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1.
Four-Week Omega-3 Supplementation in Carriers of the Prosteatotic PNPLA3 p.I148M Genetic Variant: An Open-Label Study.
Kuttner, CS, Mancina, R, Wagenpfeil, G, Lammert, F, Stokes, CS
Lifestyle genomics. 2019;(1-6):10-17
Abstract
BACKGROUND/AIMS: The PNPLA3 loss-of-function variant p.I148M is a strong genetic determinant of nonalcoholic fatty liver disease. The PNPLA3 protein functions as an intracellular lipase in the liver, with a greater activity on unsaturated fatty acids. This study aimed to determine whether short-term supplementation with omega-3 fatty acids impacts hepatic steatosis differently in PNPLA3 p.148I wild-type individuals as compared to homozygous carriers of the PNPLA3 p.148M variant. METHODS Twenty subjects with hepatic steatosis (50% women, age 18-77 years) were included. Ten subjects homozygous for the PNPLA3 148M variant were matched to 10 wild-type individuals. The subjects received 4 g omega-3 fatty acids (1,840 mg eicosapentaenoic acid and 1,520 mg docosahexaenoic acid) a day for 4 weeks. Transient elastography with a controlled attenuation parameter (CAP) was used to quantify liver fat before and after the intervention. Body composition, fibrosis, liver function tests, serum free fatty acids (FFA) and glucose markers were compared. RESULTS Patients homozygous for the PNPLA3 p.148M variant (risk group) demonstrated no significant changes in CAP compared to baseline (284 ± 55 vs. 287 ± 65 dB/m) as did the control group (256 ± 56 vs. 262 ± 55 dB/m). While serum liver enzyme activities remained unchanged in both groups, the risk group displayed significantly (p = 0.02) lower baseline FFA concentrations (334.5 [range 281.0-431.0] vs. 564.5 [range 509.0-682.0] μmol/L), which markedly increased by 9.1% after the intervention. In contrast, FFA concentrations decreased significantly (p = 0.01) by 28.3% in the wild-type group. CONCLUSIONS Short-term omega-3 fatty acid supplementation did not significantly alter hepatic steatosis. The nutrigenomic and metabolic effects of omega-3 fatty acids should be investigated further in carriers of the PNPLA3 148M risk variant.
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2.
Nonalcoholic Fatty Liver Disease and Metabolic Syndrome.
Kim, D, Touros, A, Kim, WR
Clinics in liver disease. 2018;(1):133-140
Abstract
Nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are highly prevalent, affecting approximately one-third of the US population. The relationship between NAFLD and MS is complex and may be bidirectionally associated. NAFLD is strongly associated with MS, the components of which include abdominal obesity, hyperglycemia, hypertension, and dyslipidemia. NAFLD associated with certain genetic factors such as the PNPLA3 G allele variant is not accompanied by insulin resistance and MS. Lifestyle modification, including diet and physical activity targeting visceral adiposity, remains the standard of care for patients with NAFLD and MS.
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3.
The Genetics of Pediatric Nonalcoholic Fatty Liver Disease.
Goyal, NP, Schwimmer, JB
Clinics in liver disease. 2018;(1):59-71
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. Severe fibrosis and cirrhosis are potential consequences of pediatric NAFLD and can occur within a few years of diagnosis. Observations suggest that genetics may be a strong modifying factor in the presentation, severity, and natural history of the disease. There is increasing interest in determining at-risk populations based on genetics in the hope of finding genotypes that correlate to NAFLD phenotype. Ultimately, the hope is to be able to tailor therapeutics to genetic predispositions and decrease disease morbidity in children with NAFLD.
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4.
Neutrophil-lymphocyte ratio, gamma-glutamyl transpeptidase, lipase, high-density lipoprotein as a panel of factors to predict acute pancreatitis in pregnancy.
Zhang, L, Wang, Y, Han, J, Shen, H, Zhao, M, Cai, S
Medicine. 2018;(26):e11189
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Abstract
Acute pancreatitis in pregnancy (APIP) is a rare but dangerous complication. APIP has common symptoms with acute abdomen. Assessment of an acute abdomen is more complicated during pregnancy because the gravid uterus could mask most of symptomatic signs. It has been a challenge to diagnose APIP by physical examination or diagnostic imaging. Case studies on APIP are also limited for analysis on the risk factors associated with the disease. This retrospective study evaluated a series of risk factors from a relatively substantial number of APIP cases to determine early predictors or prognosis markers for APIP.Fifty-nine APIP patients together with 179 random normal pregnant women in Shengjing Affiliated Hospital of China Medical University were included for this retrospective study. Medical parameters of blood test in biochemistry and hematology were compared between 2 groups using t test. Multivariate logistic regression analysis was performed to investigate the relationship between various factors and APIP using Statistical Applied Software (SAS student version).Compared with normal pregnant women, APIP patients have elevated values in alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen, creatinine, C-reactive protein, direct bilirubin, fibrin degradation products, gamma-glutamyl transpeptidase (GGT), glucose, lipase, pH and decreased values in albumin, fibrinogen, high-density lipoprotein (HDL), hemoglobin, low-density lipoprotein cholesterol (LDL-D), and total proteins from their blood tests. In addition, APIP patients have decreased numbers in red cells but increased numbers in white blood cells and increased ratio of neutrophil/lymphocyte (N/L). Among these factors, N/LR, GGT, lipase, and HDL are significantly associated with APIP. This study suggests that the combination of those factors serve as a panel of indicators for early-onset prognosis of APIP.GGT, lipase, HDL, and N/LR can serve as a panel of factors to predict APIP. More case studies are important to further evaluate the predicting power of this panel factors in APIP.
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Donor PNPLA3 rs738409 genotype is a risk factor for graft steatosis. A post-transplant biopsy-based study.
Trunečka, P, Míková, I, Dlouhá, D, Hubáček, JA, Honsová, E, Kolesár, L, Lánská, V, Fraňková, S, Šperl, J, Jirsa, M, et al
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2018;(5):490-495
Abstract
BACKGROUND & AIMS The rs738409 c.444C > G (p.I148M) polymorphism in PNPLA3 is a major factor predisposing to non-alcoholic fatty liver disease. The aim of the study was to clarify the impact of liver and extrahepatic expression of the PNPLA3 p.148M variant on liver graft steatosis after liver transplantation. METHODS Fat content was assessed in liver biopsies from 176 transplant recipients. During a period of 4 ± 1 years after transplantation, 17 patients developed grade 3 steatosis, 14 patients grade 2 steatosis, 56 patients grade 1 steatosis, and 89 patients grade 0 steatosis. The influence of the recipient and donor rs738409 genotype and clinical and laboratory data on liver fat content were analyzed using ordinal logistic regression. RESULTS The PNPLA3 rs738409 CC/CG/GG genotype frequencies, respectively, were 0.494/0.449/0.057 in the graft donors and 0.545/0.330/0.125 in the graft recipients. In the multivariate analysis, the presence of the PNPLA3 c.444G allele in donor (OR 1.62; 95%CI 1.12-2.33), post-transplant BMI (OR 1.14; 95%CI 1.07-1.22), diabetes mellitus (OR 1.99; 95%CI 1.22-3.22), and serum triglycerides (OR 1.40; 95%CI 1.11-1.76) were independent risk factors for increased liver graft fat content. CONCLUSIONS These data indicate that the liver expression of the PNPLA3 p.148M variant confers a genetic predisposition to liver graft steatosis along with nutritional status and diabetes.
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Study of Family Clustering and PNPLA3 Gene Polymorphism in Pediatric Non Alcoholic Fatty Liver Disease.
Sood, V, Khanna, R, Rawat, D, Sharma, S, Alam, S, Sarin, SK
Indian pediatrics. 2018;(7):561-567
Abstract
OBJECTIVE To find association of pediatric NAFLD with metabolic risk factors, and Patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene polymorphism. DESIGN Cross-sectional study. SETTING Pediatric Hepatology unit of a tertiary care hospital. PARTICIPANTS Overweight/obese children (<18 years) with (69 patients) or without (30 patients) NAFLD (ultrasonography based), and their parents. INTERVENTION Metabolic screening, PNPLA3 gene polymorphism, and transient elastography. OUTCOME MEASURE Association of pediatric NAFLD with parental metabolic risk factors and PNPLA3 gene polymorphism. RESULTS In the NAFLD group, there was high parental incidence of metabolic diseases, fatty liver (80%) and low high-density lipoproteins levels (84%). Family history of NAFLD (in any parent), higher alanine aminotransferase levels and higher total cholesterol levels in the child independently predicted possibility of NAFLD, but similar results could not be replicated for PNPLA3 gene polymorphism. Controlled attenuation parameter measurement (by transient elastography) had high sensitivity and specificity to diagnose steatosis. CONCLUSIONS There is high familial incidence of metabolic diseases in children with NAFLD. Controlled attenuation parameter can be useful as a non-invasive modality to screen fatty liver in children.
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Microbial Lipase Mediated by Health Beneficial Modification of Cholesterol and Flavors in Food Products: A Review.
Sharma, R, Sharma, N
Recent patents on biotechnology. 2018;(2):81-91
Abstract
BACKGROUND The tremendous need of lipase for varied applications in biotechnology increases its economical value in food and allied industries. Patents suggest that lipase has an impressive number of applications viz. enhancements of flavor in food products (Cheese, butter, alcoholic beverages, milk chocolate and diet control food stuffs), detergent industry in removing oil, grease stain, organic chemical processing, textile industry, oleochemical industry, cosmetic industry and also as therapeutic agents in pharmaceutical industries. OBJECTIVE This communication extends the frontier of lipase catalyzed benefits to human body by lowering serum cholesterol and enhancement of flavor in different food products. METHODS Among all, multiple innovations going on in the field of lipase applications are widening its scope in food industries consistently. Therefore, in the present work an effort has been made to explore the utilization of lipase in the field of food product enhancement. RESULTS Supplementation of food products with lipase results in modification of its physical, chemical and biochemical properties by enhancing its therapeutic activity. CONCLUSION Lipases are the most important enzymes used in food industries. They are utilized as industrial catalysts for lipid hydrolysis. Because of lipases hydrolysis nature it is widely exploited to catalyze lipids or fats in different food products and enhancement of food flavors.
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Optimization of lipase-catalyzed synthesis of β-sitostanol esters by response surface methodology.
Hakalin, NLS, Molina-Gutiérrez, M, Prieto, A, Martínez, MJ
Food chemistry. 2018;:139-148
Abstract
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.
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The PNPLA3 I148M variant is associated with transaminase elevations in type 2 diabetes patients treated with basal insulin peglispro.
Pillai, S, Duvvuru, S, Bhatnagar, P, Foster, W, Farmen, M, Shankar, S, Harris, C, Bastyr, E, Hoogwerf, B, Haupt, A
The pharmacogenomics journal. 2018;(3):487-493
Abstract
Basal insulin peglispro (BIL) is a novel insulin with hepato-preferential action. In phase 3 trials, BIL showed significantly improved glycemic control but higher levels of transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), triglycerides (TGs) and liver fat content (LFC) compared with insulin glargine (GL). As variants in PNPLA3 (I148M) and TM6SF2 (E167K) are associated with nonalcoholic fatty liver disease, we assessed these variants in type 2 diabetes (T2D) patients randomized to receive BIL (n=1822) or GL (n=1270) in three phase 3 trials. Magnetic resonance imaging assessments of LFC were conducted in a subset of patients (n=296). Analyses showed α-corrected significant increases in change from baseline in AST (P=0.0004) and nominal increases in ALT (P=0.019), and LFC (P=0.035) for PNPLA3 (148M/M) genotypes in the BIL arm at 26 weeks but no significant associations in GL. PNPLA3 (148M/M) was also associated with increases in total cholesterol (P=0.014) and low-density lipoprotein cholesterol (P=0.005) but not with hemoglobin A1c or TG. T2D patients with the PNPLA3 (148M/M) genotype treated with BIL may be more susceptible to increased liver fat deposition. The current data provide further insights into the biological role of PNPLA3 in lipid metabolism.
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10.
The triolein/aqueous interface and lipase activity studied by spectroscopic ellipsometry and coarse grained simulations.
Stamm, A, Svendsen, A, Skjold-Jørgensen, J, Vissing, T, Berts, I, Nylander, T
Chemistry and physics of lipids. 2018;:37-43
Abstract
In spite of the importance of the triglyceride aqueous interface for processes like emulsification, surfactant interactions and lipase activity, relatively little is known about this interface compared to that between alkanes and water. Here, the contact between triolein and water was investigated in terms of water inclusion in the oil phase and orientation of the molecules at the interface. Coarse grained models of triglycerides in contact with water were constructed and correlated with experimental results of the changes in thickness and refractive index, obtained using spectroscopic ellipsometry of spin-coated triolein films. The topography of the layer was revealed by atomic force microscopy. Dry triolein and a triolein sample after equilibration with water were also compared structurally using small-angle X-ray scattering. Additionally, the kinetics of adsorption/activity of three different variants of the Thermomyces lanuginosus lipase (TLL) were investigated. The results show that uptake of water in the triolein phase leads to increase in thickness of the layer. The observed increase of thickness was further enhanced by an active lipase but reduced when an inactive mutant of the enzyme was applied.