Fatty acid metabolism plays a crucial role in various physiological processes, including energy production and signaling pathways. In intestinal inflammation studies, the analysis of fatty acid composition can provide valuable insights into the effects of dietary interventions on lipid metabolism and the associated inflammatory response.
In order to truly grasp the intricate nuances of these processes, it is necessary to harness the full potential of targeted lipidomics. A truly formidable instrument in the analytical toolkit, targeted lipidomics permits the precise measurement of hundreds of lipid species within a given biological sample. Utilizing targeted lipidomics, researchers are empowered to probe the ever-shifting landscape of fatty acid profiles, identifying those specific lipid species that are implicated in the pathogenesis of a given malady.
When taken as a whole, it becomes readily apparent that the study of fatty acid metabolism is a field replete with novel insights and discoveries, serving as an invaluable resource for the development of new therapeutic interventions and the elucidation of the mechanisms underpinning a panoply of diseases.
Case 1 Fatty acid analysis for intestinal inflammation study (1)
To determine the effect of dietary intervention on lipid composition, fatty acid content of liver and small intestine was examined by GC-MS. It was found that the ratio of arachidonic acid (AA) to docosahexaenoic acid (DHA) was three times higher in mice on a high n-6 diet compared to controls with the same total fatty acid content. In contrast, the ratio was significantly lower in mice on a high n-3 diet. This indicates that dietary modifications can indeed cause large changes in the relative composition of fatty acids. Also, LA, C18:2; C20:2; AA,C20:4 were significantly elevated in the high n-6 PUFA diet. And in the diet high in n-3 PUFA, α-LA,C18:3; EPA,C20:5; DHA,C22:6 class of fatty acids were significantly elevated. Clustering analysis was performed by LC-MS targeted metabolic methods to detect fatty metabolites and the pathways involved. Altered metabolites and associated inflammatory molecules were found.
This article finds altered metabolites and associated inflammatory molecules by establishing a model of local ischemia compared to changes in intestinal fatty acid classes in mice under different dietary conditions, using GC+LC targeting methods for fatty acid classes and arachidonic acid. The effects of dietary alterations on the inflammatory response in vivo and the modulatory effects were explained.
Case 2 Fatty acid analysis reveals the influence of gut microbiota on the process of defatting and elongation in the liver (2)
This study identified differences in the transcriptomics, proteomics, and phosphoproteomics of germ-free (GF) and specific pathogen-free (SPF) mice. The pathway significantly different between GF and SPF mice was lipid metabolism, as determined by multi-omics integration. Regression analysis of precursor and product fatty acids with enzymes and products of potential related pathways, combined with isotope labeling, revealed that acetate was a precursor of monounsaturated fatty acids. To further investigate the relationship between gut microbiota and lipid metabolism, various antibiotics were administered to SPF mice, and changes in the microbiota and the relationship between fatty acid desaturation/elongation were observed.
The study demonstrated that microbial colonization promotes liver fatty acid metabolism, as reflected in changes in the types of glycerophospholipids. Acetate produced by the degradation of dietary fiber by gut microbes is an important precursor for the synthesis of long-chain fatty acids in the liver. These colonization-driven host lipid metabolism changes may not only affect the biophysical membrane properties but also affect signaling processes, such as the production of prostaglandins, thereby affecting general physiology as well as inflammation and metabolic diseases.
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References
- Gobbetti, Thomas, et al. "Protective effects of n‐6 fatty acids‐enriched diet on intestinal ischaemia/reperfusion injury involve lipoxin A 4 and its receptor." British Journal of Pharmacology 172.3 (2015): 910-923.
- Kindt, Alida, et al. "The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice." Nature communications 9.1 (2018): 3760.