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Comparison of macauba and soybean oils as substrates for the enzymatic biodiesel production in ultrasound-assisted system.
Santin, CMT, Michelin, S, Scherer, RP, Valério, A, Luccio, MD, Oliveira, D, Oliveira, JV
Ultrasonics sonochemistry. 2017;(Pt A):525-528
Abstract
The objective of this study is to evaluate the batch enzymatic production of biodiesel in solvent-free system under ultrasound using as substrates ethanol, soybean oil and macauba fruit oil. For this purpose, a Plackett & Burman experimental design was carried out for soybean oil while a 24-1 design was conducted for macauba oil in order to maximize the biodiesel conversion for each system. Good conversions to fatty acid ethyl esters (FAEE), 88% for soybean oil and 75.2% for macauba oil, was obtained thus demonstrating the potential use of ultrasound for this reaction system.
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The PNPLA3 I148M variant modulates the fibrogenic phenotype of human hepatic stellate cells.
Bruschi, FV, Claudel, T, Tardelli, M, Caligiuri, A, Stulnig, TM, Marra, F, Trauner, M
Hepatology (Baltimore, Md.). 2017;(6):1875-1890
Abstract
UNLABELLED The genetic polymorphism I148M of patatin-like phospholipase domain-containing 3 (PNPLA3) is robustly associated with hepatic steatosis and its progression to steatohepatitis, fibrosis, and cancer. Hepatic stellate cells (HSCs) are key players in the development of liver fibrosis, but the role of PNPLA3 and its variant I148M in this process is poorly understood. Here we analyzed the expression of PNPLA3 during human HSC activation and thereby explored how a PNPLA3 variant impacts hepatic fibrogenesis. We show that expression of PNPLA3 gene and protein increases during the early phases of activation and remains elevated in fully activated HSCs (P < 0.01). Knockdown of PNPLA3 significantly decreases the profibrogenic protein alpha-smooth muscle actin (P < 0.05). Primary human I148M HSCs displayed significantly higher expression and release of proinflammatory cytokines, such as chemokine (C-C motif) ligand 5 (P < 0.01) and granulocyte-macrophage colony-stimulating factor (P < 0.001), thus contributing to migration of immune cells (P < 0.05). Primary I148M HSCs showed reduced retinol (P < 0.001) but higher lipid droplet content (P < 0.001). In line with this, LX-2 cells stably overexpressing I148M showed augmented proliferation and migration, lower retinol, and abolished retinoid X receptor/retinoid A receptor transcriptional activities but more lipid droplets. Knockdown of I148M PNPLA3 (P < 0.001) also reduces chemokine (C-C motif) ligand 5 and collagen1α1 expression (P < 0.05). Notably, I148M cells display reduced peroxisome proliferator-activated receptor gamma transcriptional activity, and this effect was attributed to increased c-Jun N-terminal kinase, thereby inhibiting peroxisome proliferator-activated receptor gamma through serine 84 phosphorylation and promoting activator protein 1 transcription. Conversely, the c-Jun N-terminal kinase inhibitor SP600125 and the peroxisome proliferator-activated receptor gamma agonist rosiglitazone decreased activator protein 1 promoter activity. CONCLUSIONS These data indicate that PNPLA3 is required for HSC activation and that its genetic variant I148M potentiates the profibrogenic features of HSCs, providing a molecular mechanism for the higher risk of progression and severity of liver diseases conferred to patients carrying the I148M variant. (Hepatology 2017;65:1875-1890).
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LEADER 3--lipase and amylase activity in subjects with type 2 diabetes: baseline data from over 9000 subjects in the LEADER Trial.
Steinberg, WM, Nauck, MA, Zinman, B, Daniels, GH, Bergenstal, RM, Mann, JF, Steen Ravn, L, Moses, AC, Stockner, M, Baeres, FM, et al
Pancreas. 2014;(8):1223-31
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Abstract
OBJECTIVES This report from the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial describes baseline lipase and amylase activity in type 2 diabetic subjects without acute pancreatitis symptoms before randomization to the glucagonlike peptide analog liraglutide or placebo. METHODS The LEADER is an international randomized placebo-controlled trial evaluating the cardiovascular safety of liraglutide in 9340 type 2 diabetic patients at high cardiovascular risk. Fasting lipase and amylase activity was assessed at baseline, before receiving liraglutide or placebo, using a commercial assay (Roche) with upper limit of normal values of 63 U/L for lipase and 100 U/L for amylase. RESULTS Either or both enzymes were above the upper limit of normal in 22.7% of subjects; 16.6% (n = 1540) had an elevated lipase level (including 1.2% >3-fold elevated), and 11.8% (n = 1094) had an elevated amylase level (including 0.2% >3-fold elevated). In multivariable regression models, severely reduced kidney function was associated with the largest effect on increasing activity of both. However, even among subjects with normal kidney function, 12.2% and 7.7% had elevated lipase and amylase levels. CONCLUSIONS In this large study of type 2 diabetic patients, nearly 25% had elevated lipase or amylase levels without symptoms of acute pancreatitis. The clinician must take these data into account when evaluating abdominal symptoms in type 2 diabetic patients.
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Long-term effects of lipase inhibition by orlistat on gastric emptying and orocecal transit time of a solid meal.
Kocełak, P, Zahorska-Markiewicz, B, Jonderko, K, Olszanecka-Glinianowicz, M, Zak-Gołab, A, Holecki, M, Kamińska, M, Szymszal, M
Journal of gastroenterology. 2008;(8):609-17
Abstract
BACKGROUND We assessed the impact of a prolonged lipase inhibition upon gastric emptying (GE) and orocecal transit time (OCTT) of a 355-kcal low-fat solid meal. METHODS In double-blind manner, 40 obese women BMI > 30 kg/m2, randomly allocated into two equal groups, took orally t.i.d. 120 mg orlistat or placebo during 8 weeks of a weight-reducing management. At randomization and after 2 months, GE was measured simultaneously with OCTT by means of a 13C-octanoic acid and a hydrogen breath test, respectively. Lipolytic activity was evaluated with a 13C-mixed triglyceride breath test (13C-MTGBT). RESULTS A profound lipase inhibition by orlistat was confirmed by a 79.5% +/- 16.9% reduction of the cumulative 6-h 13C recovery with 13CMTGBT. GE remained unchanged either in the orlistat (T1/2, 188 +/- 35 min start versus 198 +/- 36 min end) or the placebo (T1/2, 191 +/- 35 min start versus 180 +/- 39 min end) group. OCTT increased from 208 +/- 54 min to 271 +/- 64 min (P < 0.01) after orlistat treatment and did not change significantly (216 +/- 76 vs. 234 +/- 72 min) in the placebo group. CONCLUSIONS No adverse effect on the GE and a moderate prolongation of the OCTT of a low-fat solid meal is to be expected under a prolonged treatment with orlistat at a typical dosage regimen.
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Genetic variation in the hepatic lipase gene is associated with combined hyperlipidemia, plasma lipid concentrations, and lipid-lowering drug response.
Cenarro, A, Artieda, M, Gonzalvo, C, Meriño-Ibarra, E, Arístegui, R, Gañán, A, Díaz, C, Sol, JM, Pocoví, M, Civeira, F, et al
American heart journal. 2005;(6):1154-62
Abstract
BACKGROUND Combined hyperlipidemia (CHL) is a very frequent dyslipidemia, being lipid-lowering drugs often necessary in its management. Some genetic loci have been associated with CHL, and modulation of lipid-lowering treatment by genetic polymorphisms has been reported. We have investigated whether common polymorphisms in the hepatic lipase gene (LIPC) influence the baseline lipid concentration and the response to atorvastatin or bezafibrate in patients with CHL. METHODS Two genetic polymorphisms in LIPC (-514C-->T and +651A-->G) were determined by polymerase chain reaction and restriction analysis in 118 subjects of the ATOMIX (Atorvastatin in Mixed dyslipidemia) study who were randomized to treatment with either atorvastatin or bezafibrate and in 114 normolipidemic controls. RESULTS The -514T allele frequency was higher in the ATOMIX group (0.297) than in the control group (0.193) (P = .01). The -514T allele carriers in the control group showed higher high-density lipoprotein cholesterol (HDL-C) concentrations than the -514C homozygotes, 50.8 +/- 1.86 versus 45.9 +/- 1.40 mg/dL (P = .02). The +651G carriers in the ATOMIX group showed lower total cholesterol and low-density lipoprotein cholesterol than the +651A homozygotes, 274 +/- 3.72 and 181 +/- 3.50 mg/dL versus 289 +/- 4.0 and 194 +/- 3.76 mg/dL, respectively (P < .01). Homozygotes for the -514C allele on bezafibrate treatment had greater decrease in triglycerides and greater increase in HDL-C than -514T allele carriers after 12 months of bezafibrate treatment, -39.4% and +35.8% versus -25.5% and +20.4%, respectively (P = .080 and P = .007, respectively). CONCLUSIONS A higher frequency of the -514T allele of LIPC suggests a role of this locus in the pathogenesis of CHL. The -514T allele is associated with higher HDL-C concentration in normolipidemic population. The -514C-->T polymorphism modulates the lipid-lowering response to bezafibrate, with a better effect in homozygous CC subjects.
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Lipoprotein metabolism in subjects with hepatic lipase deficiency.
Tilly-Kiesi, M, Schaefer, EJ, Knudsen, P, Welty, FK, Dolnikowski, GG, Taskinen, MR, Lichtenstein, AH
Metabolism: clinical and experimental. 2004;(4):520-5
Abstract
A heritable deficiency of hepatic lipase (HL) provides insights into the physiologic function of HL in vivo. The metabolism of apolipoprotein B (apoB)-100 in very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) and of apoA-I and apoA-II in high-density lipoprotein (HDL) particles lipoprotein (Lp)(AI) and Lp(AI:AII) was assessed in 2 heterozygous males for compound mutations L334F/T383M or L334F/R186H, with 18% and 22% of HL activity, respectively, compared with 6 control males. Subjects were provided with a standard Western diet for a minimum of 3 weeks. At the end of the diet period, apo kinetics was assessed using a primed-constant infusion of [5,5,5-(2)H(3)] leucine. Mean plasma triglyceride (TG) and HDL cholesterol levels were 55% and 12% higher and LDL cholesterol levels 19% lower in the HL patients than control subjects. A higher proportion of apoB-100 was in the VLDL than IDL and LDL fractions of HL patients than control subjects due to a lower VLDL apoB-100 fractional catabolic rate (FCR) (4.63 v 9.38 pools/d, respectively) and higher hepatic production rate (PR) (33.24 v 10.87 mg/kg/d). Delayed FCR of IDL (2.78 and 6.31 pools/d) and LDL (0.128 and 0.205 pools/d) and lower PR of IDL (3.67 and 6.68 mg/kd/d) and LDL 4.57 and 13.07 mg/kg/d) was observed in HL patients relative to control subjects, respectively. ApoA-I FCR (0.09 and 0.13 pools/d) and PR (4.01 and 6.50 mg/kg/d) were slower in Lp(AI:AII) particles of HL patients relative to control subjects, respectively, accounting for the somewhat higher HDL cholesterol levels. HL deficiency may result in a lipoprotein pattern associated with low heart disease risk.
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Optimization of extracellular lipase production by Geotrichum sp. using factorial design.
Burkert, JF, Maugeri, F, Rodrigues, MI
Bioresource technology. 2004;(1):77-84
Abstract
Response surface methodology was employed to study the effects of carbon source (soy oil, olive oil and glucose) and nitrogen source concentrations (corn steep liquor and NH(4)NO(3)) on the lipase production by Geotrichum sp. The experiment included a 2(4) central composite rotatable design (CCRD) and four others 2(3) CCRD. According to the responses from the experimental designs, the effects of each variable were calculated and the interactions between them were determined. The response surface methodology was applied for the optimization of the nutrient concentrations in the culture medium for the enzyme production, at 30 degrees C. The optimum medium composition for lipase production by Geotrichum sp. was ammonium nitrate 2.1-2.5%, corn steep liquor 13-15% and soy oil 0.6% as carbon source, which lead to a lipase activity of about 20 U/ml. Using olive oil as carbon source, the optimum composition was ammonium nitrate 0.8-1%, corn steep liquor 13-15% and olive oil 0.6%, leading to an activity of 17 U/ml.
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XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients.
Torgerson, JS, Hauptman, J, Boldrin, MN, Sjöström, L
Diabetes care. 2004;(1):155-61
Abstract
OBJECTIVE It is well established that the risk of developing type 2 diabetes is closely linked to the presence and duration of overweight and obesity. A reduction in the incidence of type 2 diabetes with lifestyle changes has previously been demonstrated. We hypothesized that adding a weight-reducing agent to lifestyle changes may lead to an even greater decrease in body weight, and thus the incidence of type 2 diabetes, in obese patients. RESEARCH DESIGN AND METHODS In a 4-year, double-blind, prospective study, we randomized 3,305 patients to lifestyle changes plus either orlistat 120 mg or placebo, three times daily. Participants had a BMI ≥30 kg/m2 and normal (79%) or impaired (21%) glucose tolerance (IGT). Primary endpoints were time to onset of type 2 diabetes and change in body weight. Analyses were by intention to treat. RESULTS Of orlistat-treated patients, 52% completed treatment compared with 34% of placebo recipients (P < 0.0001). After 4 years' treatment, the cumulative incidence of diabetes was 9.0% with placebo and 6.2% with orlistat, corresponding to a risk reduction of 37.3% (P = 0.0032). Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT. Mean weight loss after 4 years was significantly greater with orlistat (5.8 vs. 3.0 kg with placebo; P < 0.001) and similar between orlistat recipients with impaired (5.7 kg) or normal glucose tolerance (NGT) (5.8 kg) at baseline. A second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group (3.6 vs. 1.4 kg; P < 0.001). CONCLUSIONS Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the IGT subgroup; weight loss was similar in subjects with IGT or NGT [correction].
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Comparison of the effect of orlistat vs orlistat plus metformin on weight loss and insulin resistance in obese women.
Sari, R, Balci, MK, Coban, E, Yazicioglu, G
International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity. 2004;(8):1059-63
Abstract
BACKGROUND AND AIM Orlistat and metformin are the currently used drugs for weight loss. We aimed to compare the effect of orlistat and orlistat plus metformin combination therapy on weight loss and insulin resistance in obese women. PATIENTS AND METHODS In all, 57 obese women (body mass index ≥30 kg/m(2) and normal glucose tolerance) were included. All subjects took the same content and caloric diet therapy during the study. After a month of diet period, each individual was randomly assigned to receive 360 mg orlistat per day (group 1; n=30) or 360 mg orlistat plus 1700 mg metformin per day (group 2; n=27) during the next 3 months. Body weight and insulin resistance by the homeostasis model assessment model (HOMA-IR) was measured at baseline, first month and fourth month. RESULTS The mean weight loss in groups 1 and 2 was 1.36+/-0.8 kg (1.4+/-0.7%) and 1.11+/-0.7 kg (1.1+/-0.7%) from baseline to first month; 4.8+/-2.9 kg (5.28+/-3.0%) and 5.77+/-2.5 kg (6.17+/-2.9%) from first month to fourth month. Body weight was decreased in groups 1 (P< 0.001) and 2 (P< 0.001), but there was no statistically significant difference between groups. Change of HOMA-IR in groups 1 and 2 was 0.41+/-0.4 (14.9+/-10.1%) and 0.23+/-0.7 (8.16+/-12.3%) from baseline to first month; 0.49+/-0.77 (22.0+/-26%) and 0.95+/-0.88 (34.8+/-29.1%) from first month to fourth month. HOMA-IR value was decreased in groups 1 (P< 0.001) and 2 (P< 0.001) but was not different between groups during the study period. CONCLUSIONS Combination of orlistat with metformin did not result in an additional effect on weight loss and insulin resistance when compared to orlistat alone in our study. However, new studies which have more sample sizes and the longer study period are necessary for this purpose.
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A novel streptomycete lipase: cloning, sequencing and high-level expression of the Streptomyces rimosus GDS(L)-lipase gene.
Vujaklija, D, Schröder, W, Abramić, M, Zou, P, Lescić, I, Franke, P, Pigac, J
Archives of microbiology. 2002;(2):124-30
Abstract
An extracellular lipase from Streptomyces rimosus R6-554W has been recently purified and biochemically characterized. In this report the cloning, sequencing, and high-level expression of its gene is described. The cloned DNA contained an ORF of 804 bp encoding a 268-amino-acid polypeptide with 34 amino acid residues at the amino terminus of the sequence that were not found in the mature protein. The theoretical molecular mass (24.172 kDa) deduced from the amino acid sequence of the mature enzyme was experimentally confirmed. This lipase showed no overall amino acid sequence similarity to other lipases in the databases. However, two hypothetical proteins, i. e. putative hydrolases, derived from the genome sequencing data of Streptomyces coelicolor A3(2), showed 66% and 33% identity. In addition, a significant similarity to esterases from Streptomyces diastatochromogenes and Aspergillus terreus was found. Sequence analysis revealed that our novel S. rimosus lipase containing a GDS(L)-like consensus motif belongs to family II of lipolytic enzymes, previously unrecognized in Streptomyces. When the lipase gene was expressed in a S. rimosus lipase-deficient strain harboring the lipase gene on a high-copy-number vector, lipase activity was 22-fold higher than in the original strain.