but are continuously degraded and remodeled: Each fatty acid is cleaved about twice a day and reattached to another fat molecule," the scientist explains.
But why is this so? 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 store and supply energy. Or perhaps it is a simple way for the body to generate heat. "Our results now point to a completely different direction," Thiele explains. "It's possible that the fats are reworked in the course of this process in the way the body needs them." Poorly utilizable fatty acids would thus be refined into higher-quality variants and stored in this form until they are needed.
In their study, the researchers produced three different labeled fatty acids. One of them was eleven (C11), the second 16 (C16) and the third 18 carbon (C18) atoms long. "These chain lengths are typically also found in food," Thiele explains.
Short fatty acids are eliminated, long ones refine
By labeling them, the researchers were able to track exactly what happens to the fatty acids of different lengths in the cell. This showed that the C11 fatty acid initially incorporated into triglycerides. After a short time, however, it was split off again and discharged from the cell. After two days, it was no longer detectable. "Such shorter fatty acids are poorly usable by cells and can even damage them," says Thiele. "Therefore, they are quickly discarded."
In contrast, the C16 and C18 fatty acids remained in the cell, albeit not in their original fat molecules. They also gradually underwent chemical changes, such as the insertion of more carbon atoms and the formation of double bonds, generating unsaturated fatty acids, more valuable to the body.
"Overall, the cells produce fatty acids in this way that are more favorable for the organism than those that we originally supplied with the nutrient solution," Thiele emphasizes. In the long term, for example, palmitate, such as that contained in palm fat, is turned into oleic acid, a component of high-quality olive oil. However, the cell cannot change the fatty acids as long as they remain in the fat molecule. They must first be cleaved off, then modified and finally reattached. Thiele: "Without triglyceride cycling, there is also no fatty acid modification."
Fat tissue can therefore improve triglycerides. When we eat and store unfavorable fatty acids, they don't have to be released in the same form when we starve. 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 eat the highest-quality edible fats possible," the scientist emphasizes. Because the refinement never works 100 percent. In addition, some of the fatty acids are not stored, but are used directly in the body. In the next step, the researchers now want to check whether the same processes take place in human fat tissue as in individual mouse fat cells in the test tube. They also want to find out which enzymes keep cycling going.
Funding
The study was funded by the German Research Foundation (DFG).
Publication
Klaus Wunderling, Jelena Zurkovic, Fabian Zink, Lars Kuerschner & Christoph Thiele: Triglyceride cycling enables modification of stored fatty acids, Nature Metabolism, DOI: doi.org/10.1038/s42255-023-00769-z
Contact
LIMES Institute (Life & Medical Sciences) of the University of Bonn
Tel. +49 228 736 2818
E-mail: cthiele@uni-bonn.de
