Search Results (19)

Atopic dermatitis (AD) is a common inflammatory skin disease, in particular among infants, and is characterized, among other things, by a modification in fatty acid and ceramide composition of the skin’s stratum corneum. Palmitic acid and stearic acid, along with C₁₆-ceramide and 2-hydroxy C₁₆-ceramide, occur strikingly in AD. They coincide with a simultaneous decrease in very long-chain ceramides and ultra-long-chain ceramides, which form the outermost lipid barrier. Ceramides originate from cellular sphingolipid/ceramide metabolism, comprising a well-orchestrated network of enzymes involving various ELOVLs and CerSs in the de novo ceramide synthesis and neutral and acid CERase in degradation. Contrasting changes in long-chain ceramides and very long-chain ceramides in AD can be more clearly explained by the compartmentalization of ceramide synthesis. According to our hypothesis, the origin of increased C₁₆-ceramide and 2-hydroxy C₁₆-ceramide is located in the lysosome. Conversely, the decreased ultra-long-chain and very long-chain ceramides are the result of impaired ELOVL fatty acid elongation. The suggested model’s key elements include the lysosomal aCERase, which has pH-dependent long-chain C₁₆-ceramide synthase activity (revaCERase); the NADPH-activated step-in enzyme ELOVL6 for fatty acid elongation; and the coincidence of impaired ELOVL fatty acid elongation and an elevated lysosomal pH, which is considered to be the trigger for the altered ceramide biosynthesis in the lysosome. To maintain the ELOVL6 fatty acid elongation and the supply of NADPH and ATP to the cell, the polyunsaturated PPARG activator linoleic acid is considered to be one of the most suitable compounds. In the event that the increase in lysosomal pH is triggered by lysosomotropic compounds, compounds that disrupt the transmembrane proton gradient or force the breakdown of lysosomal proton pumps, non-HLA-classified AGEP may result. Full article

Lipids are a large group of natural compounds, together with proteins and carbohydrates, and are essential for various processes in the body. After death, the organism’s tissues undergo a series of reactions that generate changes in some molecules, including lipids. This means that determining the lipid change profile can be beneficial in estimating the postmortem interval (PMI). These changes can also help determine burial sites and advance the localization of graves. The aim was to explore and analyze the decomposition process of corpses, focusing on the transformation of lipids, especially triglycerides (TGs) and fatty acids (FAs), and the possible application of these compounds as markers to estimate PMI and detect burial sites. A systematic review of 24 scientific articles from the last 23 years (2000–2023) was conducted. The results show that membrane glycerophospholipids (such as phosphatidylcholine and phosphatidylglycerol, among others) are the most studied, and the most promising results are obtained, with decreasing patterns as PMI varies. Fatty acids (FAs) are also identified as potential biomarkers owing to the variations in their postmortem concentration. An increase in saturated fatty acids (SFAs), such as stearic acid and palmitic acid, and a decrease in unsaturated fatty acids (UFAs), such as oleic acid and linoleic acid, were observed. The importance of intrinsic and extrinsic factors in decomposition is also observed. Finally, as for the burial sites, the presence of fatty acids and some sterols in burial areas of animal and human remains can be verified. In conclusion, glycerophospholipids and fatty acids are good markers for estimating PMI. It has been observed that there are still no equations for estimating the PMI that can be applied to forensic practice, as intrinsic and extrinsic factors are seen to play a vital role in the decomposition process. As for determining burial sites, the importance of soil and textile samples has been demonstrated, showing a direct relationship between saturated fatty acids, hydroxy fatty acids, and some sterols with decomposing remains. Full article

Lipid reprogramming metabolism is crucial for supporting tumor growth in breast cancer and investigating potential tumor biomarkers. Fatty acid esters of hydroxy fatty acids (FAHFAs) are a class of endogenous lipid metabolites with anti-diabetic and anti-inflammatory properties that have been discovered in recent years. Our previous targeted analysis of sera from breast cancer patients revealed a significant down-regulation of several FAHFAs. In this study, we aimed to further explore the relationship between FAHFAs and breast cancer by employing chemical isotope labeling combined with liquid chromatography−mass spectrometry (CIL-LC-MS) for profiling of FAHFAs in tumors and adjacent normal tissues from breast cancer patients. Statistical analysis identified 13 altered isomers in breast cancer. These isomers showed the potential to distinguish breast cancer tissues with an area under the curve (AUC) value above 0.9 in a multivariate receiver operating curve model. Furthermore, the observation of up-regulated 9-oleic acid ester of hydroxy stearic acid (9-OAHSA) and down-regulated 9-hydroxystearic acid (9-HSA) in tumors suggests that breast cancer shares similarities with colorectal cancer, and their potential mechanism is to attenuate the effects of pro-apoptotic 9-HSA by enhancing the synthesis of FAHFAs, thereby promoting tumor survival and progression through this buffering system. Full article

Oleate hydratases (OHs) are of significant industrial interest for the sustainable generation of valuable fine chemicals. When combined with other enzymes in multi-step cascades, the direct formation of fatty acid congeners can be accomplished with minimal processing steps. In this study, two cascade reactions are presented, which can be applied in one-pot approaches. The first cascade was placed “upstream” of an OH derived from Rhodococcus erythropolis (OhyRe), where a lipase from Candida rugosa was applied to hydrolyze triglycerides into free fatty acids, a crucial step for OH conversion. Further, we tested the lipase–OhyRe cascade with various types of renewable triglycerides of plant and microbial origin. In this context, the most efficient conversion was observed for microbial oil from Cutaneotrichosporon oleaginosus leading the way toward its industrial application. In contrast, the second cascade was placed “downstream” of OhyRe, where a novel secondary alcohol dehydrogenase (secADH) was applied to oxidize the hydroxylated fatty acid into a fatty acid ketone. Optimal reaction parameters for the cascade with the secADH were established, which allows this to be applied to high-throughput screens. Moreover, we describe a light-dependent route, thereby extending the catalytic efficiency of the OH enzyme system. Full article

Metallodrugs represent a combination of multifunctionalities that are present concomitantly and can act differently on diverse biotargets. Their efficacy is often related to the lipophilic features exhibited both by long carbo-chains and the phosphine ligands. Three Ru(II) complexes containing hydroxy stearic acids (HSAs) were successfully synthesized in order to evaluate possible synergistic effects between the known antitumor activity of HSA bio-ligands and the metal center. HSAs were reacted with [Ru(H)₂CO(PPh₃)₃] selectively affording O,O-carboxy bidentate complexes. The organometallic species were fully characterized spectroscopically using ESI-MS, IR, UV-Vis, and NMR techniques. The structure of the compound Ru-12-HSA was also determined using single crystal X-ray diffraction. The biological potency of ruthenium complexes (Ru-7-HSA, Ru-9-HSA, and Ru-12-HSA) was studied on human primary cell lines (HT29, HeLa, and IGROV1). To obtain detailed information about anticancer properties, tests for cytotoxicity, cell proliferation, and DNA damage were performed. The results demonstrate that the new ruthenium complexes, Ru-7-HSA and Ru-9-HSA, possess biological activity. Furthermore, we observed that the Ru-9-HSA complex shows increased antitumor activity on colon cancer cells, HT29. Full article

Tomato pomace is a low-cost, renewable resource that has been studied for the extraction of the biopolyester cutin, which is mainly composed of long-chain hydroxy fatty acids. These are excellent building blocks to produce new hydrophobic biopolymers. In this work, the monomers of cutin were extracted and isolated from tomato pomace and utilized to produce cutin-based films. Several strategies for the depolymerization and isolation of monomeric cutin were explored. Strategies differed in the state of the raw material at the beginning of the extraction process, the existence of a tomato peel dewaxing step, the type of solvent used, the type of alkaline hydrolysis, and the isolation method of cutin monomers. These strategies enabled the production of extracts enriched in fatty acids (16-hydroxyhexadecanoic, hexadecanedioic, stearic, and linoleic, among others). Cutin and chitosan-based films were successfully cast from cutin extracts and commercial chitosan. Films were characterized regarding their thickness (0.103 ± 0.004 mm and 0.106 ± 0.005 mm), color, surface morphology, water contact angle (93.37 ± 0.31° and 95.15 ± 0.53°), and water vapor permeability ((3.84 ± 0.39) × 10⁻¹¹ mol·m/m²·s·Pa and (4.91 ± 1.33) × 10⁻¹¹ mol·m/m²·s·Pa). Cutin and chitosan-based films showed great potential to be used in food packaging and provide an application for tomato processing waste. Full article

Lipid components in green coffee were clarified to provide essential data support for green coffee processing. The types, components, and relative contents of lipids in green coffee were first analyzed by ultra-performance liquid chromatography–time-of-flight tandem mass spectrometry (UPLC-TOF-MS/MS). The results showed that the main fatty acids in green coffee were linoleic acid (43.39%), palmitic acid (36.57%), oleic acid (8.22%), and stearic acid (7.37%). Proportionally, the ratio of saturated fatty acids/unsaturated fatty acids/polyunsaturated fatty acids was close to 5.5:1:5.2. A total of 214 lipids were identified, including 15 sterols, 39 sphingosines, 12 free fatty acids, 127 glycerides, and 21 phospholipids. The main components of sterols, sphingosines, free fatty acids, glycerides, and phospholipids were acylhexosyl sitosterol, ceramide esterified omega-hydroxy fatty acid sphingosine, linoleic acid, and triglyceride, respectively. UPLC-TOF-MS/MS furnished high-quality and accurate information on TOF MS and TOF MS/MS spectra, providing a reliable analytical technology platform for analyzing lipid components in green coffee. Full article

Nowadays, diabetes mellitus is one of the most common chronic diseases in the world. Current research on the treatment of diabetes combines many fields of science, such as biotechnology, transplantology or engineering. Therefore, it is necessary to develop new therapeutic strategies and preventive methods. A newly discovered class of lipids—Palmitic Acid Hydroxy Stearic Acid (PAHSA) has recently been proposed as an agent with potential therapeutic properties. In this research, we used an islet-on-a-chip microfluidic 3D model of pancreatic islets (pseudoislets) to study two isomers of PAHSA: 5-PAHSA and 9-PAHSA as potential regulators of proliferation, viability, insulin and glucagon expression, and glucose-stimulated insulin and glucagon secretion. Due to the use of the Lab-on-a-chip systems and flow conditions, we were able to reflect conditions similar to in vivo. In addition, we significantly shortened the time of pseudoislet production, and we were able to carry out cell culture, microscopic analysis and measurements using a multi-well plate reader at the same time on one device. In this report we showed that under microfluidic conditions PAHSA, especially 5-PAHSA, has a positive effect on pseudoislet proliferation, increase in cell number and mass, and glucose-stimulated insulin secretion, which may qualify it as a compound with potential therapeutic properties. Full article

Bitter apple or tumba (Citrullus colocynthis L.) is a prostrate annual herb belonging to the Cucurbitaceae family. It is highly tolerant against multiple abiotic stresses like drought, heat, and soil salinity and can easily grow on very marginal soil, even on sand dunes in hot, arid regions. Tumba fruit is a fleshy berry 5–10 cm in diameter and of a pale yellow color at ripening. The tumba fruit used in this research was harvested from the ICAR-CIAH, Bikaner research farm. The seeds were separated, and their oil was extracted to analyze its physical characteristics and composition (phytochemical compounds, fatty acid profile, etc.). The seeds of the tumba fruit contained 23–25% golden-yellow-colored oil with a specific gravity of 0.92 g/mL. The extracted oil contained appreciable amounts of phytochemical (bioactive) compounds like phenolics (5.39 mg GAE/100 g), flavonoids (938 mg catechin eq./100 g), carotenoids (79.5 mg/kg), oryzanol (0.066%), and lignans (0.012%), along with 70–122 mg AAE/100 g total antioxidant activity (depending on the determination method). The results of fatty acid profiling carried out by GC-MS/MS demonstrated that tumba seed oil contained about 70% unsaturated fatty acids with more than 51% polyunsaturated fatty acids. It mainly contained linoleic acid (C18:2n6; 50.3%), followed by oleic acid (C18:1n9; 18.0%), stearic acid (C18:0; 15.2%), and palmitic acid (C16:0; 12.4%). Therefore, this oil can be considered as a very good source of essential fatty acids like omega-6 fatty acid (linoleic acid), whereas it contains a lower concentration of omega-3 fatty acids (α-linolenic acid) and hydroxy polyunsaturated fatty acids. In addition, it also contains some odd chain fatty acids like pentadecanoic and heptadecanoic acid (C15:0 and C17:0, respectively), which have recently been demonstrated to be bioactive compounds in reducing the risk of cardiometabolic diseases. The results of this study suggest that tumba seed oil contains several health-promoting bioactive compounds with nutraceutical properties; hence, it can be an excellent dietary source. Full article

Lipids modified by oxidative stress are key players in atherosclerosis progression. Superimposed thrombosis with subsequent closure of the coronary artery leads to the clinical manifestation of acute coronary syndrome (ACS). While several studies focusing on alterations in lipid metabolism in the acute phase have been conducted, no information is available on patients’ lipidome alterations over longer time periods. In the current follow-up study, we analyzed plasma samples obtained from 17 patients three years after their ACS event (group AC). Originally, these patients were sampled 3–5 days after an index event (group B). Lipidome stability over time was studied by untargeted lipidomics using high performance liquid chromatography coupled to high resolution mass spectrometry (UHPLC–HRMS). Multi-dimensional statistics used for data processing indicated that plasmalogen lipids were the most prominent lipids separating the above patient groups and that they increased in the follow-up AC group. A similar trend was observed for lysophosphatidylethanolamine (LPE) and phosphatidylethanolamine (PE). The opposite trend was observed for two fatty acyls of hydroxy fatty acid (FAHFAs) lipids and free stearic acid. In addition, a decrease in the “classic” oxitadive stress marker, malondialdehyde (MDA), occurred during the follow-up period. Our findings present unique information about long-term lipidome changes in patients after ACS. Full article

Fatty acid esters of hydroxy fatty acids (FAHFAs) are a new class of endogenous lipids with interesting physiological functions in mammals. Despite their structural diversity and links with nuclear factor erythroid 2-related factor 2 (NRF2) biosynthesis, FAHFAs are less explored as NRF2 activators. Herein, we examined for the first time the synthetic docosahexaenoic acid esters of 12-hydroxy stearic acid (12-DHAHSA) or oleic acid (12-DHAHOA) against NRF2 activation in cultured human hepatoma-derived cells (C3A). The effect of DHA-derived FAHFAs on lipid metabolism was explored by the nontargeted lipidomic analysis using liquid chromatography-mass spectrometry. Furthermore, their action on lipid droplet (LD) oxidation was investigated by the fluorescence imaging technique. The DHA-derived FAHFAs showed less cytotoxicity compared to their native fatty acids and activated the NRF2 in a dose-dependent pattern. Treatment of 12-DHAHOA with C3A cells upregulated the cellular triacylglycerol levels by 17-fold compared to the untreated group. Fluorescence imaging analysis also revealed the suppression of the degree of LDs oxidation upon treatment with 12-DHAHSA. Overall, these results suggest that DHA-derived FAHFAs as novel and potent activators of NRF2 with plausible antioxidant function. Full article

Fatty Acyl esters of Hydroxy Fatty Acids (FAHFA) encompass three different lipid families which have incorrectly been classified as wax esters. These families include (i) Branched-chain FAHFAs, involved in the regulation of glucose metabolism and inflammation, with acylation of an internal branched-chain hydroxy-palmitic or -stearic acid; (ii) ω-FAHFAs, which function as biosurfactants in a number of biofluids, are formed via acylation of the ω-hydroxyl group of very-long-chain fatty acids (these lipids have also been designated as o-acyl hydroxy fatty acids; OAHFA); and (iii) Ornithine-FAHFAs are bacterial lipids formed by the acylation of short-chain 3-hydroxy fatty acids and the addition of ornithine to the free carboxy group of the hydroxy fatty acid. The differences in biosynthetic pathways and cellular functions of these lipid families will be reviewed and compared to wax esters, which are formed by the acylation of a fatty alcohol, not a hydroxy fatty acid. In summary, FAHFA lipid families are both unique and complex in their biosynthesis and their biological actions. We have only evaluated the tip of the iceberg and much more exciting research is required to understand these lipids in health and disease. Full article

Olive oil is an important product in the Mediterranean diet, due to its health benefits and sensorial characteristics. Picholine marocaine is the most cultivated variety in Morocco. The present research aims to evaluate the phenolic compounds, vitamin E and fatty acids of commercial Picholine marocaine virgin olive oils (VOOs) from five different North Moroccan provinces (Chefchaouen, Taounate, Errachidia, Beni Mellal and Taza), using HPLC-photodiode array (PDA)/electrospray ionization (ESI)-MS, normal phase (NP)-HPLC/ fluorescence detector (FLD) and GC-flame ionization detector (FID)/MS, respectively. The obtained results showed an average content of 130.0 mg kg⁻¹ of secoiridoids (oleuropein aglycone, 10-hydroxy-oleuropein aglycone and ligstroside aglycone, oleocanthal and oleacein), 108.1 mg kg⁻¹ of phenolic alcohols (tyrosol and hydroxytyrosol), 34.7 mg kg⁻¹ of phenolic acids (caffeic acid, ferulic acid and elenolic acid), and 8.24 mg kg⁻¹ of flavonoids (luteolin, luteolin glucoside, apigenin). With regard to vitamin E, α-tocopherol was the most abundant vitamin E (57.9 mg kg⁻¹), followed by α-tocotrienol (2.5 mg kg⁻¹), γ-tocopherol (4.5 mg kg⁻¹) and β-tocopherol (1.9 mg kg⁻¹), while δ-tocopherol was not detected. Moreover, 14 fatty acids were found and, among them, oleic acid (76.1%), linoleic acid (8.1%) palmitic acid (8.7%) and stearic acid (2.5%) were the major fatty acids detected. Finally, heat map and principal component analysis allowed us to classify the studied provinces in terms of VOO chemical composition: Chefchaouen (tyrosol and hydroxytyrosol), Taounate (oleuropein aglycone), Errachidia (ferulic acid, w-3 and w-6), Beni Mellal (oleocanthal) and Taza (luteolin and oleic acid). Full article

Nonalcoholic fatty liver disease (NAFLD) is quickly becoming the most common liver disease worldwide. Within the NAFLD spectrum, patients with nonalcoholic steatohepatitis (NASH) are at the highest risk of developing cirrhosis and disease progression to hepatocellular carcinoma. To date, therapeutic options for NASH patients have been ineffective, and therefore, new options are urgently needed. Hence, a model system to develop new therapeutic interventions is needed. Here, we introduce two new in vitro models of steatosis induction in HepG2 cells and primary murine hepatocytes. We used a recently discovered novel class of bioactive anti-inflammatory lipids called branched fatty acid esters of hydroxyl fatty acids. Among these bioactive lipids, palmitic-acid-9-hydroxy-stearic-acid (9-PAHSA) is the most promising as a representative nondrug therapy based on dietary supplements or nutritional modifications. In this study, we show a therapeutic effect of 9-PAHSA on lipotoxicity in steatotic primary hepatocytes and HepG2 cells. This could be shown be increased viability and decreased steatosis. Furthermore, we could demonstrate a preventive effect in HepG2 cells. The outcome of 9-PAHSA administration is both preventative and therapeutically effective for hepatocytes with limited damage. In conclusion, bioactive lipids like 9-PAHSA offer new hope for prevention or treatment in patients with fatty liver and steatosis. Full article

A liquid chromatography–high resolution mass spectrometry (LC-HRMS) method for the direct determination of various saturated hydroxy fatty acids (HFAs) in milk was developed for the first time. The method involves mild sample preparation conditions, avoids time-consuming derivatization procedures, and permits the simultaneous determination of 19 free HFAs in a single 10-min run. This method was validated and applied in 17 cow milk and 12 goat milk samples. This work revealed the existence of various previously unrecognized hydroxylated positional isomers of palmitic acid and stearic acid in both cow and goat milk, expanding our knowledge on the lipidome of milk. The most abundant free HFAs in cow milk were proven to be 7-hydroxystearic acid (7HSA) and 10-hydroxystearic acid (10HSA) (mean content values of 175.1 ± 3.4 µg/mL and 72.4 ± 6.1 µg/mL in fresh milk, respectively). The contents of 7HSA in cow milk seem to be substantially higher than those in goat milk. Full article