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Nutrients Nov 2018Pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) have been described as dietary biomarkers of dairy-fat consumption, with varying degrees of reliability between...
Pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) have been described as dietary biomarkers of dairy-fat consumption, with varying degrees of reliability between studies. It remains unclear how the total amount of dietary fat, representing one of the main confounding factors in these biomarker investigations, affects C15:0 and C17:0 circulating concentrations independent of their relative intake. Additionally, it is not clear how changes in the dietary total-fat affects other fatty acids in circulation. Through two dietary studies with different total-fat levels but maintaining identical fatty acid compositions, we were able to see how the dietary total-fat affects the fatty acids in circulation. We saw that there was a statistically significant, proportionate, and robust decrease in the endogenous C15:0 levels with an increase in dietary total-fat. However, there was no significant change in the circulating C17:0 concentrations as the total-fat increased. To conclude, the dietary total-fat content and fat-type have a very complex influence on the relative compositions of circulating fatty acids, which are independent of the actual dietary fatty acid composition. Knowing how to manipulate circulating C15:0 and C17:0 concentrations is far-reaching in nutritional/pathological research as they highlight a dietary route to attenuate the development of metabolic disease (both by reducing risk and improving prognosis).
Topics: Animals; Biomarkers; Diet; Dietary Fats; Fatty Acids; Gas Chromatography-Mass Spectrometry; Male; Rats; Rats, Sprague-Dawley; Rats, Wistar
PubMed: 30400275
DOI: 10.3390/nu10111646 -
The American Journal of Clinical... Sep 2018Controversy has emerged about the benefits compared with harms of dairy fat, including concerns over long-term effects. Previous observational studies have assessed...
BACKGROUND
Controversy has emerged about the benefits compared with harms of dairy fat, including concerns over long-term effects. Previous observational studies have assessed self-reported estimates of consumption or a single biomarker measure at baseline, which may lead to suboptimal estimation of true risk.
OBJECTIVE
The aim of this study was to investigate prospective associations of serial measures of plasma phospholipid fatty acids pentadecanoic (15:0), heptadecanoic (17:0), and trans-palmitoleic (trans-16:1n-7) acids with total mortality, cause-specific mortality, and cardiovascular disease (CVD) risk among older adults.
DESIGN
Among 2907 US adults aged ≥65 y and free of CVD at baseline, circulating fatty acid concentrations were measured serially at baseline, 6 y, and 13 y. Deaths and CVD events were assessed and adjudicated centrally. Prospective associations were assessed by multivariate-adjusted Cox models incorporating time-dependent exposures and covariates.
RESULTS
During 22 y of follow-up, 2428 deaths occurred, including 833 from CVD, 1595 from non-CVD causes, and 1301 incident CVD events. In multivariable models, circulating pentadecanoic, heptadecanoic, and trans-palmitoleic acids were not significantly associated with total mortality, with extreme-quintile HRs of 1.05 for pentadecanoic (95% CI: 0.91, 1.22), 1.07 for heptadecanoic (95% CI: 0.93, 1.23), and 1.05 for trans-palmitoleic (95% CI: 0.91, 1.20) acids. Circulating heptadecanoic acid was associated with lower CVD mortality (extreme-quintile HR: 0.77; 95% CI: 0.61, 0.98), especially stroke mortality, with a 42% lower risk when comparing extreme quintiles of heptadecanoic acid concentrations (HR: 0.58; 95% CI: 0.35, 0.97). In contrast, heptadecanoic acid was associated with a higher risk of non-CVD mortality (HR: 1.27; 95% CI: 1.07, 1.52), which was not clearly related to any single subtype of non-CVD death. No significant associations of pentadecanoic, heptadecanoic, or trans-palmitoleic acids were seen for total incident CVD, coronary heart disease, or stroke.
CONCLUSIONS
Long-term exposure to circulating phospholipid pentadecanoic, heptadecanoic, or trans-palmitoleic acids was not significantly associated with total mortality or incident CVD among older adults. High circulating heptadecanoic acid was inversely associated with CVD and stroke mortality and potentially associated with higher risk of non-CVD death.
Topics: Aged; Biomarkers; Cardiovascular Diseases; Cause of Death; Dairy Products; Dietary Fats; Fatty Acids; Fatty Acids, Monounsaturated; Humans; Prospective Studies; Risk Factors; Stroke
PubMed: 30007304
DOI: 10.1093/ajcn/nqy117 -
Omics : a Journal of Integrative Biology Aug 2016Fatty acids are important sources of energy and possible predictors and etiologic factors in many common complex pathologies such as cardiovascular disease, diabetes,...
Fatty acids are important sources of energy and possible predictors and etiologic factors in many common complex pathologies such as cardiovascular disease, diabetes, and certain forms of cancers. While fatty acids are thought to covary with each other, their underlying causal networks have not been fully elucidated. This study reports the identification and analysis of a statistical causal network among 15 mostly long-chain fatty acids. In an African-American population sample and using the Genome granularity-Directed Acyclic Graph (GDAG) algorithm, we determined directions or causal relationships in the fatty acid metabolome. A directed causal network was constructed that revealed 29 significant edges among the 15 nodes (p < 0.001). We report that two fatty acid metabolites, palmitoleate and margarate, which originate from dietary intake, together influence every other fatty acid in the network. On the other hand, despite its high connectivity, dihomo-linoleate did not appear to play an important role over the whole fatty acid network. These findings collectively suggest possible strategic entry points for new treatments or preventive modalities against diseases affected by fatty acid metabolites such as cardiovascular disease, diabetes, and obesity. Further studies examining the embedded substructure of the fatty acid metabolite networks in independent population samples would be timely and warranted as we move toward novel postgenomic diagnostics and therapeutics.
Topics: Black or African American; Algorithms; Atherosclerosis; Cardiovascular Diseases; Diabetes Mellitus; Dietary Fats; Fasting; Fatty Acids; Fatty Acids, Monounsaturated; Humans; Metabolic Networks and Pathways; Metabolome; Obesity; Polymorphism, Single Nucleotide
PubMed: 27501297
DOI: 10.1089/omi.2016.0071 -
BMC Complementary Medicine and Therapies Oct 2020In traditional Malay medicine, Marantodes pumilum (Blume) Kuntze (family Primulaceae) is commonly used by women to treat parturition, flatulence, dysentery,...
BACKGROUND
In traditional Malay medicine, Marantodes pumilum (Blume) Kuntze (family Primulaceae) is commonly used by women to treat parturition, flatulence, dysentery, dysmenorrhea, gonorrhea, and bone diseases. Preliminary screening of some Primulaceae species showed that they possess xanthine oxidase inhibitory activity. Thus, this study aimed to investigate the xanthine oxidase inhibitory activity of three varieties of M. pumilum and their phytochemical compounds.
METHOD
Dichloromethane, methanol, and water extracts of the leaves and roots of M. pumilum var. alata, M. pumilum var. pumila, and M. pumilum var. lanceolata were tested using an in vitro xanthine oxidase inhibitory assay. Bioassay-guided fractionation and isolation were carried out on the most active extract using chromatographic techniques. The structures of the isolated compounds were determined using spectroscopic techniques.
RESULTS
The most active dichloromethane extract of M. pumilum var. pumila leaves (IC = 161.6 μg/mL) yielded one new compound, 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin (1), and five known compounds, viz. ardisiaquinone A (2), maesanin (3), stigmasterol (4), tetracosane (5), and margaric acid (6). The new compound was found to be the most active xanthine oxidase inhibitor with an IC value of 0.66 ± 0.01 μg/mL, which was not significantly different (p > 0.05) from that of the positive control, allopurinol (IC = 0.24 ± 0.00 μg/mL).
CONCLUSION
This study suggests that the new compound 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin (1), which was isolated from the dichloromethane extract of M. pumilum var. pumila leaves, could be a potential xanthine oxidase inhibitor.
Topics: Humans; In Vitro Techniques; Isocoumarins; Malaysia; Plant Extracts; Plant Leaves; Plant Roots; Primulaceae; Xanthine Oxidase
PubMed: 33109178
DOI: 10.1186/s12906-020-03119-8 -
Nutrition, Metabolism, and... Dec 2012Despite their relatively high content of saturated fat, studies of dairy product intake and the risk of cardiovascular disease have often yielded null or inverse...
BACKGROUND AND AIMS
Despite their relatively high content of saturated fat, studies of dairy product intake and the risk of cardiovascular disease have often yielded null or inverse results. The use of fatty acid biomarkers to reflect dairy intake could elucidate this association. This study aims to evaluate the association between dairy intake, assessed by adipose pentadecanoic (15:0) and heptadecanoic (17:0) fatty acids and food frequency questionnaire (FFQ), and the risk of nonfatal myocardial infarction (MI), in a matched case-control study of Costa Rican adults (n=3630).
METHODS AND RESULTS
The association was examined using conditional logistic regression, adjusted for potential confounders. The associations of adipose tissue 15:0 and 17:0 with the risk of MI were not statistically significant (for 15:0: multivariate-adjusted OR for 5th quintile vs. 1st=1.14 (95% CI=0.85, 1.53), p-value for linear trend=0.77; for 17:0: multivariate-adjusted OR for 5th quintile vs. 1st=1.15 (95% CI=0.88, 1.51), p-value for linear trend=0.18). The association between the FFQ measure of dairy intake and MI showed evidence of a possible threshold effect, with a protective association observed for all but the top quintile of the exposure distribution.
CONCLUSION
Dairy product intake as assessed by adipose tissue 15:0, 17:0, and by FFQ is not associated with a linear increase in the risk of MI in the study population. It is possible that the adverse effect of saturated fat in dairy products on cardiovascular health is offset by presence of beneficial nutrients.
Topics: Adipose Tissue; Aged; Biomarkers; Case-Control Studies; Costa Rica; Dairy Products; Diet; Dietary Fats; Fatty Acids; Female; Humans; Logistic Models; Male; Middle Aged; Motor Activity; Multivariate Analysis; Myocardial Infarction; Obesity; Risk Factors; Surveys and Questionnaires
PubMed: 21549582
DOI: 10.1016/j.numecd.2011.02.003 -
The Biochemical Journal Jan 1957
Topics: Fatty Acids; Food
PubMed: 13403863
DOI: 10.1042/bj0650018 -
American Journal of Physiology.... Jul 2016Classical brown adipocytes such as those found in interscapular brown adipose tissue (iBAT) represent energy-burning cells, which have been postulated to play a pivotal...
Classical brown adipocytes such as those found in interscapular brown adipose tissue (iBAT) represent energy-burning cells, which have been postulated to play a pivotal role in energy metabolism. Brown adipocytes can also be found in white adipose tissue (WAT) depots [e.g., inguinal WAT (iWAT)] following adrenergic stimulation, and they have been referred to as "beige" adipocytes. Whether the presence of these adipocytes, which gives iWAT a beige appearance, can confer a white depot with some thermogenic activity remains to be seen. In consequence, we designed the present study to investigate the metabolic activity of iBAT, iWAT, and epididymal white depots in mice. Mice were either 1) kept at thermoneutrality (30°C), 2) kept at 30°C and treated daily for 14 days with an adrenergic agonist [CL-316,243 (CL)], or 3) housed at 10°C for 14 days. Metabolic activity was assessed using positron emission tomography imaging with fluoro-[(18)F]deoxyglucose (glucose uptake), fluoro-[(18)F]thiaheptadecanoic acid (fatty acid uptake), and [(11)C]acetate (oxidative activity). In each group, substrate uptakes and oxidative activity were measured in anesthetized mice in response to acute CL. Our results revealed iBAT as a major site of metabolic activity, which exhibited enhanced glucose and nonesterified fatty acid uptakes and oxidative activity in response to chronic cold and CL. On the other hand, beige adipose tissue failed to exhibit appreciable increase in oxidative activity in response to chronic cold and CL. Altogether, our results suggest that the contribution of beige fat to acute-CL-induced metabolic activity is low compared with that of iBAT, even after sustained adrenergic stimulation.
Topics: Acetates; Adipose Tissue, Beige; Adipose Tissue, Brown; Adipose Tissue, White; Adrenergic beta-3 Receptor Agonists; Animals; Carbon Radioisotopes; Cold Temperature; Dioxoles; Fatty Acids; Fluorodeoxyglucose F18; Male; Mice; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 27143559
DOI: 10.1152/ajpendo.00545.2015 -
Nutrients Apr 2023Epidemiological studies found that the intake of dairy products is associated with an increased amount of circulating odd-chain fatty acids (OCFA, C15:0 and C17:0) in...
Epidemiological studies found that the intake of dairy products is associated with an increased amount of circulating odd-chain fatty acids (OCFA, C15:0 and C17:0) in humans and further indicate that especially C17:0 is associated with a lower incidence of type 2 diabetes. However, causal relationships are not elucidated. To provide a mechanistic link, mice were fed high-fat (HF) diets supplemented with either milk fat or C17:0 for 20 weeks. Cultured primary mouse hepatocytes were used to distinguish differential effects mediated by C15:0 or C17:0. Despite an induction of OCFA after both dietary interventions, neither long-term milk fat intake nor C17:0 supplementation improved diet-induced hepatic lipid accumulation and insulin resistance in mice. HF feeding with milk fat actually deteriorates liver inflammation. Treatment of primary hepatocytes with C15:0 and C17:0 suppressed JAK2/STAT3 signaling, but only C15:0 enhanced insulin-stimulated phosphorylation of AKT. Overall, the data indicate that the intake of milk fat and C17:0 do not mediate health benefits, whereas C15:0 might be promising in further studies.
Topics: Humans; Animals; Mice; Insulin Resistance; Diabetes Mellitus, Type 2; Fatty Acids; Fatty Liver; Diet, High-Fat
PubMed: 37432205
DOI: 10.3390/nu15092052 -
The American Journal of Clinical... Jun 2014Plasma phospholipid concentrations of trans-palmitoleic acid (trans-16:1n-7), a biomarker of dairy fat intake, are inversely associated with incident type 2 diabetes in... (Observational Study)
Observational Study
BACKGROUND
Plasma phospholipid concentrations of trans-palmitoleic acid (trans-16:1n-7), a biomarker of dairy fat intake, are inversely associated with incident type 2 diabetes in 2 US cohorts.
OBJECTIVE
The objective was to investigate whether the intake of trans-16:1n-7 in particular, or dairy fat in general, is associated with glucose tolerance and key factors determining glucose tolerance.
DESIGN
A cross-sectional investigation was undertaken in 17 men and women with nonalcoholic fatty liver disease and 15 body mass index (BMI)- and age-matched controls. The concentrations of trans-16:1n-7 and 2 other biomarkers of dairy fat intake, 15:0 and 17:0, were measured in plasma phospholipids and free fatty acids (FFAs). Liver fat was estimated by computed tomography-derived liver-spleen ratio. Intravenous-glucose-tolerance tests and oral-glucose-tolerance test (OGTT) and hyperinsulinemic-euglycemic clamps were performed to assess β-cell function and hepatic and systemic insulin sensitivity.
RESULTS
In multivariate analyses adjusted for age, sex, and BMI, phospholipid 17:0, phospholipid trans-16:1n-7, FFA 15:0, and FFA 17:0 were inversely associated with fasting plasma glucose, the area under the curve for glucose during an OGTT, and liver fat. Phospholipid trans-16:1n-7 was also positively associated with hepatic and systemic insulin sensitivity. None of the biomarkers were associated with β-cell function. The associations between dairy fat intake and glucose tolerance were attenuated by adjusting for insulin sensitivity or liver fat, but strengthened by adjusting for β-cell function.
CONCLUSION
Although we cannot rule out reverse causation, these data support the hypothesis that dairy fat improves glucose tolerance, possibly through a mechanism involving improved hepatic and systemic insulin sensitivity and reduced liver fat.
Topics: Adult; Biomarkers; Case-Control Studies; Cohort Studies; Cross-Sectional Studies; Dairy Products; Dietary Fats; Fatty Acids; Fatty Acids, Monounsaturated; Female; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Lipid Metabolism; Liver; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Tomography, X-Ray Computed; Trans Fatty Acids
PubMed: 24740208
DOI: 10.3945/ajcn.113.075457 -
Nutrients May 2019The effect of saturated fatty acids (SFAs) on incident type 2 diabetes (T2D) is controversial and few have systematically appraised the evidence. We conducted a... (Meta-Analysis)
Meta-Analysis
The effect of saturated fatty acids (SFAs) on incident type 2 diabetes (T2D) is controversial and few have systematically appraised the evidence. We conducted a comprehensive search of prospective studies examining these relationships that were published in PubMed, Web of Science, or EMBASE from 21 February 1989 to 21 February 2019. A total of 19 studies were included for systematic review and 10 for meta-analysis. We estimated the summarized relative risk (RR) and 95% confidence interval (95% CI) using a random (if I > 50%) or a fixed effects model (if I ≤ 50%). Although the included studies reported inconclusive results, the majority supported a protective effect of odd-chain and an adverse impact of even-chain SFAs. Meta-analysis showed that the per standard deviation (SD) increase in odd-chain SFAs was associated with a reduced risk of incident T2D (C15:0: 0.86, 0.76-0.98; C17:0: 0.76, 0.59-0.97), while a per SD increase in one even-chain SFA was associated with an increased risk of incident T2D (C14:0: 1.13, 1.09-1.18). No associations were found between other SFAs and incident T2D. In conclusion, our findings suggest an overall protective effect of odd-chain SFAs and the inconclusive impact of even- and very-long-chain SFAs on incident T2D.
Topics: Correlation of Data; Diabetes Mellitus, Type 2; Eicosanoic Acids; Fatty Acids; Humans; Incidence; Myristic Acid; Palmitic Acid; Prospective Studies; Stearic Acids
PubMed: 31052447
DOI: 10.3390/nu11050998