my.chemie.de
With an accout for my.chemie.de you can always see everything at a glance – and you can configure your own website and individual newsletter.
Nature provides an enormous diversity of lipid molecules that originate from various pathways. Fatty acids are key modules for various lipids, including cell membrane lipids such as phospholipids or triacylglycerols, which are the major components of lipid droplets. Excess lipids or defects in lipid metabolism are associated with diseases such as metabolic syndrome.
Fig. 1 The endogenous fatty acid pool: Fatty acids (FA) are obtained either from endogenous synthesis or the diet. Gut microbiota are crucial for short chain fatty acid generation. FA can be further metabolized to complex lipids including phospholipids (PL) and triacylglyerols (TAG).
Lipids are either obtained from exogenous sources, i.e. diet, or from endogenous biosynthesis (Fig. 1). Numerous cellular processes such as cell growth or differentiation rely on de novo synthesis of fatty acids primarily for cell membrane generation [1]. The enzyme fatty acid synthase catalyzes the generation of palmitate (C 16:0) from acetate. Palmitate is a major saturated fatty acid in mammalian cells, tissue and plasma. It can be further metabolized by elongases and desaturases to longer chain and mono-unsaturated fatty acids. A crucial organ in overall lipid homeostasis is the liver, playing critical roles in many metabolic diseases, particularly in type 2 diabetes.
The key technology for lipid analysis is mass spectrometry. Because lipidomic approaches are nowadays able to cover almost the full lipidome, there is a real hype in the field as it opens new ways to study lipid biology in numerous research areas. However, this comes along with an increasing number of studies that report poor quality lipidomics data. The reasons for this are manifold covering analytical, bioinformatic and educational aspects. For instance, adequate controls of sample handling and processing to assure analyte stability are often missing, so are the use of appropriate internal standards, which are essential for proper quantification and identification of lipid species, and correct lipid annotation [2]. The application of stable isotope-labelled tracers combined with reliable mass spectrometric analysis is the state-of-the-art approach to gain insight into synthesis, metabolism and fluxes of lipid species [3].
The mammalian gut harbors highly complex microbial communities, referred to as the gut microbiota or microbiome when considering their genomes and surrounding environmental conditions. Previous studies have shown that the gut microbiota contributes to food processing; makes non-digestible nutrients available to the host; and provides important functions in host immunity, physiology and metabolism. As lipidomics, microbiome research is currently a hot topic in the scientific community and has even reached daily newspaper and broadcast media [4]. This contributed to the establishment of misleading concepts in the field that are mostly based on association studies [5].
The hype surrounding lipidomics and/or microbiome research led to a vast number of publications with diverse scientific quality. However, particularly in the last years, several studies have substantiated the importance of gut microbiota and lipids for principal biological processes, physiology and pathophysiology.
Fig. 2 The gut microbiota promotes hepatic fatty acid synthesis: Dietary fiber/polysaccharides is/are degraded and fermented to acetate in the gut lumen by gut microbiota. Acetate is used for synthesis of longer chain fatty acids and phospholipids after it reaches the liver via the portal vein [6].
We have just recently discovered an interaction between diet, gut microbiota and host lipid metabolism [6]. After employing multi-omics analyses, it was found that mice with gut microbiota have significantly elevated levels of mono-unsaturated fatty acids and expression of transcripts and proteins relevant for de novo lipid synthesis compared to mice without gut microbiota. Mono-unsaturated fatty acids are the final product of endogenous fatty acid generation. Using dietary intervention strategies and mechanistic investigations including stable isotope labelling in combination with mass spectrometry we demonstrated that hepatic lipid synthesis significantly depends on gut microbiota. The short chain fatty acid acetate originating from gut microbial degradation of dietary polysaccharides, i.e. fiber, by members of the phylum Bacteroidetes, is used as precursor for synthesis of longer chain fatty acids and phospholipids in the liver (Fig. 2).
Fig. 3 Stable isotope labeling of hepatic de novo fatty acid synthesis: Mice were supplemented with 13C-acetate via oral gavage (n=3/group) before palmitate of liver samples was analyzed for 13C-enrichment by gas chromatography coupled to mass spectrometry (GC-MS). Palmitate can be synthesized from labeled and/or unlabeled (natural) acetate monomers. The unlabeled monomers (grey) contain no 13C-isotopes, the labeled monomers (dark green) contain 13C. After four hours of labeling we found a significant enrichment of 13C in hepatic palmitate. The increased fractional abundances of M2-M6 isotopologues (comprising 13C) show that gut luminal acetate is a precursor for hepatic lipid synthesis.
To proof that acetate originating from the gut lumen is used for hepatic fatty acid de novo synthesis, mice were supplied with stable isotope-labeled (13C) acetate via oral gavage. The enrichment of 13C in palmitate from liver and plasma samples was confirmed after a mass spectrometric analysis (Fig. 3). To verify that hepatic lipid synthesis further depends on gut microbial acetate producers and dietary fiber, Bacteroidetes contents were modulated with antibiotics and mice were fed with diets containing a non-degradable and fermentable fiber source or different fiber contents.
Together, our work identified a novel lipid metabolic flux and synthesis pathway along the diet-gut microbiota-host axis.
To put the research fields on a reliable basis, experts have to join forces on a cross-border basis to define standards for robust microbiome research and lipid analyses. Further, scientists have to look beyond their horizon and critically evaluate the obtained data before publication to drive scientific progress in the fields. Our finding of gut microbiota influencing hepatic lipid synthesis might open the door to prevent and treat metabolic pathologies by specific modification of the diet and/or gut microbiota.
Josef Ecker`s research is supported by the “German Research Foundation” (DFG) [EC453/1-1; Priority Program (SPP) 1656, EC453/2-1; Collaborative Research Center – Project number 395357507 – CRC 1371] and “ZIEL – Institute for Food & Health”/Technical University of Munich (TUM).
___________________________________________________________________________________________
Category: Lipidomics | Metabolic Labeling
Literature:
[1] Ecker, J., Liebisch, G., Englmaier, M., Grandl, M., Robenek, H., Schmitz, G. (2010) Induction of fatty acid synthesis is a key requirement for phagocytic differentiation of human monocytes, Proc Natl Acad Sci USA, 107(17):7817-22, DOI: 10.1073/pnas.0912059107
[2] Liebisch, G., Ekroos, K., Hermansson, M., Ejsing, C.S. (2017) Reporting of lipidomics data should be standardized, Biochim Biophys Acta Mol Cell Biol Lipids, 1862(8):747-751, DOI: 10.1016/j.bbalip.2017.02.013
[3] Ecker, J., Liebisch, G. (2014) Application of stable isotopes to investigate the metabolism of fatty acids, glycerophospholipid and sphingolipid species, Prog Lipid Res 2014, 54:4-31, DOI: 10.1016/j.plipres.2014.01.002
[4] Hanage, W.P. (2014), Microbiology: Microbiome science needs a healthy dose of skepticism, Nature, 512(7514):247-8, DOI: 10.1038/512247a
[5] Clavel, T., Ecker, J. (2018) Microbiome and Diseases, Chapter 16, Book: The gut microbiome in health and disease (Editor: Dirk Haller), Springer International Publishing, ISBN 978-3-319-90544-0, DOI: 10.1007/978-3-319-90545-7
[6] Kindt, A., Liebisch, G., Clavel, T., Haller, D., Hörmannsperger, G., Yoon, H., Kolmeder, D., Sigruener, A., Krautbauer, S., Seeliger, C., Ganzha, A., Schweizer, S., Morisset, R., Strowig, T., Daniel, H., Helm, D., Küster, B., Krumsiek, J., Ecker, J. (2018) The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice, Nat Commun, 9(1):3760, DOI: 10.1038/s41467-018-05767-4
Molecular monitoring of RNA regulation
The better we understand cellular processes such as RNA regulation, the better molecular therapies can be developed. Until now, it has been especially difficult to track the regulation of non-coding RNA, which is RNA that is not further converted into proteins. A research team from the Tech ... more
Synthetic peptides may suppress formation of harmful deposits
In Alzheimer's disease, the degeneration of brain cells is linked to formation of toxic protein aggregates and deposits known as amyloid plaques. Similar processes play an important role also in type 2 diabetes. A research team under the lead of the Technical University of Munich has now de ... more
First electric nanomotor made from DNA material
A research team led by the Technical University of Munich (TUM) has succeeded for the first time in producing a molecular electric motor using the DNA origami method. The tiny machine made of genetic material self-assembles and converts electrical energy into kinetic energy. The new nanomot ... more
Vital wheat gluten, a protein with potential
For almost every one of the 17 goals that the 2030 Agenda for Sustainable Development sets out, food and its value chain plays an important role [1]. With this agenda, the United Nations has created a global framework for action that addresses all social players. more
Biobased raw material flows of the future
Anthropogenic climate change and the rising world population, in combination with increasing urbanization, poses global challenges to our societies that can only be solved by technological advancement. The direct biotechnological use of greenhouse gases, including residual biomass flows fro ... more
Taste and aroma boost in the mouth
The food trend towards healthy snacks is continuing. Snacks made from freeze-dried fruit meet consumer expectations of modern and high-quality food. However, freeze drying of whole fruits requires long drying times and substantially reduces sensorial quality, which is unappealing to consumers. more
Thomas Becker, born in 1965, studied Technology and Biotechnology of Food at the Technical University of Munich (TUM). He then worked as a project engineer at the company Geo-Konzept from 1992 to 1993. In 1995, he received his PhD from the TUM. From 1996 to 2004 he was Deputy Head of Depart ... more
Monika Wehrli, born in 1994, graduated from the ETH Zurich with a major in food process engineering. Since 2018 she has been working as a researcher at the Technical University of Munich, Germany, at the Chair of Brewing and Beverage Technology, where she pursues her doctorate in the field ... more
Thomas Brück, born in 1972, obtained his B.Sc. in chemistry, biochemistry and management science from Keele University, Stoke on Trent. Additionally, he holds an M.Sc. in molecular medicine from the same institution. In 2002, Thomas obtained his Ph.D. in Protein Biochemistry from Imperial C ... more
To make the most of your smallest quantities and ensure user safety, check out the tips and tricks in our guide "10 Steps to Successful Micro-Weighing" (…)
The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.
> more about q&more
q&more is supported by:
© 1997-2023 LUMITOS AG, All rights reserved
q&more articles
