Search Results (21)

There is an urgent need to identify interventions that broadly target aging-related cognitive decline and progression to Alzheimer’s disease (AD). Bottlenose dolphins (Tursiops truncatus) have histologic changes similar to AD in humans, and they also develop shared age-associated co-morbidities identified as risk factors for AD in humans, including type 2 diabetes, ferroptosis, and iron overload, which can be driven by nutritional C15:0 deficiency. We hypothesized that (1) dolphins would have amyloid beta (Aβ) plaques and neuroinflammation that paralleled that of humans in relation to age-related progression, quantitative concentration, and brain region; and (2) C15:0 would have dose-dependent activities relevant to protecting cognitive health. Quantitative immunohistochemistry staining was used to assess 68 tissues from archived brains of 19 Navy dolphins to evaluate associations among amyloid beta (Aβ) plaques and neuroinflammation by brain region, sex, and age group. Further, dose-dependent C15:0 activities, using a third-party panel intended to screen for potential AD therapeutics, were evaluated. Similar to humans, dolphins had the highest Aβ plaque density variation in the hippocampus (90th percentile of 4.95 plaques/mm²), where plaque density increased with age (p = 0.05). All measured markers of neuroinflammation were detected, including the highest concentrations of activated microglia (CD68⁺) in the hippocampus (0.46 ± 0.38 cells/mm²). C15:0 was a dose-dependent inhibitor of two targets, fatty acid amide hydrolase (FAAH) (IC₅₀ 2.5 µM, 89% maximum inhibition at 50 µM relative to URB597) and monoamine oxidase B (MAO-B) (IC₅₀ 19.4 µM, 70% maximum inhibition at 50 µM relative to R(-)-Deprenyl). These activities have demonstrated efficacy against Aβ formation and neuroinflammation, including protection of cognitive function in the hippocampus. These findings suggest that, in addition to protecting against AD co-morbidities, C15:0 may play a distinct role in supporting cognitive health, especially at higher concentrations. Full article

The arid mountainous region of Hail in Saudi Arabia has a variety of desert vegetation, some of which are conventionally used in Bedouin traditional medicine. These plants need scientific examination. This research seeks to examine Blepharis ciliaris using a thorough multi-analytical methodology that includes antibacterial and antioxidant assessments as well as computational modeling. GC–MS analysis of the methanolic extract revealed 17 organic compounds, including pentadecanoic acid, ethyl methyl ester (2.63%); hexadecanoic acid, methyl ester (1.00%); 9,12-octadecadienoic acid (Z,Z)-, methyl ester (2.74%); 9-octadecenoic acid, methyl ester (E) (2.78%); octadecanoic acid (5.88%); 9-tetradecenoic acid (Z) (3.22%); and undec-10-enoic acid, undec-2-n-1-yl ester (5.67%). The DPPH test evaluated antioxidant activity, revealing a notable increase with higher concentrations of the methanolic extract, achieving maximum inhibition of 81.54% at 1000 µg/mL. The methanolic extract exhibited moderate antibacterial activity, with average inhibition zones of 10.33 ± 1.53 mm, 13.33 ± 1.53 mm, 10.67 ± 1.53 mm, and 10.00 ± 2.00 mm against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Serratia marcescens, respectively, as determined by the disk diffusion method. The minimum inhibitory concentration (MIC) values were 500 µg/mL for S. aureus and B. subtilis, whereas E. coli and S. marcescens showed susceptibility at 1000 µg/mL. Computational simulations were employed to assess the toxicity, drug-likeness, and ADMET profiles of compounds derived from Blepharis ciliaris. Thirteen bioactive compounds were assessed in silico against Staphylococcus aureus sortase A (PDB: 1T2O), Bacillus subtilis BsFabHb (PDB: 8VDB), Escherichia coli LPS assembly protein (LptD) (PDB: 4RHB), and a modeled Serratia marcescens outer-membrane protein TolC, focusing on cell wall and membrane structures. Compound 3, (+)-Ascorbic acid 2,6-dihexadecanoate, shown significant binding affinities to B. subtilis BsFabHb, E. coli LPS assembly protein, and S. marcescens TolC. Full article

In recent years, the interest in lipids present in wines has increased, because these natural components, even at low or very low concentrations, play an important role in wine evolution and quality and contribute substantially to the taste and mouthfeel of wines. Herein, we present a liquid chromatography–high-resolution mass spectrometry (LC-HRMS) method for the profiling of free fatty acids (FFAs) in wines. The method is fast and allows the simultaneous determination of twenty-seven saturated and unsaturated FFAs in wine samples, avoiding any prior derivatization step. After validation, a variety of white and rose commercial wine samples from the Greek market, either sparkling or non-sparkling, were analyzed by the present method. The majority of wine FFAs are saturated long aliphatic, in particular palmitic (C16:0) and stearic (C18:0) acids, followed by myristic (C14:0) and pentadecanoic (C15:0) acids, while oleic (C18:1), palmitoleic (C16:1) and linoleic (C18:2) acids were quantified among the unsaturated FAs. The medium-chain C6:0 and the unsaturated C16:1 and C18:2 acids were found at higher concentrations in rose wines compared to white. Full article

Background/Objectives: Dietary fats have been linked to the increasing incidence of chronic diseases, including inflammatory bowel diseases (IBD), namely, Crohn’s disease (CD). Methods: This study investigated the impact of pentadecanoic acid (C15:0), a type of an odd-numbered chain saturated fatty acid, for its potential anti-inflammatory properties in different mouse models of experimental IBD using the SAMP1/YitFc (SAMP) mouse line (14- or 24-week-old), including chronic ileitis and DSS-induced colitis. To quantitively assess the effect of C:15, we tested two dosages of C:15 in selected experiments in comparison to control mice. Intestinal inflammation and intestinal permeability were used as primary outcomes. Results: In ileitis, C:15 supplementation showed an anti-inflammatory effect in SAMP mice (e.g., a reduction in ileitis severity vs. control p < 0.0043), which was reproducible when mice were tested in the DSS model of colitis (e.g., reduced permeability vs. control p < 0.0006). Of relevance, even the short-term C:15 therapy prevented colitis in mice by maintaining body weight, decreasing inflammation, preserving gut integrity, and alleviating colitis signs. Conclusions: Collectively, the findings from both ileitis and colitis in SAMP mice indicate that C:15 may have therapeutic effects in the treatment of IBD (colitis in the short term). This promising effect has major translational potential for the alleviation of IBD in humans. Full article

[¹²³I]β-methyl-p-iodophenyl-pentadecanoic acid ([¹²³I]BMIPP), which is used for nuclear medicine imaging of myocardial fatty acid metabolism, accumulates in cancer cells. However, the mechanism of accumulation remains unknown. Therefore, this study aimed to elucidate the accumulation and accumulation mechanism of [¹²³I]BMIPP in cancer cells. We compared the accumulation of [¹²³I]BMIPP in cancer cells with that of [¹⁸F]FDG and found that [¹²³I]BMIPP was a much higher accumulation than [¹⁸F]FDG. The accumulation of [¹²³I]BMIPP was evaluated in the presence of sulfosuccinimidyl oleate (SSO), a CD36 inhibitor, and lipofermata, a fatty acid transport protein (FATP) inhibitor, under low-temperature conditions and in the presence of etomoxir, a carnitine palmitoyl transferase I (CPT1) inhibitor. The results showed that [¹²³I]BMIPP accumulation was decreased in the presence of SSO and lipofermata in H441, LS180, and DLD-1 cells, suggesting that FATPs and CD36 are involved in [¹²³I]BMIPP uptake in cancer cells. [¹²³I]BMIPP accumulation in all cancer cell lines was significantly decreased at 4 °C compared to that at 37 °C and increased in the presence of etomoxir in all cancer cell lines, suggesting that the accumulation of [¹²³I]BMIPP in cancer cells is metabolically dependent. In a biological distribution study conducted using tumor-bearing mice transplanted with LS180 cells, [¹²³I]BMIPP highly accumulated in not only LS180 cells but also normal tissues and organs (including blood and muscle). The tumor-to-intestine or large intestine ratios of [¹²³I]BMIPP were similar to those of [¹⁸F]FDG, and the tumor-to-large-intestine ratios exceeded 1.0 during 30 min after [¹²³I]BMIPP administration in the in vivo study. [¹²³I]BMIPP is taken up by cancer cells via CD36 and FATP and incorporated into mitochondria via CPT1. Therefore, [¹²³I]BMIPP may be useful for imaging cancers with activated fatty acid metabolism, such as colon cancer. However, the development of novel imaging radiotracers based on the chemical structure analog of [¹²³I]BMIPP is needed. Full article

Ferroptosis is a newly discovered form of cell death caused by the peroxidation of fragile fatty acids in cell membranes, which combines with iron to increase reactive oxygen species and disable mitochondria. Ferroptosis has been linked to aging-related conditions, including type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD). Pentadecanoic acid (C15:0), an odd-chain saturated fat, is an essential fatty acid with the primary roles of stabilizing cell membranes and repairing mitochondrial function. By doing so, C15:0 reverses the underpinnings of ferroptosis. Under the proposed “Cellular Stability Hypothesis”, evidence is provided to show that cell membranes optimally need >0.4% to 0.64% C15:0 to support long-term health and longevity. A pathophysiology of a newly identified nutritional C15:0 deficiency syndrome (“Cellular Fragility Syndrome”) is provided that demonstrates how C15:0 deficiencies (≤0.2% total circulating fatty acids) can increase susceptibilities to ferroptosis, dysmetabolic iron overload syndrome, type 2 diabetes, cardiovascular disease, and NAFLD. Further, evidence is provided that C15:0 supplementation can reverse the described C15:0 deficiency syndrome, including the key components of ferroptosis. Given the declining dietary intake of C15:0, especially among younger generations, there is a need for extensive studies to understand the potential breadth of Cellular Fragility Syndrome across populations. Full article

Pentadecanoic acid (C15:0) is an essential odd-chain saturated fatty acid with broad activities relevant to protecting cardiometabolic, immune, and liver health. C15:0 activates AMPK and inhibits mTOR, both of which are core components of the human longevity pathway. To assess the potential for C15:0 to enhance processes associated with longevity and healthspan, we used human cell-based molecular phenotyping assays to compare C15:0 with three longevity-enhancing candidates: acarbose, metformin, and rapamycin. C15:0 (n = 36 activities in 10 of 12 cell systems) and rapamycin (n = 32 activities in 12 of 12 systems) had the most clinically relevant, dose-dependent activities. At their optimal doses, C15:0 (17 µM) and rapamycin (9 µM) shared 24 activities across 10 cell systems, including anti-inflammatory (e.g., lowered MCP-1, TNFα, IL-10, IL-17A/F), antifibrotic, and anticancer activities, which are further supported by previously published in vitro and in vivo studies. Paired with prior demonstrated abilities for C15:0 to target longevity pathways, hallmarks of aging, aging rate biomarkers, and core components of type 2 diabetes, heart disease, cancer, and nonalcoholic fatty liver disease, our results support C15:0 as an essential nutrient with activities equivalent to, or surpassing, leading longevity-enhancing candidate compounds. 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

Malaysia has a long coastline surrounded by various islands, including North Borneo, that provide a suitable environment for the growth of diverse species of seaweeds. Some of the important North Bornean seaweed species are Kappaphycus alvarezii, Eucheuma denticulatum, Halymenia durvillaei (Rhodophyta), Caulerpa lentillifera, Caulerpa racemosa (Chlorophyta), Dictyota dichotoma and Sargassum polycystum (Ochrophyta). This review aims to highlight the therapeutic potential of North Bornean seaweeds and their nutraceutical profiling. North Bornean seaweeds have demonstrated anti-inflammatory, antioxidant, antimicrobial, anticancer, cardiovascular protective, neuroprotective, renal protective and hepatic protective potentials. The protective roles of the seaweeds might be due to the presence of a wide variety of nutraceuticals, including phthalic anhydride, 3,4-ethylenedioxythiophene, 2-pentylthiophene, furoic acid (K. alvarezii), eicosapentaenoic acid, palmitoleic acid, fucoxanthin, β-carotene (E. denticulatum), eucalyptol, oleic acid, dodecanal, pentadecane (H. durvillaei), canthaxanthin, oleic acid, pentadecanoic acid, eicosane (C. lentillifera), pseudoephedrine, palmitic acid, monocaprin (C. racemosa), dictyohydroperoxide, squalene, fucosterol, saringosterol (D. dichotoma), and lutein, neophytadiene, cholest-4-en-3-one and cis-vaccenic acid (S. polycystum). Extensive studies on the seaweed isolates are highly recommended to understand their bioactivity and mechanisms of action, while highlighting their commercialization potential. Full article

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes, and retinal microaneurysms (MA) are one of the first detected abnormalities associated with DR. We recently showed elevated serum triglyceride levels to be associated with the development of MA in the Finnish Diabetes Prevention Study (DPS). The purpose of this metabolomics study was to assess whether serum fatty acid (FA) composition, plasmalogens, and low-grade inflammation may enhance or decrease the risk of MA. Originally, the DPS included 522 individuals (mean 55 years old, range 40–64 years) with impaired glucose tolerance who were randomized into an intervention (n = 265) or control group (n = 257). The intervention lasted for a median of four years (active period), after which annual follow-up visits were conducted. At least five years after stopping the intervention phase of DPS, participants classified as MA negative (n = 115) or MA positive (n = 51) were included in the current study. All these participants were free of diabetes at baseline (WHO 1985) and had high-sensitive C-reactive protein (hs-CRP), serum FA composition, and selected lipid metabolites measured during the active study period. Among the markers associated with MA, the serum plasmalogen dm16:0 (p = 0.006), the saturated odd-chain FA 15.0 (pentadecanoic acid; p = 0.015), and omega-3 very long-chain FAs (p < 0.05) were associated with a decreased occurrence of MA. These associations were independent of study group and other risk factors. The association of high serum triglycerides with the MA occurrence was attenuated when these MA-associated serum lipid markers were considered. Our findings suggest that, in addition to n-3 FAs, odd-chain FA 15:0 and plasmalogen dm16:0 may contribute to a lower risk of MA in individuals with impaired glucose tolerance. These putative novel lipid biomarkers have an association with MA independently of triglyceride levels. Full article

Odd-chain fatty acids (OCFA) are inversely associated with type-2-diabetes in epidemiological studies. They are considered as a biomarker for dairy intake because fermentation in ruminants yields high amounts of propionate, which is used as the primer for lipogenesis. Recently, we demonstrated endogenous OCFA synthesis from propionate in humans and mice, but how this is affected by microbial colonization is still unexplored. Here, we investigated the effect of increasing microbiota complexity on hepatic lipid metabolism and OCFA levels in different dietary settings. Germ-free (GF), gnotobiotic (SIH, simplified human microbiota) or conventional (CONV) C3H/HeOuJ-mice were fed a CHOW or high-fat diet with inulin (HFI) to induce microbial fermentation. We found that hepatic lipogenesis was increased with increasing microbiota complexity, independently of diet. In contrast, OCFA formation was affected by diet as well as microbiota. On CHOW, hepatic OCFA and intestinal gluconeogenesis decreased with increasing microbiota complexity (GF > SIH > CONV), while cecal propionate showed a negative correlation with hepatic OCFA. On HFI, OCFA levels were highest in SIH and positively correlated with cecal propionate. The propionate content in the CHOW diet was 10 times higher than that of HFI. We conclude that bacterial propionate production affects hepatic OCFA formation, unless this effect is masked by dietary propionate intake. Full article

Most nutrition studies looking at the association of food with cardiometabolic markers rely on food frequency questionnaires, which are prone to recall bias. Pentadecanoic acid, heptadecanoic acid and trans-palmitoleic acid are fatty acids that are not synthesized endogenously but are obtained from the diet, particularly dairy, making them reasonable biomarkers of dairy consumption. We investigated the association of dairy fatty acid biomarkers with glycated hemoglobin (HbA1c) and cardiovascular risk factors in type 2 diabetes (T2D). In a clinical trial, 111 participants with T2D (age 58.5 ± 8.9 years, HbA1c 8.09 ± 0.96%) were randomized into three groups: a control group that maintained baseline dairy intake, a low-fat (LF) group that incorporated ≥3 servings/day of LF dairy and a high-fat (HF) group that incorporated ≥3 servings/day of HF dairy. We compared the fatty acids (FA) composition between the three groups at 24 weeks. Pentadecanoic acid and trans-palmitoleic acid increased in the HF group by 14.1% ± 5.4% and 17.5% ± 5.1%, respectively, but not in the control and LF groups (p = 0.0474 and p = 0.0025 for group-by-time interaction, respectively). Those increases were positively associated with changes in total cholesterol, very-low-density lipoprotein cholesterol VLDL-C and triglycerides but were not associated with changes in HbA1c from baseline to 24 weeks. These results suggest that the intervention was successful and that participants were likely compliant, which supports the validity of the main trial. Full article

Virgin coconut oil (VCO) can be prepared with or without heat. Fermentation and centrifuge processes can be done without the use of heat (cold process), while expelling involves heat due to friction. Volatile organic compounds (VOCs) from VCO samples prepared using these three methods were collected using solid phase microextraction (SPME) and analyzed using gas chromatography–mass spectrometry (GC-MS). Twenty-seven VCO samples from nine VCO producers were analyzed. The VOCs from refined, bleached, and deodorized coconut oil (RBDCO) were also obtained for comparison. Fourteen compounds were found to be common in more than 80% of the VCO samples analyzed. These included: Acetic acid; C6, C8, C10, C12, and C14 fatty acids, and their corresponding delta-lactones; and C8, C10 and C12 ethyl carboxylates. Fourteen minor VOCs were likewise detected which can be grouped into five types: Carboxylic acids (formic acid, butanoic acid, benzoic acid, and pentadecanoic acid), ketones (acetoin, 2-heptanone), an alcohol (ethanol), aldehydes (acetaldehyde, hexanal, benzaldehyde), esters (ethyl acetate, methyl tetradecanoate), and hydrocarbons (n-hexane and toluene). Five pyrazines were detected in expeller VCO. Various hydrocarbons from C5 to C14 were noted to be higher in old RBDCO and VCO samples. There were variations in the VOCs within each VCO process as each producer used different processing times, temperatures, and drying procedures. Principal components analysis (PCA) was able to group the samples according to the process used, but there were overlaps which may be due to variations in the specific procedures used by the manufacturers. These results may help VCO manufacturers control their production processes. Full article

The transition from pregnancy to lactation is characterized by a progressive decrease in insulin sensitivity. Propionate increases with dietary fiber consumption and has been shown to improve insulin sensitivity. Recent studies suggest that plasma odd-chain fatty acids [OCFAs; pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0)] that inversely correlated with insulin resistance are synthesized endogenously from gut-derived propionate. The present study investigated the effects of soluble fiber during gestation on gut microbiota, plasma non-esterified fatty acids and insulin sensitivity in sows. Sows were allocated to either control or 2.0% guar gum plus pregelatinized waxy maize starch (SF) dietary treatment during gestation. The SF addition changes the structure and composition of gut microbiota in sows. Genus Eubacterium increased by SF addition may promote intestinal propionate production. Moreover, the dietary SF increased circulating levels of plasma OCFAs, especially C17:0. The SF-fed sows had a higher insulin sensitivity and a lower systemic inflammation level during perinatal period. Furthermore, the plasma C15:0 and C17:0 was negatively correlated with the area under curve of plasma glucose after meal and plasma interleukin-6. In conclusion, dietary SF improves insulin sensitivity and alleviates systemic inflammation in perinatal sows, potentially related to its stimulating effect on propionate and OCFAs production. Full article

A number of reports have indicated a relationship between bacterial resistance to antibiotics and their lipid composition. In the present study, we characterized the lipid profiles of American Type Culture Collection (ATCC) and clinical strains of Staphylococcus aureus and its correlation with antibiotic resistance and hydrophobicity. The following strains were used: S. aureus ATCC 6538P, S. aureus ATCC 43300 (MRSA), seven clinical strains from the pharynges, two strains from duodenal ulcers, four strains from hip prostheses, and one strain from the conjunctiva. Lipid-related differentiation was observed across the S. aureus strains: the higher abundance of anteiso-pentadecanoic acid (anteiso-C_15:0) and anteiso-heptadecanoic acid (anteiso-C_17:0), followed by iso-pentadecanoic acid (iso-C_15:0), suggested that these were common lipids. Iso-tridecanoic acid (iso-C_13:0) and anteiso-tridecanoic acid (anteiso-C_13:0), iso-hexadecanoic acid (iso-C_16:0) and anteiso-hexadecanoic acid (anteiso-C_16:0), and all forms of octadecanoic acid (C_18:0) were usually detected in low abundance. Strains isolated from pharynges showed the highest ratio of branched/straight chains. A distinction in two clusters based on the amount and type of bacterial lipids identified was obtained, which correlated to the antibiotic resistance, the strains origin, and the cell-surface hydrophobicity. We report a potential correlation between the lipid profile of S. aureus strains, site of infection, antibiotic resistance, and cell-surface hydrophobicity. These results, which still need further insights, could be a first step to identifying antibiotic resistance in response to environmental adaptation. Full article