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GeroScience Aug 2021To evaluate whether a peculiar plasma profile of fatty acids and endocannabinoidome (eCBome)-related mediators may be associated to longevity, we assessed them in...
To evaluate whether a peculiar plasma profile of fatty acids and endocannabinoidome (eCBome)-related mediators may be associated to longevity, we assessed them in octogenarians (Old; n=42) living in the east-central mountain area of Sardinia, a High-Longevity Zone (HLZ), compared to sexagenarian (Young; n=21) subjects from the same area, and to Olds (n=22) from the Northern Sardinia indicated as Lower-Longevity Zone (LLZ). We found significant increases in conjugated linoleic acid (CLA) and heptadecanoic acid (17:0) levels in Old-HLZ with respect to younger subjects and Old-LLZ subjects. Young-HLZ subjects exhibited higher circulating levels of pentadecanoic acid (15:0) and retinol. Palmitoleic acid (POA) was elevated in both Young and Old subjects from the HLZ. eCBome profile showed a significantly increased plasma level of the two endocannabinoids, N-arachidonoyl-ethanolamine (AEA) and 2-arachidonoyl-glycerol (2-AG) in Old-HLZ subjects compared to Young-HLZ and Old-LLZ respectively. In addition, we found increased N-oleoyl-ethanolamine (OEA), 2-linoleoyl-glycerol (2-LG) and 2-oleoyl-glycerol (2-OG) levels in Old-HLZ group with respect to Young-HLZ (as for OEA an d 2-LG) and both the Old-LLZ and Young-HLZ for 2-OG. The endogenous metabolite of docosahexaenoic acid (DHA), N-docosahexaenoyl-ethanolamine (DHEA) was significantly increased in Old-HLZ subjects. In conclusion, our results suggest that in the HLZ area, Young and Old subjects exhibited a favourable, albeit distinctive, fatty acids and eCBome profile that may be indicative of a metabolic pattern potentially protective from adverse chronic conditions. These factors could point to a suitable physiological metabolic pattern that may counteract the adverse stimuli leading to age-related disorders such as neurodegenerative and metabolic diseases.
Topics: Aged, 80 and over; Ethanolamine; Ethanolamines; Fatty Acids; Humans; Italy; Longevity; Oleic Acids
PubMed: 33650014
DOI: 10.1007/s11357-021-00342-0 -
American Journal of Translational... 2020Sarcopenia is an age-associated disorder that results in skeletal muscle loss. Apoptosis and inflammation are the two major contributors to sarcopenia. Emerging evidence...
Sarcopenia is an age-associated disorder that results in skeletal muscle loss. Apoptosis and inflammation are the two major contributors to sarcopenia. Emerging evidence has shown that long-chain fatty acids (LCFAs) are implicated in the muscles of sarcopenic animal models. However, it is unknown whether LCFAs are correlated with apoptosis or inflammation in the pathogenesis of sarcopenia. Herein, we found that pentadecanoic acid (PDA), a C15 LCFA, was significantly accumulated in human sarcopenic muscles. PDA treatment could dose-dependently induce the expression of the transcription factor (forkhead box M1) and several proapoptotic genes, such as (p53-upregulated modulator of apoptosis), (B-cell/lymphoma 2-associated X) and (apoptotic peptidase activating factor 1), thereby causing apoptosis. Mechanically, PDA activated AKT1 (AKT serine/threonine kinase 1) to phosphorylate NCOR1 (nuclear receptor corepressor 1). The phosphorylated NCOR1 disassociated from the NCOR1-FOXM1 transcriptional complex and could not repress FOXM1-mediated transcription, leading to the induction of . The activated PUMA further triggered downstream apoptotic signaling, including activation of the BAX, APAF1 and caspase cascades, leading to the occurrence of apoptosis. Alkaline phosphatase or knockdown of reversed the FOXM1-mediated apoptotic signaling. Collectively, our results provide new evidence that LCFAs are involved in the pathogenesis of sarcopenia by activating apoptotic signaling. Attempts to decrease the intake of PDA-containing foods or blocking AKT1 may improve the symptoms of sarcopenia.
PubMed: 33042406
DOI: No ID Found -
Circulation Journal : Official Journal... 2015
Predicting cardiac and all-cause death in asymptomatic patients on hemodialysis – importance of training in interpretation of β-methyl iodophenyl-pentadecanoic acid single-photon emission computed tomography (BMIPP SPECT) imaging.
Topics: Fatty Acids; Female; Heart; Humans; Male; Myocardial Ischemia; Myocardium; Observer Variation; Renal Dialysis; Tomography, Emission-Computed, Single-Photon
PubMed: 25452100
DOI: 10.1253/circj.CJ-14-1238 -
Bioresources and Bioprocessing Apr 2021An active site is normally located inside enzymes, hence substrates should go through a tunnel to access the active site. Tunnel engineering is a powerful strategy for...
An active site is normally located inside enzymes, hence substrates should go through a tunnel to access the active site. Tunnel engineering is a powerful strategy for refining the catalytic properties of enzymes. Here, P450HI (Q85H/V170I) derived from hydroxylase P450 from Bacillus subtilis was chosen as the study model, which is reported as a potential decarboxylase. However, this enzyme showed low decarboxylase activity towards long-chain fatty acids. Here, a tunnel engineering campaign was performed for modulating the substrate preference and improving the decarboxylation activity of P450HI. The finally obtained BsβHI-F79A variant had a 15.2-fold improved conversion for palmitic acid; BsβHI-F173V variant had a 3.9-fold improved conversion for pentadecanoic acid. The study demonstrates how the substrate preference can be modulated by tunnel engineering strategy.
PubMed: 38650198
DOI: 10.1186/s40643-021-00379-1 -
Biomedicines Sep 2022Potassium helps to maintain the water-electrolyte and acid-base balance. There is little research on the relationship between plasma fatty acids (FAs), inflammatory...
Potassium helps to maintain the water-electrolyte and acid-base balance. There is little research on the relationship between plasma fatty acids (FAs), inflammatory mediators and red blood cell potassium levels in women with polycystic ovary syndrome (PCOS). This study included 38 Caucasian women with PCOS. Potassium in the erythrocytes was determined by inductively coupled atomic plasma emission spectrometry. The FAs were analysed with gas chromatography, and liquid chromatography was used to separate the eicosanoids. The relationships between the potassium content and the amounts of fatty acids, as well as potassium and arachidonic acid (AAs) derivatives, were analysed. Significant negative correlations were found with, among others, pentadecanoic acid, palmitic acid, stearic acid and arachidic acid, whereas a positive correlation was found with neuronic acid. Positive correlations were observed with 9, 13 HODE (derivatives synthetized from linolenic acid) and 5 oxo ETE and 5 HETE (from 5 LOX pathway). Saturated fatty acids reduce the influx of potassium into the cell by destabilizing the pH of the cytosol, and thus exacerbating the inflammatory response through the activation of the AA cascade. Therefore, improving the flow of potassium inside the cell is important in the treatment of patients.
PubMed: 36140345
DOI: 10.3390/biomedicines10092244 -
MBio May 2020utilizes the fatty acid (FA) kinase system to activate exogenous FAs for membrane synthesis. We developed a lipidomics workflow to determine the membrane...
utilizes the fatty acid (FA) kinase system to activate exogenous FAs for membrane synthesis. We developed a lipidomics workflow to determine the membrane phosphatidylglycerol (PG) molecular species synthesized by at the thigh infection site. Wild-type utilizes both host palmitate and oleate to acylate the 1 position of PG, and the 2 position is occupied by pentadecanoic acid arising from biosynthesis. Inactivation of FakB2 eliminates the ability to assimilate oleate and inactivation of FakB1 reduces the content of saturated FAs and enhances oleate utilization. Elimination of FA activation in either Δ or Δ Δ mutants does not impact growth. All strains recovered from the thigh have significantly reduced branched-chain FAs and increased even-chain FAs compared to that with growth in rich laboratory medium. The molecular species pattern observed in the thigh was reproduced in the laboratory by growth in isoleucine-deficient medium containing exogenous FAs. utilizes specific host FAs for membrane biosynthesis but also requires FA biosynthesis initiated by isoleucine (or leucine) to produce pentadecanoic acid. The shortage of antibiotics against drug-resistant has led to the development of new drugs targeting the elongation cycle of fatty acid (FA) synthesis that are progressing toward the clinic. An objection to the use of FA synthesis inhibitors is that can utilize exogenous FAs to construct its membrane, suggesting that the bacterium would bypass these therapeutics by utilizing host FAs instead. We developed a mass spectrometry workflow to determine the composition of the membrane at the infection site to directly address how uses host FAs. strains that cannot acquire host FAs are as effective in establishing an infection as the wild type, but strains that require the utilization of host FAs for growth were attenuated in the mouse thigh infection model. We find that does utilize host FAs to construct its membrane, but host FAs do not replace the requirement for pentadecanoic acid, a branched-chain FA derived from isoleucine (or leucine) that predominantly occupies the 2 position of phospholipids. The membrane phospholipid structure of mutants that cannot utilize host FAs indicates the isoleucine is a scarce resource at the infection site. This reliance on the synthesis of predominantly pentadecanoic acid that cannot be obtained from the host is one reason why drugs that target fatty acid synthesis are effective in treating infections.
Topics: Animals; Culture Media; Fatty Acids; Female; Host Microbial Interactions; Isoleucine; Mass Spectrometry; Mice; Mice, Inbred BALB C; Oleic Acid; Phosphatidylglycerols; Staphylococcal Infections; Staphylococcus aureus; Thigh
PubMed: 32430471
DOI: 10.1128/mBio.00920-20 -
Applied and Environmental Microbiology Mar 2009Nitrate-reducing enrichments, amended with n-hexadecane, were established with petroleum-contaminated sediment from Onondaga Lake. Cultures were serially diluted to...
Nitrate-reducing enrichments, amended with n-hexadecane, were established with petroleum-contaminated sediment from Onondaga Lake. Cultures were serially diluted to yield a sediment-free consortium. Clone libraries and denaturing gradient gel electrophoresis analysis of 16S rRNA gene community PCR products indicated the presence of uncultured alpha- and betaproteobacteria similar to those detected in contaminated, denitrifying environments. Cultures were incubated with H(34)-hexadecane, fully deuterated hexadecane (d(34)-hexadecane), or H(34)-hexadecane and NaH(13)CO(3). Gas chromatography-mass spectrometry analysis of silylated metabolites resulted in the identification of [H(29)]pentadecanoic acid, [H(25)]tridecanoic acid, [1-(13)C]pentadecanoic acid, [3-(13)C]heptadecanoic acid, [3-(13)C]10-methylheptadecanoic acid, and d(27)-pentadecanoic, d(25)-, and d(2)(4)-tridecanoic acids. The identification of these metabolites suggests a carbon addition at the C-3 position of hexadecane, with subsequent beta-oxidation and transformation reactions (chain elongation and C-10 methylation) that predominantly produce fatty acids with odd numbers of carbons. Mineralization of [1-(14)C]hexadecane was demonstrated based on the recovery of (14)CO(2) in active cultures.
Topics: Alkanes; Alphaproteobacteria; Anaerobiosis; Betaproteobacteria; Biodegradation, Environmental; Carboxylic Acids; DNA, Bacterial; DNA, Ribosomal; Genes, rRNA; Geologic Sediments; Mass Spectrometry; Molecular Sequence Data; RNA, Bacterial; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Sequence Homology, Nucleic Acid
PubMed: 19114507
DOI: 10.1128/AEM.02491-08 -
Frontiers in Nutrition 2023Diets high in glucose or fat contribute to an increased prevalence of the diseases. Therefore, the objective of the current research was to observe and evaluate the...
OBJECTIVE
Diets high in glucose or fat contribute to an increased prevalence of the diseases. Therefore, the objective of the current research was to observe and evaluate the impact of dietary components on different metabolomic profiles in primary tissues of mice.
METHODS
For 8 weeks, diet with high-glucose or-fat was given to C57BL/6 J mice. The levels of metabolites in the primary tissues of mice were studied using gas chromatography-mass spectrometry (GC-MS) and analyzed using multivariate statistics.
RESULTS
By comparing the metabolic profiles between the two diet groups and control group in mice main tissues, our study revealed 32 metabolites in the high-glucose diet (HGD) group and 28 metabolites in the high-fat diet (HFD) group. The most significantly altered metabolites were amino acids (AAs; L-alanine, L-valine, glycine, L-aspartic acid, L-isoleucine, L-leucine, L-threonine, L-glutamic acid, phenylalanine, tyrosine, serine, proline, and lysine), fatty acids (FAs; propanoic acid, 9,12-octadecadienoic acid, pentadecanoic acid, hexanoic acid, and myristic acid), and organic compounds (succinic acid, malic acid, citric acid, L-(+)-lactic acid, myo-inositol, and urea). These metabolites are implicated in many metabolic pathways related to energy, AAs, and lipids metabolism.
CONCLUSION
We systematically analyzed the metabolic changes underlying high-glucose or high-fat diet. The two divergent diets induced patent changes in AA and lipid metabolism in the main tissues, and helped identify metabolic pathways in a mouse model.
PubMed: 37492592
DOI: 10.3389/fnut.2023.1171806 -
Nutrients Mar 2021Most nutrition studies looking at the association of food with cardiometabolic markers rely on food frequency questionnaires, which are prone to recall bias....
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 ( = 0.0474 and = 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.
Topics: Aged; Biomarkers; Body Weight; Cardiovascular Diseases; Dairy Products; Diabetes Mellitus, Type 2; Diet; Fatty Acids, Nonesterified; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Nutrition Assessment; Risk Factors
PubMed: 33807135
DOI: 10.3390/nu13041145