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Environment International Dec 20192,2',4,4'-Tetrabromodiphenyl ether (BDE-47), a predominant polybrominated diphenyl ether (PBDE), has received extensive attention for its potential environmental impact....
2,2',4,4'-Tetrabromodiphenyl ether (BDE-47), a predominant polybrominated diphenyl ether (PBDE), has received extensive attention for its potential environmental impact. An integrated study of metabolomics and transcriptomics was conducted on two rice (Oryza sativa) cultivars, Lianjing-7 (LJ-7) and Yongyou-9 (YY-9), which have been identified as tolerant and sensitive cultivars to BDE-47, respectively. The objective was to investigate the molecular mechanisms of their different ability to tolerate BDE-47. Both rice plants were cultivated to maturity in soils containing three concentrations of BDE-47 (10, 20, and 50 mg/kg). Metabolomic analyses of rice grains identified 65 metabolites in LJ-7 and 45 metabolites in YY-9, including amino acids, saccharides, organic acids, fatty acids, and secondary metabolites. In the tolerant cultivar LJ-7 exposed to 50 mg/kg BDE-47, concentrations of most of the metabolites increased significantly, with α-ketoglutaric acid increased by 20-fold and stigmastanol increased by 12-fold. In the sensitive cultivar YY-9, the concentrations of most metabolites increased after the plant was exposed to 1 and 10 mg/kg BDE-47 but decreased after the plant was exposed to 50 mg/kg BDE-47. Transcriptomic data demonstrated that regulation of gene expressions was affected most in LJ-7 exposed to 50 mg/kg BDE-47 (966 genes up-regulated and 620 genes down-regulated) and in YY-9 exposed to 10 mg/kg BDE-47 (85 genes up-regulated and 291 genes down-regulated), in good accordance with the observed metabolic alternation in the two cultivars. Analyses of metabolic pathways and KEGG enrichment revealed that many biological processes, including energy consumption and biosynthesis, were perturbed in the two rice cultivars by BDE-47. A majority of metabolites and genes involved in dominating pathways of energy consumption (e.g., tricarboxylic acid cycle) and the biosynthesis (e.g., metabolism of saccharides and amino acids) were enhanced in LJ-7 by BDE-47. In contrast, energy consumption was increased while biosynthetic processes were inhibited in YY-9 by BDE-47, which could lead to the sensitivity of YY-9 to BDE-47. The combined results suggest that the different defensive abilities of these two rice cultivars in response to BDE-47 could be attributed to their differences in energy-consumption strategy and biosynthesis of nutritional components in grains. This study provides a useful reference for rice cultivation in PBDE-polluted areas.
Topics: Environmental Pollutants; Gene Expression Regulation, Plant; Halogenated Diphenyl Ethers; Metabolomics; Oryza; Seeds; Soil; Transcriptome
PubMed: 31521816
DOI: 10.1016/j.envint.2019.105154 -
European Journal of Nutrition Aug 2020Lowering of LDL cholesterol levels by plant sterols and stanols is associated with decreased risk of cardiovascular disease in humans. Plant sterols and stanols also...
PURPOSE
Lowering of LDL cholesterol levels by plant sterols and stanols is associated with decreased risk of cardiovascular disease in humans. Plant sterols and stanols also lower triacylglycerol (TG). However, it is not fully understood how reduction in TG is achieved and what the full potential of plant sterols and stanols is on whole-body metabolism. We here hypothesize that high levels of plant sterols and stanols stimulate whole-body energy expenditure, which can be attributed to changes in mitochondrial function of brown adipose tissue (BAT), skeletal muscle and liver.
METHODS
Phytosterolemic mice were fed chow diets for 32 weeks to examine whole-body weight gain. In vitro, 24-h incubation were performed in adipocytes derived from human BAT, human myotubes or HepG2 human hepatocytes using sitosterol or sitostanol. Following mitochondrial function was assessed using seahorse bioanalyzer.
RESULTS
Chow feeding in phytosterolemic mice resulted in diminished increase in body weight compared to control mice. In vitro, sitosterol or sitostanol did not change mitochondrial function in adipocytes derived from human BAT or in cultured human myotubes. Interestingly, maximal mitochondrial function in HepG2 human hepatocytes was decreased following sitosterol or sitostanol incubation, however, only when mitochondrial function was assessed in low glucose-containing medium.
CONCLUSIONS
Beneficial in vivo effects of plant sterols and stanols on lipid and lipoprotein metabolism are well recognized. Our results indicate that alterations in human mitochondrial function are apparently not involved to explain these beneficial effects.
Topics: Adipocytes, Brown; Animals; Hepatocytes; Humans; Mice; Mitochondria; Muscle Fibers, Skeletal; Phytosterols; Respiration; Sitosterols
PubMed: 31317217
DOI: 10.1007/s00394-019-02052-y -
BioMed Research International 2019L. (Rubiaceae) is a climber which is widely distributed in Asian countries including Malaysia. The plant is traditionally used to treat various diseases including...
L. (Rubiaceae) is a climber which is widely distributed in Asian countries including Malaysia. The plant is traditionally used to treat various diseases including diabetes. This study is to evaluate the enzymatic inhibition activity of twigs extracts and to identify the metabolites responsible for the bioactivity by gas chromatography-mass spectrometry (GC-MS) metabolomics profiling. Three different twig extracts, namely, hexane (PFH), chloroform (PFC), and methanol (PFM), were submerged for their -amylase and -glucosidase inhibition potential in 5 replicates for each. Results obtained from the loading column scatter plot of orthogonal partial least square (OPLS) model revealed the presence of 12 bioactive compounds, namely, dl--tocopherol, n-hexadecanoic acid, 2-hexyl-1-decanol, stigmastanol, 2-nonadecanone, cholest-8(14)-en-3-ol, 4,4-dimethyl-, (3,5)-, stigmast-4-en-3-one, stigmasterol, 1-ethyl-1-tetradecyloxy-1-silacyclohexane, ɣ-sitosterol, stigmast-7-en-3-ol, (3,5,24S)-, and -monostearin. molecular docking was carried out using the crystal structure -amylase (PDB ID: 4W93) and -glucosidase (PDB ID: 3WY1). -Amylase-n-hexadecanoic acid exhibited the lowest binding energy of -2.28 kcal/mol with two hydrogen bonds residue, namely, LYS178 and TYR174, along with hydrophobic interactions involving PRO140, TRP134, SER132, ASP135, and LYS172. The binding interactions of -glucosidase-n-hexadecanoic acid complex ligand also showed the lowest binding energy among 5 major compounds with the energy value of -4.04 kcal/mol. The complex consists of one hydrogen bond interacting residue, ARG437, and hydrophobic interactions with ALA444, ASP141, GLN438, GLU432, GLY374, LEU373, LEU433, LYS352, PRO347, THR445, HIS348, and PRO351. The study provides informative data on the potential antidiabetic inhibitors identified in twigs, indicating the plant has the therapeutic effect properties to manage diabetes.
Topics: Data Analysis; Gas Chromatography-Mass Spectrometry; Hypoglycemic Agents; Inhibitory Concentration 50; Least-Squares Analysis; Metabolome; Metabolomics; Molecular Docking Simulation; Multivariate Analysis; Plant Extracts; Principal Component Analysis; Rubiaceae; alpha-Amylases; alpha-Glucosidases
PubMed: 31275982
DOI: 10.1155/2019/7603125 -
Environmental Pollution (Barking, Essex... Jan 2019Sewage pollution is a principal factor of decreasing water quality, although it has not been considered a real impact in Amazonia that is still considered a pristine...
Sewage pollution is a principal factor of decreasing water quality, although it has not been considered a real impact in Amazonia that is still considered a pristine environment around the world. Thus, this study aimed to assess the levels of sewage contamination in sediments from three streams crossing Manaus - a Brazilian city of 2,403,796 inhabitants in the heart of the Amazon rain forest. Cholesterol, cholestanol, brassicasterol, ergosterol, stigmasterol, β-sitosterol, campesterol, stigmastanol, coprostanol, and epicoprostanol levels were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS). The fecal indicator, coprostanol, was found in high concentrations (509-12 830 ng g) and high relative proportions (21-54%) in all samples collected in the Mindu stream that crosses many heavily populated districts of the city, and in the Quarenta stream that crosses the Industrial District of Manaus. The sediments of the Tarumã-Açu stream also presented coprostanol; however, concentrations (
Topics: Biomarkers; Brazil; Cholestadienols; Cholestanol; Cholestanols; Cholesterol; Chromatography, Liquid; Drug Contamination; Environmental Monitoring; Feces; Geologic Sediments; Phytosterols; Rivers; Sewage; Sitosterols; Sterols; Tandem Mass Spectrometry; Water Pollutants; Water Pollution; Water Quality
PubMed: 30390455
DOI: 10.1016/j.envpol.2018.10.055 -
Bioscience Reports Oct 2018This short article provides a comment on the recent article by Tauriainen et al. [ (2018) , BSR20171274 https://doi.org/10.1042/BSR20171274].
This short article provides a comment on the recent article by Tauriainen et al. [ (2018) , BSR20171274 https://doi.org/10.1042/BSR20171274].
Topics: Bile; Humans; Liver; Non-alcoholic Fatty Liver Disease; Obesity; Sitosterols
PubMed: 30287500
DOI: 10.1042/BSR20180505 -
Analytical Chemistry Jul 2018There has been an increasing interest during recent years in the role of the gut microbiome on health and disease. Therefore, metabolites in human feces related to...
There has been an increasing interest during recent years in the role of the gut microbiome on health and disease. Therefore, metabolites in human feces related to microbial activity are attractive surrogate marker to track changes of microbiota induced by diet or disease. Such markers include 5α/β-stanols as microbiome-derived metabolites of sterols. Currently, reliable, robust, and fast methods to quantify fecal sterols and their related metabolites are missing. We developed a liquid chromatography-high-resolution mass spectrometry (LC-MS/HRMS) method for the quantification of sterols and their 5α/β-stanols in human fecal samples. Fecal sterols were extracted and derivatized to N, N-dimethylglycine esters. The method includes cholesterol, coprostanol, cholestanol and sitosterol, 5α/β-sitostanol, campesterol and 5α/β-campestanol. Application of a biphenyl column permits separation of isomeric 5α- and 5β-stanols. Sterols are detected in parallel reaction monitoring (PRM) mode and stanols in full scan mode. HRMS allows differentiation of isobaric β-stanols and the [M + 2] isotope peak of the coeluting sterol. Performance characteristics meet the criteria recommended by Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. Analysis of fecal samples from healthy volunteers revealed high interindividual variability of sterol and stanol fractions. Interestingly, cholesterol and sitosterol showed similar fractions of mainly 5β-stanols. In contrast, campesterol is substantially converted to 5α-campestanol and might be a poorer substrate for bacterial metabolism. Robust and fast quantification of fecal sterols and their related stanols by LC-MS/HRMS offers great potential to find novel microbiome-related biomarker in large-scale studies.
Topics: Cholesterol; Chromatography, Liquid; Feces; Gastrointestinal Microbiome; Humans; Limit of Detection; Phytosterols; Sitosterols; Sterols; Tandem Mass Spectrometry
PubMed: 29920210
DOI: 10.1021/acs.analchem.8b01278 -
Food Chemistry Sep 2018The esters of β-sitostanol and fatty acids are known for their effect as cholesterol-lowering agents. In this work, the efficiency of three lipases as biocatalysts of...
The esters of β-sitostanol and fatty acids are known for their effect as cholesterol-lowering agents. In this work, the efficiency of three lipases as biocatalysts of the esterification of β-sitostanol and C16 and C18 fatty acids was compared. The sterol esterase of Ophiostoma piceae (OPEr) yielded the highest esterification rates and was selected for further optimization of the reaction. The effects of four parameters (temperature, enzymatic dosage, acyl donor concentration, and reaction time) on ester synthesis were investigated and the process conditions were optimized using response surface methodology (RSM). The best conditions for esterification for each fatty acid were predicted using a second-order model, and experimentally validated. Very high esterification efficiencies (86-97%) were observed using the predicted values for the four variables. This approach was shown to be suitable for optimizing the enzymatic production of β-sitostanol esters, which represents a green alternative to the chemical synthesis of these dietary complements.
Topics: Biocatalysis; Chemistry Techniques, Synthetic; Esterification; Esters; Lipase; Ophiostoma; Sitosterols
PubMed: 29739574
DOI: 10.1016/j.foodchem.2018.04.031 -
Proceedings. Biological Sciences Apr 2018With the expansion of urban centres in the mid-twentieth century and the post-1970 decrease in pesticides, populations of double-crested cormorants () and ring-billed...
With the expansion of urban centres in the mid-twentieth century and the post-1970 decrease in pesticides, populations of double-crested cormorants () and ring-billed gulls () around Lake Ontario (Canada and USA) have rapidly rebounded, possibly to unprecedented numbers. Along with the use of traditional palaeolimnological methods (e.g. stable isotopes, biological proxies), we now have the capacity to develop specific markers for directly tracking the presence of waterbirds on nesting islands. Here, we apply the use of lipophilic sterols and stanols from both plant and animal-faecal origins as a reliable technique, independent of traditional isotopic methods, for pinpointing waterbird arrival and population growth over decadal timescales. Sterol and stanol concentrations measured in the guano samples of waterbird species were highly variable within a species and between the three species of waterbirds examined. However, cholesterol was the dominant sterol in guano, and phytosterols were also high in ring-billed gull guano. This variability highlights a specialist piscivorous diet for cormorants compared to a generalist, omnivorous diet for gulls, which may now often include grain and invertebrates from agricultural fields. A ratio that includes cholesterol and sitosterol plus their aerobically reduced products (cholestanol, stigmastanol) best explained the present range of bird abundance across the islands and was significantly correlated to sedimentary δN. Overall, we demonstrate the use of sterols and stanols as a direct means for tracking the spatial and temporal presence of waterbirds on islands across Lake Ontario, and probably elsewhere.
Topics: Animals; Biomarkers; Birds; Charadriiformes; Diet; Environmental Biomarkers; Environmental Monitoring; Hydrogenation; New York; Ontario; Oxidation-Reduction; Population Dynamics; Sterols
PubMed: 29695442
DOI: 10.1098/rspb.2018.0631 -
Bioscience Reports Apr 2018: Non-alcoholic fatty liver disease (NAFLD) associates with low levels of serum plant sterols in cross-sectional studies. In addition, it has been suggested that the... (Clinical Trial)
Clinical Trial
: Non-alcoholic fatty liver disease (NAFLD) associates with low levels of serum plant sterols in cross-sectional studies. In addition, it has been suggested that the hepatic sterol transport mechanisms are altered in NAFLD. Therefore, we investigated the association between serum, liver and bile plant sterols and sitostanol with NAFLD.: Out of the 138 individuals (age: 46.3 ± 8.9, body mass index: 43.3 ± 6.9 kg/m², 28% men and 72% women), 44 could be histologically categorized to have normal liver, and 94 to have NAFLD. Within the NAFLD group, 28 had simple steatosis and 27 had non-alcoholic steatohepatitis. Plant sterols and sitostanol were measured from serum (=138), liver (=38), and bile (=41). The expression of genes regulating liver sterol metabolism and inflammation was measured (=102).: Liver and bile sitostanol ratios to cholesterol were higher in those with NAFLD compared to those with histologically normal liver (all <0.022). Furthermore, liver sitostanol to cholesterol ratio correlated positively with histological steatosis and lobular inflammation ( > 0.407, <0.01 for both). In contrast, liver sitosterol to cholesterol ratio correlated negatively with steatosis ( = -0.392, =0.015) and lobular inflammation ( = -0.395, =0.014). Transcriptomics analysis revealed suggestive correlations between serum plant sterol levels and mRNA expression.: Our study showed that liver and bile sitostanol ratios to cholesterol associated positively and liver sitosterol ratio to cholesterol associated negatively with liver steatosis and inflammation in obese individuals with NAFLD..
Topics: Adult; Bile; Female; Humans; Liver; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Sitosterols
PubMed: 29540533
DOI: 10.1042/BSR20171274 -
The Journal of Pediatrics Sep 2017To assess the association between biomarkers of thyroid status and 5α-stanols in patients with sitosterolemia treated with ezetimibe (EZE). (Clinical Trial)
Clinical Trial
OBJECTIVES
To assess the association between biomarkers of thyroid status and 5α-stanols in patients with sitosterolemia treated with ezetimibe (EZE).
STUDY DESIGN
Eight patients with sitosterolemia (16-56 years of age) were studied during 14 weeks off EZE therapy and 14 weeks on EZE (10 mg/day). Serum thyroid biomarkers (free triiodothyronine [FT3], free thyroxine [FT4], FT3/FT4 ratio, thyroid-stimulating hormone), 5α-stanols (sitostanol and cholestanol), and cholestanol precursors (total cholesterol and its synthesis marker lathosterol, and 7α-hydroxy-4-cholesten-3-one cholestenol) were measured at baseline and during the 14 weeks off EZE and on EZE.
RESULTS
EZE increased FT3/FT4 (10% ± 4%; P = .02). EZE reduced plasma and red blood cells sitostanol (-38% ± 6% and -20% ± 4%; all P < .05) and cholestanol (-18% ± 6% and -13% ± 3%; all P < .05). The change in plasma cholestanol level on EZE inversely correlated with the change in FT3/FT4 (r = -0.86; P = .01). EZE lowered total cholesterol (P < .0001) and did not affect 7α-hydroxy-4-cholesten-3-one cholestanol. EZE increased (P < .0001) lathosterol initially, but the level was not sustained, resulting in similar levels at week 14 off EZE and on EZE.
CONCLUSION
In patients with STSL, 5α-stanols levels might be associated with thyroid function. EZE reduces circulating 5α-stanols while increasing FT3/FT4, implying increased conversion of T4 to T3, thus possibly improving thyroid hormone status.
TRIAL REGISTRATION
ClinicalTrials.govNCT01584206.
Topics: Adolescent; Adult; Anticholesteremic Agents; Cholestanol; Cholestenones; Cholesterol; Ezetimibe; Female; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Male; Middle Aged; Phytosterols; Sitosterols; Thyrotropin; Thyroxine; Triiodothyronine; Young Adult
PubMed: 28625503
DOI: 10.1016/j.jpeds.2017.05.049