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1.
Role of candidate gene variants in modulating the risk and severity of alcoholic hepatitis.
Beaudoin, JJ, Liang, T, Tang, Q, Banini, BA, Shah, VH, Sanyal, AJ, Chalasani, NP, Gawrieh, S
Alcoholism, clinical and experimental research. 2021;(4):709-719
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Abstract
BACKGROUND Alcoholic hepatitis (AH) is a severe and life-threatening alcohol-associated liver disease. Only a minority of heavy drinkers acquires AH and severity varies among affected individuals, suggesting a genetic basis for the susceptibility to and severity of AH. METHODS A cohort consisting of 211 patients with AH and 176 heavy drinking controls was genotyped for five variants in five candidate genes that have been associated with chronic liver diseases: rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3), rs72613567 in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), rs58542926 in transmembrane 6 superfamily member 2 (TM6SF2), rs641738 in membrane bound O-acyltransferase domain containing 7 (MBOAT7), and a copy number variant in the haptoglobin (HP) gene. We tested the effects of individual variants and the combined/interacting effects of variants on AH risk and severity. RESULTS We found significant associations between AH risk and the risk alleles of rs738409 (p = 0.0081) and HP (p = 0.0371), but not rs72613567 (p = 0.3132), rs58542926 (p = 0.2180), or rs641738 (p = 0.7630), after adjusting for patient's age and sex. A multiple regression model indicated that PNPLA3 rs738409:G [OR = 1.59 (95% CI: 1.15-2.22), p = 0.0055] and HP*2 [OR = 1.38 (95% CI: 1.04-1.82), p = 0.0245], when combined and adjusted for age and sex also had a large influence on AH risk among heavy drinkers. In the entire cohort, variants in PNPLA3 and HP were associated with increased total bilirubin and Model for End-stage Liver Disease (MELD) score, both measures of AH severity. The HSD17B13 rs72613567:AA allele was not found to reduce risk of AH in patients carrying the G allele of PNPLA3 rs738409 (p = 0.0921). CONCLUSION PNPLA3 and HP genetic variants increase AH risk and are associated with total bilirubin and MELD score, surrogates of AH severity.
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Metabolic liver disease - what's in a name?
Herman, MA
Nature reviews. Endocrinology. 2021;(2):79-80
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Lipozyme 435-Mediated Synthesis of Xylose Oleate in Methyl Ethyl Ketone.
Gonçalves, MCP, Amaral, JC, Fernandez-Lafuente, R, Sousa Junior, R, Tardioli, PW
Molecules (Basel, Switzerland). 2021;(11)
Abstract
In this paper, we have performed the Lipozyme 435-catalyzed synthesis of xylose oleate in methyl ethyl ketone (MEK) from xylose and oleic acid. The effects of substrates' molar ratios, reaction temperature, reaction time on esterification rates, and Lipozyme 435 reuse were studied. Results showed that an excess of oleic acid (xylose: oleic acid molar ratio of 1:5) significantly favored the reaction, yielding 98% of xylose conversion and 31% oleic acid conversion after 24 h-reaction (mainly to xylose mono- and dioleate, as confirmed by mass spectrometry). The highest Lipozyme 435 activities occurred between 55 and 70 °C. The predicted Ping Pong Bi Bi kinetic model fitted very well to the experimental data and there was no evidence of inhibitions in the range assessed. The reaction product was purified and presented an emulsion capacity close to that of a commercial sugar ester detergent. Finally, the repeated use of Lipozyme 435 showed a reduction in the reaction yields (by 48 and 19% in the xylose and oleic acid conversions, respectively), after ten 12 h-cycles.
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The rs738409 G Allele in PNPLA3 Is Associated With a Reduced Risk of COVID-19 Mortality and Hospitalization.
Innes, H, Buch, S, Barnes, E, Hampe, J, Marjot, T, Stickel, F
Gastroenterology. 2021;(7):2599-2601.e2
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Continuous production of monoacylglycerol via glycerolysis of babassu oil by immobilized Burkholderia cepacia lipase in a packed bed reactor.
Vilas Bôas, RN, Lima, R, Silva, MVC, Freitas, L, Aguiar, LG, de Castro, HF
Bioprocess and biosystems engineering. 2021;(10):2205-2215
Abstract
This study investigated the glycerolysis of babassu oil by Burkholderia cepacia lipase immobilized on SiO2-PVA particles in a continuous packed bed reactor. Experiments were conducted in a solvent-free system at 273.15 K either in an inert atmosphere or in the presence of cocoa butter to prevent lipid oxidation. The reactor (15 × 55 mm) was run at a fixed space time of 9.8 h using different molar ratios of babassu oil to glycerol (1:3, 1:6, 1:9, 1:12, and 1:15) to assess the effects of reactant molar ratio on monoacylglycerol productivity and selectivity. Nitrogen atmosphere and cocoa butter were equally effective in inhibiting lipid oxidation, indicating that addition of cocoa butter to glycerolysis reactions may be an interesting cost-reduction strategy. An oil/glycerol molar ratio of 1:9 resulted in the highest productivity (52.3 ± 2.9 mg g-1 h-1) and selectivity (31.5 ± 1.8%). Residence time distribution data were fitted to an axial dispersion model for closed-vessel boundary conditions, giving a mass transfer coefficient (kc) of 3.4229 × 10-6 m s-1. A kinetic model based on elementary steps of the studied reaction was written in Scilab and compared with experimental data, providing standard deviations in the range of 5.5-7.5%.
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Thermo-alkali-stable lipase from a novel Aspergillus niger: statistical optimization, enzyme purification, immobilization and its application in biodiesel production.
El-Ghonemy, DH, Ali, TH, Hassanein, NM, Abdellah, EM, Fadel, M, Awad, GEA, Abdou, DAM
Preparative biochemistry & biotechnology. 2021;(3):225-240
Abstract
The influences of nutritional components affecting lipase production from the new Aspergillus niger using wheat bran as substrate were studied by employing Plackett-Burman and central composite statistical designs. Out of the 11 medium components tested, sucrose, KH2PO4 and MgSO4 at final concentrations of 3.0, 1.0 and 0.5 g/L, respectively, were reported to contribute positively to enzyme production (20.09 ± 0.98 U/g ds). The enzyme was purified through ammonium sulfate precipitation followed by Sephadex G-100 gel filtration. Molecular mass of the purified lipase was 57 kDa as evident on SDS-PAGE. Different methods of immobilization were studied and the highest immobilization yield of 81.7 ± 2.18% was reported with agarose (2%) and the optimum temperature was raised from 45 to 50 °C. Immobilized lipase could retain 80% of its original activity at 60 °C after 1 hr of incubation, and was stable at pH values between neutral and alkaline pH. Lipase-catalyzed transesterification process of fungal oil resulted in a fatty acid methyl ester yield consisting of a high percentage of polyunsaturated fatty acids (83.6%), making it appropriate to be used as winter-grade biodiesel. The operational stability studies revealed that the immobilized lipase could keep 70% of its total activity after 5 cycles of the transesterification process.
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Dietary fat content and adipose triglyceride lipase and hormone-sensitive lipase gene expressions in adults' subcutaneous and visceral fat tissues.
Zareie, R, Yuzbashian, E, Rahimi, H, Asghari, G, Zarkesh, M, Hedayati, M, Djazayery, A, Movahedi, A, Mirmiran, P, Khalaj, A
Prostaglandins, leukotrienes, and essential fatty acids. 2021;:102244
Abstract
INTRODUCTION We examined the association of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) gene expressions, as the key regulators of lipolysis, with dietary fat quantity and composition in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). METHODS In this observational study, samples were collected from patients undergoing elective abdominal surgery. Participants were categorized into two groups based on their body mass index (BMI) status. Dietary, anthropometric, and biochemical data were collected before surgery. Linear regression was performed to determine the association of dietary fat content with ATGL and HSL gene expressions in SAT and VAT. RESULTS 152 individuals with a mean ± SD age of 40.7 ± 13.2 years and a median (inter-quartile range) BMI of 39.4 (26.5-45.3 kg/m2) participated in this study, of whom 54 were non-obese (BMI<30 kg/m2), and 98 were obese (BMI≥30 kg/m2). Among non-obese participants, positive associations were observed between ATGL mRNA expression and reported intakes of total fatty acids (TFA) (β=0.306, P = 0.025), myristic (β=0.285, P = 0.038), palmitic (β=0.417, P = 0.002), oleic (β=0.333, P = 0.017), dairy trans (β=0.374, P = 0.006), and other trans FAs (β=0.369, P = 0.006) in SAT. In contrast, inverse associations between HSL mRNA expression and reported intakes of TFAs (β=-0.377, P = 0.005), myristic (β=-0.282, P = 0.039), palmitic (β=-0.372, P = 0.006), stearic (β=-0.314, P = 0.020), and oleic acid (β=-0.372, P = 0.007) were observed in SAT. No associations were observed among obese participants, nor in VAT among non-obese individuals. CONCLUSION ATGL and HSL mRNA expressions in SAT were associated with dietary fat quantity and composition among non-obese adults.
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Impact of the Association Between PNPLA3 Genetic Variation and Dietary Intake on the Risk of Significant Fibrosis in Patients With NAFLD.
Vilar-Gomez, E, Pirola, CJ, Sookoian, S, Wilson, LA, Belt, P, Liang, T, Liu, W, Chalasani, N
The American journal of gastroenterology. 2021;(5):994-1006
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Abstract
INTRODUCTION This study explored the relationship between patatin-like phospholipase domain-containing 3 gene (PNPLA3 rs738409), nutrient intake, and liver histology severity in patients with nonalcoholic fatty liver disease (NAFLD). METHODS PNPLA3-rs738409 variant was genotyped in 452 non-Hispanic whites with histologically confirmed NAFLD who completed Food Frequency Questionnaire within 6 months of their liver biopsy. The fibrosis severity on liver histology was the outcome of interest. RESULTS The distribution of PNPLA3 genotypes was CC: 28%, CG: 46%, and GG: 25%. High-carbohydrate (% of energy/d) intake was positively associated (adjusted [Adj] odds ratio [OR]: 1.03, P < 0.01), whereas higher n-3 polyunsaturated fatty acids (n-3 PUFAs) (g/d) (Adj. OR: 0.17, P < 0.01), isoflavones (mg/d) (Adj. OR: 0.74, P = 0.049), methionine (mg/d) (Adj. OR: 0.32, P < 0.01), and choline (mg/d) (Adj. OR: 0.32, P < 0.01) intakes were inversely associated with increased risk of significant fibrosis (stage of fibrosis ≥2). By using an additive model of inheritance, our moderation analysis showed that PNPLA3 rs738409 significantly modulates the relationship between carbohydrate (%), n-3 PUFAs, total isoflavones, methionine, and choline intakes and fibrosis severity in a dose-dependent, genotype manner. These dietary factors tended to have a larger and significant effect on fibrosis severity among rs738409 G-allele carriers. Associations between significant fibrosis and carbohydrates (Adj. OR: 1.04, P = 0.019), n-3 PUFAs (Adj. OR: 0.16, P < 0.01), isoflavones (Adj. OR: 0.65, P = 0.025), methionine (Adj. OR: 0.30, P < 0.01), and total choline (Adj. OR: 0.29, P < 0.01) intakes remained significant only among rs738409 G-allele carriers. DISCUSSION This gene-diet interaction study suggests that PNPLA3 rs738409 G-allele might modulate the effect of specific dietary nutrients on risk of fibrosis in patients with NAFLD.
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Skin Commensal Fungus Malassezia and Its Lipases.
Park, M, Park, S, Jung, WH
Journal of microbiology and biotechnology. 2021;(5):637-644
Abstract
Malassezia is the most abundant genus in the fungal microflora found on human skin, and it is associated with various skin diseases. Among the 18 different species of Malassezia that have been identified to date, M. restricta and M. globosa are the most predominant fungal species found on human skin. Several studies have suggested a possible link between Malassezia and skin disorders. However, our knowledge on the physiology and pathogenesis of Malassezia in human body is still limited. Malassezia is unable to synthesize fatty acids; hence, it uptakes external fatty acids as a nutrient source for survival, a characteristic compensated by the secretion of lipases and degradation of sebum to produce and uptake external fatty acids. Although it has been reported that the activity of secreted lipases may contribute to pathogenesis of Malassezia, majority of the data were indirect evidences; therefore, enzymes' role in the pathogenesis of Malassezia infections is still largely unknown. This review focuses on the recent advances on Malassezia in the context of an emerging interest for lipases and summarizes the existing knowledge on Malassezia, diseases associated with the fungus, and the role of the reported lipases in its physiology and pathogenesis.
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Mechanoenzymatic Transformations in the Absence of Bulk Water: A More Natural Way of Using Enzymes.
Kaabel, S, Friščić, T, Auclair, K
Chembiochem : a European journal of chemical biology. 2020;(6):742-758
Abstract
Mechanochemical enzymatic reactions without bulk water have emerged as a low-waste and efficient method to access useful chemicals and to depolymerize biomass components in a single step. This emergent mechanoenzymatic reaction strategy is able to take advantage of the stereospecificity, regio- and stereoselectivity, as well as renewability of enzymes, while avoiding bulk solvents, offering the opportunity to control the direction of the reaction, bypassing reactant solubility issues, and enabling reactions with water-sensitive substrates or products. Enzymes are traditionally used in dilute aqueous solution, which is quite different from their crowded, water-depleted natural environment. This review outlines recent work which demonstrates that enzymes can be equally or even more efficient under mechanochemical conditions, without bulk aqueous or organic solvent.