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1.
Arq. bras. med. vet. zootec. (Online) ; 73(4): 929-937, Jul.-Aug. 2021. tab, graf, ilus
Article in English | ID: biblio-1285261

ABSTRACT

The objective of the present study was to investigate the different plasma metabolites between anestrus and estrus postpartum dairy cows and to provide a theoretical basis for prevention of anestrus in dairy farm cows. In the experiment, one hundred and sixty-seven Holstein dairy cows were selected with similar age and parity. According to the concentration of ß-hydroxybutyric acid, non-esterified fatty acids and glucose in plasma during 14 to 21 days in milk, all dairy cows were determined as having a status of energy balance. According to the results of clinical symptom, rectal and B ultrasound examination at 60 to 90 days postpartum, these cows were divided into twenty estrus and twenty-four anestrus group, other dairy cows were removed. 1H nuclear magnetic resonance technology was utilized to detect the plasma metabolites changes and screen different plasma metabolites between anestrus and estrus cows. Ten different metabolites including alanine, glutamic acid, asparagine, creatine, choline, phosphocholine, glycerophosphocholine, low-density lipoprotein, and very-low-density lipoprotein were significantly decreased in anestrous cows compared with estrous cows. Metabolic pathway analyses indicated that differential metabolites were primarily involved in amino acid and glycerophospholipid metabolism. These metabolites and their enrichment pathways indicate that reduced steroid hormone synthesis precursors result in lower levels of estradiol and progesterone and cause anestrus in negative energy balance. These data provide a better understanding of the changes that may affect estrus of postpartum dairy cows at NEB status and lay the ground for further research.(AU)


O objetivo do presente estudo foi investigar os diferentes metabolitos do plasma entre o cio e o cio pós-parto de vacas leiteiras e fornecer uma base teórica para a prevenção do cio de vacas em fazendas de leite. No experimento, foram selecionadas 127 vacas leiteiras Holstein com idade e paridade similares. De acordo com a concentração de ß- ácido hidroxibutírico, ácidos graxos não esterificados e glicose no plasma entre 14 e 21 dias no leite, todas as vacas leiteiras foram determinadas em estado de equilíbrio energético. De acordo com os resultados dos sintomas clínicos, do exame de ultra-som retal e B aos 60 a 90 dias pós-parto, estas vacas foram divididas em vinte cios e vinte e quatro grupos de cio, outras vacas leiteiras foram removidas. A tecnologia de ressonância magnética nuclear 1H foi utilizada para detectar as alterações dos metabólitos plasmáticos e para triar diferentes metabólitos plasmáticos entre as vacas do cio e do cio. Dez diferentes metabólitos incluindo alanina, ácido glutâmico, asparagina, creatina, colina, fosfocholina, glicerofosfocolina, lipoproteína de baixa densidade e lipoproteína de muito baixa densidade foram significativamente diminuídos nas vacas antróficas em comparação com as vacas estro. As análises da via metabólica indicaram que os metabólitos diferenciais estavam principalmente envolvidos no metabolismo de aminoácidos e glicerofosfolipídios. Estes metabólitos e suas vias de enriquecimento indicam que a redução dos precursores da síntese de hormônios esteróides resulta em níveis mais baixos de estradiol e progesterona e causa anestros no balanço energético negativo. Estes dados fornecem uma melhor compreensão das mudanças que podem afetar o cio das vacas leiteiras pós-parto no estado de NEB e preparam o terreno para mais pesquisas.(AU)


Subject(s)
Animals , Female , Cattle , Progesterone/analysis , Anestrus/blood , Estrus/blood , Postpartum Period/blood , Estradiol/analysis , Glycerophospholipids , Fatty Acids, Nonesterified , Amino Acids , Glucose , Hematologic Tests/veterinary
2.
Arq. bras. med. vet. zootec. (Online) ; 72(4): 1545-1554, July-Aug. 2020. tab
Article in English | ID: biblio-1131469

ABSTRACT

This study aimed to evaluate the effects of different nutritional plans on the productive, physiological and metabolic parameters of F1 ½ Holstein x ½ Zebu cows in different stages of lactation. Sixty lactating cows were allotted to a completely randomized 5 x 3 factorial design with five feed allowances and three lactation periods. The dry matter intake, milk yield and heart rate were reduced by 5.69kg, 2.41kg and 10.36 beats/min (morning) and 10.25 beats/min (afternoon) for each 1% feed restriction, respectively. There was no difference in the concentration of glucose, total protein, albumin, cholesterol and non-esterified fatty acids for cows subjected to different feed allowances, with means of 95.25, 7.98, 2.95, 121.68 and 0.45mg/dL, respectively. Feed restriction of up to 2.50% BW is a cost reduction strategy that does not alter milk yield, regardless of the stage of lactation.(AU)


Objetivou-se avaliar os efeitos de diferentes planos nutricionais sobre as características produtivas, fisiológicas e metabólicas de vacas F1 ½ Holandês x ½ Zebu. Foram utilizadas 60 vacas em lactação, seguindo-se o delineamento inteiramente ao acaso, em esquema fatorial 5 x 3, com cinco níveis de oferta de dieta e três períodos de lactação. À medida que se aumentou 1% na restrição da oferta da dieta, houve redução linear de 5,69kg no consumo de matéria seca pelos animais, 2,41kg na produção de leite, bem como de 10,36bat/min (manhã) e 10,25 bat/min (tarde) na frequência cardíaca dos animais. Não houve diferença para a concentração de glicose, proteínas totais, albumina, colesterol e NEFA com a restrição na oferta da dieta dos animais, sendo a média de 95,25, 7,98, 2,95, 121,68 e 0,45mg/dL, respectivamente. Recomenda-se a restrição de até 2,50% de peso corporal como estratégia de redução dos custos em todos os estágios em lactação, visando não alterar, economicamente, a produção de leite.(AU)


Subject(s)
Animals , Female , Cattle , Lactation , Cholesterol/analysis , Diet Therapy/veterinary , Glucose/analysis , Fatty Acids, Nonesterified , Respiratory Rate
3.
Arq. bras. med. vet. zootec. (Online) ; 72(2): 371-378, Mar./Apr. 2020. tab, graf
Article in English | ID: biblio-1128217

ABSTRACT

The aim of this study was to evaluate the metabolic, inflammatory, and hepatic aspects, as well as the milk yield in heifers submitted to protocol for induction of lactation compared to primiparous cows. Sixty Holstein heifers were selected and enrolled into two groups: Control (n= 30), pregnant heifers and Induction heifers (n= 30), non-pregnant femeales, submitted to a lactation induction protocol. Blood samples were collected at: pre-lactation period (weeks -3, -2 and -1) and post-lactation period (weeks 1, 2 and 3), aiming to evaluate glucose, non-esterified fatty acids, paraoxonase-1, albumin, ALT, GGT and cortisol. The protocol efficiently induced lactation in all the heifers, which produced 74.54% of the total production of milk from primiparous cows. In the pre-lactation period, induced animals presented higher concentrations of non-esterified fatty acids than the Control heifers, and the opposite was observed in the post lactation period. In both moments albumin and ALT were lower in the Induction group, and paraoxonase-1 activity and GGT concentrations were higher, compared to the Control. Thus, lactation induction protocol is efficient to initiate milk production in dairy heifers with no considerable changes in energetic, metabolic and hepatic profile when compared to heifers in physiological lactation.(AU)


O objetivo deste estudo foi avaliar os perfis metabólico, inflamatório, hepático e a produção de leite de novilhas induzidas à lactação comparadas a primíparas. Sessenta novilhas da raça Holandês foram selecionadas e alocadas em grupos: controle (n=30), novilhas prenhas, e indução (n=30), novilhas vazias submetidas a um protocolo de indução de lactação. As amostras de sangue foram coletadas nas semanas -3, -2 e -1 (pré-lactação) e nas semanas 1, 2 e 3 (pós-início de lactação) para avaliação de glicose, ácidos graxos não esterificados, paraoxonase-1, albumina, ALT, GGT e cortisol. O protocolo induziu eficientemente a lactação em todas as novilhas, que produziram 74,54% da produção total de leite do controle. No período pré-lactação, o grupo indução apresentou maiores concentrações de ácidos graxos não esterificados que o controle, e o oposto foi observado pós-lactação. Em ambos os momentos, albumina e ALT foram menores no grupo indução, e a atividade da paraoxonase-1 e as concentrações de GGT foram maiores, em comparação ao controle. Assim, o protocolo de indução de lactação foi eficiente para iniciar a produção de leite em novilhas induzidas, além de terem sido observadas alterações nos perfis energético, metabólico e hepático em comparação a novilhas em lactação fisiológica.(AU)


Subject(s)
Animals , Female , Cattle , Lactation/physiology , Hydrocortisone/analysis , Alanine Transaminase/analysis , Albumins/analysis , Fatty Acids, Nonesterified/analysis , gamma-Glutamyltransferase/analysis , Milk
4.
Arq. bras. med. vet. zootec. (Online) ; 72(2): 553-559, Mar./Apr. 2020. tab
Article in Portuguese | ID: biblio-1128404

ABSTRACT

Durante o periparto, as vacas leiteiras são submetidas a uma grande demanda de energia, ao mesmo tempo em que reduzem sua ingestão de matéria seca. O balanço energético negativo, resultante dessa equação, acarreta severos transtornos metabólicos, à produção e, principalmente, à reprodução. O objetivo do presente estudo foi avaliar o efeito da colina protegida sobre os parâmetros metabólicos, o intervalo entre parto e concepção e a produção de leite em vacas no período de transição. Cinquenta e quatro vacas leiteiras foram divididas em três grupos: controle, suplementação com colina por 10 dias pré-parto (T10) e suplementação com colina por 20 dias pré-parto (T20). Após o parto, foram mensurados os teores de frutosamina, colesterol, ácidos graxos não esterificados (AGNE), beta-hidroxibutirato (BHB), aspartato aminotransferase (AST), gamaglutamiltransferase (GGT) e total de oxidantes (TOS), nos dias 10, 20 e 30. Ainda foram avaliadas produção de leite e intervalo entre parto e concepção. Não houve efeito da suplementação com colina sobre os parâmetros sanguíneos e a produção. O intervalo entre parto e concepção foi menor no grupo T20. A colina suplementada por 20 dias durante o pré-parto melhorou a performance reprodutiva de vacas leiteiras(AU)


During the periparturient dairy cows undergo a large energy demand, at the same time reducing their intake of dry matter. The negative energy balance resulting from this equation leads to severe metabolic disorders in production, and mainly in reproduction. The aim of this study was to evaluate the effect of protected choline on metabolic parameters, reproductive performance, and milk production in cows during the transition period. Fifty-four dairy cows were divided into three groups: control, supplementation with choline for 10 days prepartum (T10) and supplementation with choline for 20 days prepartum (T20). After delivery we measured fructosamine levels, cholesterol, non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT), and total oxidant (TOS) on days 10, 20 and 30. We also evaluated milk production and interval between calving and conception. There was no effect of supplementation with choline on blood and production parameters. The interval between calving and conception was lower in the T20 group. Choline supplemented by 20 during the antepartum improved reproductive performance of dairy cows, although it did not change the metabolic profile.(AU)


Subject(s)
Animals , Female , Pregnancy , Cattle , Sexual Behavior, Animal , Choline/administration & dosage , Peripartum Period/physiology , Metabolism , Aspartate Aminotransferases , Cholesterol , 3-Hydroxybutyric Acid , Fatty Acids, Nonesterified , gamma-Glutamyltransferase
5.
Article in English | WPRIM | ID: wpr-787142

ABSTRACT

Medium- and long-chain triglyceride (MCT/LCT) propofol is widely used as an intravenous anesthetic, especially in the intensive care unit. The present study aimed to assess whether MCT/LCT propofol is safe in the hyperlipidemic population for long-term use. Free fatty acids (FFAs) were used to establish high-fat stimulation of HepG2 and Huh7 cells. Subsequently, these cells were treated with propofol at the concentration of 0, 4, or 8 µg/ml for 24 and 48 h. The results indicated that the cell viability was notably decreased when the cells were stimulated with 2 mmol/L FFAs and treated with 12 µg/ml MCT/LCT propofol. Accordingly, we chose 2 mmol/L FFAs along with 4 and 8 µg/ml MCT/LCT propofol for the subsequent experiments. Four and 8 µg/ml MCT/LCT propofol inhibited FFA-induced lipid accumulation in the cells and significantly reversed acetyl coenzyme A carboxylase (ACC) activity. In addition, MCT/LCT propofol not only significantly promoted the phosphorylation of AMPK and ACC, but also reversed the FFA-induced decreased phosphorylation of AMPK and ACC. In conclusion, MCT/LCT propofol reverses the negative effects caused by FFAs in HepG2 and Huh7 cells, indicating that MCT/LCT propofol might positively regulate lipid metabolism.


Subject(s)
Acetyl-CoA Carboxylase , AMP-Activated Protein Kinases , Cell Survival , Fatty Acids, Nonesterified , Hepatocytes , Intensive Care Units , Lipid Metabolism , Liver , Metabolism , Phosphorylation , Propofol , Triglycerides
6.
Article in English | WPRIM | ID: wpr-786082

ABSTRACT

Ceramides are minor components of the hepatic lipidome that have major effects on liver function. These products of lipid and protein metabolism accumulate when the energy needs of the hepatocyte have been met and its storage capacity is full, such that free fatty acids start to couple to the sphingoid backbone rather than the glycerol moiety that is the scaffold for glycerolipids (e.g., triglycerides) or the carnitine moiety that shunts them into mitochondria. As ceramides accrue, they initiate actions that protect cells from acute increases in detergent-like fatty acids; for example, they alter cellular substrate preference from glucose to lipids and they enhance triglyceride storage. When prolonged, these ceramide actions cause insulin resistance and hepatic steatosis, 2 of the underlying drivers of cardiometabolic diseases. Herein the author discusses the mechanisms linking ceramides to the development of insulin resistance, hepatosteatosis and resultant cardiometabolic disorders.


Subject(s)
Carnitine , Ceramides , Fatty Acids , Fatty Acids, Nonesterified , Fatty Liver , Glucose , Glycerol , Hepatocytes , Insulin Resistance , Liver , Metabolism , Mitochondria , Non-alcoholic Fatty Liver Disease , Triglycerides
7.
Article in English | WPRIM | ID: wpr-786078

ABSTRACT

Like other bodily materials, lipids such as plasma triacylglycerol, cholesterols, and free fatty acids are in a dynamic state of constant turnover (i.e., synthesis, breakdown, oxidation, and/or conversion to other compounds) as essential processes for achieving dynamic homeostasis in the body. However, dysregulation of lipid turnover can lead to clinical conditions such as obesity, fatty liver disease, and dyslipidemia. Assessment of “snap-shot” information on lipid metabolism (e.g., tissue contents of lipids, abundance of mRNA and protein and/or signaling molecules) are often used in clinical and research settings, and can help to understand one's health and disease status. However, such “snapshots” do not provide critical information on dynamic nature of lipid metabolism, and therefore may miss “true” origin of the dysregulation implicated in related diseases. In this regard, stable isotope tracer methodology can provide the in vivo kinetic information of lipid metabolism. Combining with “static” information, knowledge of lipid kinetics can enable the acquisition of in depth understanding of lipid metabolism in relation to various health and disease status. This in turn facilitates the development of effective therapeutic approaches (e.g., exercise, nutrition, and/or drugs). In this review we will discuss 1) the importance of obtaining kinetic information for a better understanding of lipid metabolism, 2) basic principles of stable isotope tracer methodologies that enable exploration of “lipid kinetics” in vivo, and 3) quantification of some aspects of lipid kinetics in vivo with numerical examples.


Subject(s)
Cholesterol , Dyslipidemias , Fatty Acids, Nonesterified , Fatty Liver , Homeostasis , Kinetics , Lipid Metabolism , Mass Spectrometry , Obesity , Plasma , RNA, Messenger , Triglycerides
8.
Article in English | WPRIM | ID: wpr-760344

ABSTRACT

We aimed to identify predictive markers of peri- and postpartum disorders in dairy cows. Data regarding peri- and postpartum disorders, serum metabolites, body condition score (BCS), and rectal temperature, were collected from 227 dairy cows, which were allocated to healthy (n = 57) and diseased (n = 170) groups. Serum non-esterified fatty acid (NEFA) concentration was higher in diseased than healthy cows 4 weeks before (p < 0.01) and immediately after (p = 0.05) calving. Serum alanine aminotransferase (AST) activity was higher (p < 0.05) in diseased than healthy cows 1 and 2 weeks after calving, whereas total cholesterol (TCH) concentration was lower (p < 0.05–0.0001) in diseased cows 4 weeks before, and after calving. BCS was higher (p < 0.05) in diseased than healthy cows 4 weeks before calving, but lower (p < 0.01) in diseased cows 8 weeks after calving. Rectal temperature was higher (p < 0.05–0.01) in diseased than healthy cows between 2 and 14 days postpartum. In conclusion, high serum NEFA and AST concentrations and lower TCH concentration during the peripartum period, and high prepartum BCS and postpartum rectal temperature, could be used as biomarkers to predict the subsequent development of peri- and postpartum disorders.


Subject(s)
Alanine Transaminase , Biomarkers , Cholesterol , Fatty Acids, Nonesterified , Peripartum Period , Postpartum Period
9.
Article in English | WPRIM | ID: wpr-763687

ABSTRACT

BACKGROUND: The apolipoprotein B/A1 (apoB/A1) ratio is a stronger predictor of future cardiovascular disease than is the level of conventional lipids. Statin and ezetimibe combination therapy have shown additional cardioprotective effects over statin monotherapy. METHODS: This was a single-center, randomized, open-label, active-controlled study in Korea. A total of 36 patients with type 2 diabetes mellitus were randomized to either rosuvastatin monotherapy (20 mg/day, n=20) or rosuvastatin/ezetimibe (5 mg/10 mg/day, n=16) combination therapy for 6 weeks. RESULTS: After the 6-week treatment, low density lipoprotein cholesterol (LDL-C) and apoB reduction were comparable between the two groups (−94.3±15.4 and −62.0±20.9 mg/dL in the rosuvastatin group, −89.9±22.7 and −66.8±21.6 mg/dL in the rosuvastatin/ezetimibe group, P=0.54 and P=0.86, respectively). In addition, change in apoB/A1 ratio (−0.44±0.16 in the rosuvastatin group and −0.47±0.25 in the rosuvastatin/ezetimibe group, P=0.58) did not differ between the two groups. On the other hand, triglyceride and free fatty acid (FFA) reductions were greater in the rosuvastatin/ezetimibe group than in the rosuvastatin group (−10.5 mg/dL [interquartile range (IQR), −37.5 to 29.5] and 0.0 µEq/L [IQR, −136.8 to 146.0] in the rosuvastatin group, −49.5 mg/dL [IQR, −108.5 to −27.5] and −170.5 µEq/L [IQR, −353.0 to 0.8] in the rosuvastatin/ezetimibe group, P=0.010 and P=0.049, respectively). Both treatments were generally well tolerated, and there were no differences in muscle or liver enzyme elevation. CONCLUSION: A 6-week combination therapy of low-dose rosuvastatin and ezetimibe showed LDL-C, apoB, and apoB/A1 ratio reduction comparable to that of high-dose rosuvastatin monotherapy in patients with type 2 diabetes mellitus. Triglyceride and FFA reductions were greater with the combination therapy than with rosuvastatin monotherapy.


Subject(s)
Apolipoprotein A-I , Apolipoproteins , Apolipoproteins B , Cardiovascular Diseases , Cholesterol, LDL , Diabetes Mellitus, Type 2 , Ezetimibe , Fatty Acids, Nonesterified , Hand , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Korea , Liver , Rosuvastatin Calcium , Triglycerides
10.
Article in English | WPRIM | ID: wpr-763036

ABSTRACT

Patients with diabetes mellitus (DM) often suffer from diverse skin disorders, which might be attributable to skin barrier dysfunction. To explore the role of lipid alterations in the epidermis in DM skin disorders, we quantitated 49 lipids (34 ceramides, 14 free fatty acids (FFAs), and cholesterol) in the skin epidermis, liver, and kidneys of db/db mice, a Type 2 DM model, using UPLC-MS/MS. The expression of genes involved in lipid synthesis was also evaluated. With the full establishment of hyperglycemia at the age of 20 weeks, remarkable lipid enrichment was noted in the skin of the db/db mice, especially at the epidermis and subcutaneous fat bed. Prominent increases in the ceramides and FFAs (>3 fold) with short or medium chains (

Subject(s)
Animals , Ceramides , Diabetes Mellitus , Diabetes Mellitus, Type 2 , Epidermis , Fatty Acids, Nonesterified , Humans , Hyperglycemia , Kidney , Liver , Mice , Receptors, Cytoplasmic and Nuclear , Skin , Stearoyl-CoA Desaturase , Subcutaneous Fat
11.
Article in Korean | WPRIM | ID: wpr-740565

ABSTRACT

PURPOSE: The skin pH is maintained by epidermal lactate, free fatty acids (FFAs), and free amino acids (FAAs). As a significant determinant of skin health, the skin pH is increased (less acidic) under abnormal and aged skin conditions. In a search for dietary alternatives that would promote an acidic skin pH, this study investigated the dietary effects of Lactobacillus plantarum CJLP55 isolated from Korean kimchi on the skin pH, and epidermal levels of lactate, FFAs, and FAAs in adult subjects. METHODS: Seventy eight subjects (mean age 24.9 ± 0.5 years, range 19 ~ 37 years) were assigned randomly to ingest CJLP55, Lactobacillus strain from kimchi, (n = 39, CJLP group) or placebo supplements (n = 39, placebo group) for 12 weeks in a double-blind, placebo-controlled trial. Skin pH and epidermal levels of lactate, FFAs and FFAs were assessed at 0, 6 and 12 weeks. RESULTS: Although significant decreases in skin pH were observed in both the CJLP and placebo groups at 6 weeks, the skin pH was decreased significantly only in the CJLP group at 12 weeks. In parallel, the epidermal level of lactate in the CJLP group was also increased by 25.6% at 12 weeks. On the other hand, the epidermal level of FAAs were not altered in the CJLP and placebo groups, but the epidermal level of total FFAs, including palmitic acid and stearic acid, was lower in the CJLP group than in the placebo group over 12 weeks. The changes in the other FFAs, such as palmitoleic acid and oleic acid, were similar in the CJLP and placebo groups over 12 weeks. CONCLUSION: Overall, a dietary supplement of CJLP55 promotes acidic skin pH with a selective increase in epidermal lactate in adult subjects.


Subject(s)
Adult , Amino Acids , Dietary Supplements , Fatty Acids, Nonesterified , Hand , Humans , Hydrogen-Ion Concentration , Lactic Acid , Lactobacillus plantarum , Lactobacillus , Oleic Acid , Palmitic Acid , Skin
12.
Article in English | WPRIM | ID: wpr-785705

ABSTRACT

BACKGROUND: Chronic exposure to elevated levels of free fatty acids contributes to pancreatic β-cell dysfunction. Although it is well known that metformin induces cellular energy depletion and a concomitant activation of AMP-activated protein kinase (AMPK) through inhibition of the respiratory chain, previous studies have shown inconsistent results with regard to the action of metformin on pancreatic β-cells. We therefore examined the effects of metformin on pancreatic β-cells under lipotoxic stress.METHODS: NIT-1 cells and mouse islets were exposed to palmitate and treated with 0.05 and 0.5 mM metformin. Cell viability, glucose-stimulated insulin secretion, cellular adenosine triphosphate, reactive oxygen species (ROS) levels and Rho kinase (ROCK) activities were measured. The phosphorylation of AMPK was evaluated by Western blot analysis and mRNA levels of endoplasmic reticulum (ER) stress markers and NADPH oxidase (NOX) were measured by real-time quantitative polymerase chain reaction analysis.RESULTS: We found that metformin has protective effects on palmitate-induced β-cell dysfunction. Metformin at a concentration of 0.05 mM inhibits NOX and suppresses the palmitate-induced elevation of ER stress markers and ROS levels in a AMPK-independent manner, whereas 0.5 mM metformin inhibits ROCK activity and activates AMPK.CONCLUSION: This study suggests that the action of metformin on β-cell lipotoxicity was implemented by different molecular pathways depending on its concentration. Metformin at a usual therapeutic dose is supposed to alleviate lipotoxic β-cell dysfunction through inhibition of oxidative stress and ER stress.


Subject(s)
Adenosine Triphosphate , AMP-Activated Protein Kinases , Animals , Blotting, Western , Cell Survival , Electron Transport , Endoplasmic Reticulum , Endoplasmic Reticulum Stress , Fatty Acids, Nonesterified , Insulin , Insulin-Secreting Cells , Metformin , Mice , NADPH Oxidases , Oxidative Stress , Phosphorylation , Polymerase Chain Reaction , Reactive Oxygen Species , rho-Associated Kinases , RNA, Messenger
13.
Braz. j. microbiol ; 49(4): 856-864, Oct.-Dec. 2018. graf
Article in English | LILACS | ID: biblio-974294

ABSTRACT

ABSTRACT The growth of yeasts in culture media can be affected by many factors. For example, methanol can be metabolized by other pathways to produce ethanol, which acts as an inhibitor of the heterologous protein production pathway; oxygen concentration can generate aerobic or anaerobic environments and affects the fermentation rate; and temperature affects the central carbon metabolism and stress response protein folding. The main goal of this study was determine the implication of free fatty acids on the production of heterologous proteins in different culture conditions in cultures of Pichia pastoris. We evaluated cell viability using propidium iodide by flow cytometry and thiobarbituric acid reactive substances to measure cell membrane damage. The results indicate that the use of low temperatures and low methanol concentrations favors the decrease in lipid peroxidation in the transition phase from glycerol to methanol. In addition, a temperature of 14 ºC + 1%M provided the most stable viability. By contrast, the temperature of 18 ºC + 1.5%M favored the production of a higher antibody fragment concentration. In summary, these results demonstrate that the decrease in lipid peroxidation is related to an increased production of free fatty acids.


Subject(s)
Pichia/metabolism , Fatty Acids, Nonesterified/metabolism , Pichia/growth & development , Pichia/genetics , Temperature , Recombinant Proteins/genetics , Culture Media/metabolism , Culture Media/chemistry , Methanol/metabolism , Fermentation , Glycerol/metabolism
14.
Arq. bras. cardiol ; 110(4): 339-347, Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-888048

ABSTRACT

Abstract Background: Lipid accumulation product (LAP), a simple and low-cost tool, is a novel biomarker of central lipid accumulation and represents a potential surrogate marker for atherogenic lipoprotein profile. However, its association with lipoprotein subfractions has not been described in the literature. Objective: To determine whether LAP index could be used as a marker of low- and high-density lipoprotein (LDL and HDL) size in Brazilian individuals. Methods: This cross-sectional study included patients (n = 351) of both sexes and age between 30-74 years. Clinical and sociodemographic data and family history of diseases were evaluated. Lipoprotein size, and levels of total cholesterol (TC), lipoproteins, apolipoprotein AI and B (APO AI/APO B), glucose, insulin, insulin resistance index (HOMA-IR) and non-esterified fatty acids (NEFA) were assessed in blood samples. LAP was calculated by the formulas [(waist circumference[cm]-58) × (triglycerides[mmol/L]) for women and (waist circumference [cm]-65) × (triglycerides [mmol/L]) for men]. The association between LAP and metabolic parameters were tested by linear trend (general linear model, GLM test) before and after multiple adjustments for potential confounders (sex, age, smoking, statin, fibrate, and hypoglycemic drugs) at significant level p < 0.05. Results: LAP was positively associated with TC, APO B, NEFA, glucose, insulin and HOMA-IR values, and negatively associated with HDL-C. Higher central lipid accumulation was corelated with higher percentage of intermediate HDL and of small LDL and HDL and less amount of large HDL. LDL size was also reduced in greater LAP index values. The negative impact of LAP was maintained after adjustment for multiple variables. Conclusion: LAP was robustly associated with atherogenic profile of lipoprotein subfractions, independently of multiple confounders.


Resumo Fundamento: O produto de acumulação lipídica (LAP), um instrumento simples e de baixo custo, é um novo biomarcador de acúmulo de gordura central e representa um marcador substituto potencial para o perfil aterogênico de lipoproteínas. No entanto, sua associação com subfrações de lipoproteínas ainda não foi descrita na literatura. Objetivo: Determinar se o LAP pode ser usado como um marcador de tamanho da lipoproteína de baixa densidade (LDL) e de alta densidade (HDL) em indivíduos brasileiros. Métodos: Este estudo transversal incluiu 351 pacientes de ambos os sexos e idade entre 30 e 74 anos. Dados clínicos e sociodemográficos e história familiar de doenças foram avaliados. O tamanho das lipoproteínas, e níveis de colesterol total (CT), lipoproteínas, apolipoproteína AI e B (APO AI/APO B), glicose, ácidos graxos não esterificados (AGNEs) e insulina, e índice de resistência insulínica (HOMA-IR) foram avaliados em amostras de sangue. O LAP foi calculado utilizando-se as fórmulas (circunferência da cintura (cm]-58) × (triglicerídeos[mmol/L]) para mulheres e (circunferência da cintura[cm]-65) × (triglicerídeos [mmol/L]) para homens. Associações entre LAP e parâmetros metabólicos foram testadas por tendência linear (modelo linear generalizado, GLM) antes e após ajustes por fatores de confusão (sexo, idade, tabagismo, uso de estatinas, fibratos e hipoglicemiantes) ao nível de significância de p < 0,05). Resultados: LAP apresentou uma associação positiva com CT, APO B, AGNEs, glicose, insulina, HOMA-IR, e uma associação negativa com HDL-C. Maior acúmulo de gordura central correlacionou-se com maior porcentagem de HDL intermediária e de partículas pequenas de LDL e HDL, e menor porcentagem de HDL grande. O tamanho da LDL também era reduzido em valores de LAP mais elevados. O impacto negativo do LAP foi mantido após ajuste para múltiplas variáveis. Conclusão: o LAP esteve fortemente associado com o perfil aterogênico de subfrações de lipoproteínas, independetemente dos fatores de confusão.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Risk Assessment/methods , Atherosclerosis/blood , Lipid Accumulation Product/physiology , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Apolipoproteins B/blood , Reference Values , Blood Glucose/analysis , Brazil , Insulin Resistance , Biomarkers/blood , Cardiovascular Diseases/etiology , Cardiovascular Diseases/blood , Sex Factors , Anthropometry , Epidemiologic Methods , Apolipoprotein A-I/blood , Atherosclerosis/ethnology , Fatty Acids, Nonesterified/blood , Lipid Accumulation Product/ethnology , Insulin/blood
15.
Article in Chinese | WPRIM | ID: wpr-771480

ABSTRACT

OBJECTIVE@#To investigate the effects of sera from rats fed with tablets (HGT) on endoplasmic reticulum (ER) stress in a steatotic hepatocyte model of free fatty acids (FFAs)-induced nonalcoholic fatty liver disease (NAFLD) and explore the possible mechanism.@*METHODS@#FFAs prepared by mixing oleic acid and palmitic acid at the ratio of 2:1. HepG2 cells were treated with the sera from rats fed with low-, moderate-or high-dose HGT (HGT sera) or sera of rats fed with fenofibrate (fenofibrate sera), followed by treatment with 1 mmol/L FFAs for 24 h to induce hepatic steatosis. Oil red O staining was used to observe the distribution of lipid droplets in the cells. The biochemical parameters including triglyceride (TG), lactated hydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured using a commercial kit. The morphological changes of the ER in the cells were observed using transmission electron microscopy. The protein/mRNA expressions of ER stress-related signal molecules including GRP78, PERK, p-PERK, ATF6, ATF4, CASPASE-12, CHOP, XBP-1, PKC, and p-PKC-δ were detected using Western blotting and/or quantitative real-time PCR (qRT-PCR). The changes in the protein expressions of GRP78, p-PERK, CASPASE-12 and CHOP were also detected in cells with transient transfection of PKC-δ siRNA for PKC-δ knockdown.@*RESULTS@#Compared with the control cells, the cells treated with FFAs showed significantly increased levels of TG, AST, and ALT ( < 0.05). Compared with FFAs-treated cells, the cells pretreated with HGT sera or fenofibrate sera all showed significantly decreased TG, AST and ALT levels ( < 0.05), reduced accumulation of the lipid droplets ( < 0.05), and lowered protein or mRNA expression levels of GRP78, p-PERK, ATF6, ATF4, CHOP, CASPASE-12, XBP-1 and p-PKC-δ ( < 0.05). PKC-δ knockdown caused significantly reduced protein expressions of GRP78, p-PERK, CASPASE-12 and CHOP in the cells with FFA-induced hepatic steatosis ( < 0.001); treatment with high-dose HGT serum more significantly reduced the expressions of GRP78 ( < 0.001) and P-PERK ( < 0.01) in FFAs-induced cells with PKC-δ knockdown.@*CONCLUSIONS@#HGT serum can effectively prevent FFAs-induced steatosis in HepG2 cells by alleviating ER stress, in which PKC-δ may act as an important target.


Subject(s)
Alanine Transaminase , Blood , Animals , Aspartate Aminotransferases , Blood , Disease Models, Animal , Drugs, Chinese Herbal , Endoplasmic Reticulum , Endoplasmic Reticulum Stress , Fatty Acids, Nonesterified , Fenofibrate , Hep G2 Cells , Humans , Hypolipidemic Agents , Microscopy, Electron, Transmission , Non-alcoholic Fatty Liver Disease , Blood , RNA, Messenger , Blood , Rats , Serum , Tablets , Triglycerides , Blood
16.
Article in English | WPRIM | ID: wpr-787110

ABSTRACT

BACKGROUND: Body fats, especially both of abdominal fat pad mass and skeletal muscle fat content, are inversely related to insulin action. Therefore, methods for decreasing visceral fat mass and muscle triglyceride content may be helpful for the prevention of insulin resistance.METHODS: Thalidomide, used for its anti-angiogenic and anti-inflammatory properties, was administered to rats for 4 weeks. A 10% solution of thalidomide in dimethyl sulfoxide was injected daily into the peritoneal cavity as much as 100 mg/kg of body weight.RESULTS: The total visceral fat pad mass in the thalidomide-treated group was 11% lower than in the control group. The size of adipocytes of the epididymal fat pad mass in the thalidomide-treated group was smaller than in the control group. The intraperitoneal thalidomide treatment increased triglyceride concentrations by 16% in the red muscle, but not in the white muscle.CONCLUSION: The results suggested that intraperitoneal thalidomide treatment inhibited abdominal fat accumulation, and that the free fatty acids in the blood were preferentially accumulated in the red muscle rather than in the white muscle.


Subject(s)
Abdominal Fat , Adipocytes , Adipose Tissue , Animals , Body Weight , Dimethyl Sulfoxide , Fatty Acids, Nonesterified , Insulin , Insulin Resistance , Intra-Abdominal Fat , Muscle, Skeletal , Peritoneal Cavity , Rats , Thalidomide , Triglycerides
17.
Article in English | WPRIM | ID: wpr-713309

ABSTRACT

BACKGROUND/AIMS: Hepatic steatosis is caused by an imbalance between free fatty acids (FFAs) uptake, utilization, storage, and disposal. Understanding the molecular mechanisms involved in FFAs accumulation and its modulation could drive the development of potential therapies for Nonalcoholic fatty liver disease. The aim of the current study was to explore the effects of picroside II, a phytoactive found in Picrorhiza kurroa, on fatty acid accumulation vis-à-vis silibinin, a known hepatoprotective phytoactive from Silybum marianum. METHODS: HepG2 cells were loaded with FFAs (oleic acid:palmitic acid/2:1) for 20 hours to mimic hepatic steatosis. The FFAs concentration achieving maximum fat accumulation and minimal cytotoxicity (500 μM) was standardized. HepG2 cells were exposed to the standardized FFAs concentration with and without picroside II pretreatment. RESULTS: Picroside II pretreatment inhibited FFAs-induced lipid accumulation by attenuating the expression of fatty acid transport protein 5, sterol regulatory element binding protein 1 and stearoyl CoA desaturase. Preatreatment with picroside II was also found to decrease the expression of forkhead box protein O1 and phosphoenolpyruvate carboxykinase. CONCLUSIONS: These findings suggest that picroside II effectively attenuated fatty acid accumulation by decreasing FFAs uptake and lipogenesis. Picroside II also decreased the expression of gluconeogenic genes.


Subject(s)
Fatty Acid Transport Proteins , Fatty Acids, Nonesterified , Hep G2 Cells , Lipogenesis , Milk Thistle , Non-alcoholic Fatty Liver Disease , Phosphoenolpyruvate , Picrorhiza , Stearoyl-CoA Desaturase , Sterol Regulatory Element Binding Protein 1
18.
Article in English | WPRIM | ID: wpr-719218

ABSTRACT

Various endocrine dysfunctions occur during chemotherapy, including hypoglycemia. However, reports of hypoglycemia associated with 6-mercaptopurine (6-MP) are rare. Herein, we report an 8-year-old boy with severe symptomatic hypoglycemia likely due to 6-MP during chemotherapy. He had been diagnosed with acute lymphoblastic leukemia 3 years previously and was in the maintenance chemotherapy period. Treatment included oral dexamethasone, methotrexate, and 6-MP, of which only 6-MP was administered daily. Hypoglycemic symptoms appeared mainly at dawn, and his serum glucose dropped to a minimum of 37 mg/dL. Laboratory findings showed nothing specific other than increased serum cortisol, free fatty acids, ketone, alanine aminotransferase, and aspartate aminotransferase. Under the hypothesis of hypoglycemia due to chemotherapy drugs, we changed the time of 6-MP from evening to morning and recommended him to ingest carbohydrate-rich foods before bedtime. Hypoglycemia improved dramatically, and there was no further episode during the remaining maintenance chemotherapy period. To the best of our knowledge, this is the first report of this type of hypoglycemia occurring in an Asian child including Korean.


Subject(s)
Mercaptopurine , Alanine Transaminase , Asian Continental Ancestry Group , Aspartate Aminotransferases , Blood Glucose , Child , Dexamethasone , Drug Therapy , Fatty Acids, Nonesterified , Humans , Hydrocortisone , Hypoglycemia , Maintenance Chemotherapy , Male , Methotrexate , Precursor Cell Lymphoblastic Leukemia-Lymphoma
19.
Korean Journal of Medicine ; : 518-524, 2018.
Article in Korean | WPRIM | ID: wpr-718866

ABSTRACT

Hypertriglyceridemia a major cause of acute pancreatitis, accounting for up to 10% of all cases. The pathophysiological mechanism of hypertriglyceridemia-induced acute pancreatitis (HTGP) is presumed to involve the hydrolysis of triglycerides by pancreatic lipase resulting in an excess of free fatty acids and elevated chylomicrons, which are thought to increase plasma viscosity and induce ischemia and inflammation in pancreatic tissue. Although the clinical course of HTGP is similar to other forms of acute pancreatitis, the clinical severity and associated complications are significantly higher in patients with HTGP. Therefore, an accurate diagnosis is essential for treatment and prevention of disease recurrence. At present, there are no approved guidelines for the management of HTGP. Different treatment modalities such as apheresis/plasmapheresis, insulin, heparin, fibric acids, and omega-3 fatty acids have been successfully implemented to reduce serum triglycerides. Following acute phase management, lifestyle modifications including dietary adjustments and drug therapy are important for the long-term management of HTGP and the prevention of relapse. Additional studies are required to produce generalized and efficient treatment guidelines for HTGP.


Subject(s)
Chylomicrons , Diagnosis , Drug Therapy , Fatty Acids, Nonesterified , Fatty Acids, Omega-3 , Fibric Acids , Heparin , Humans , Hydrolysis , Hypertriglyceridemia , Inflammation , Insulin , Ischemia , Life Style , Lipase , Pancreatitis , Plasma , Recurrence , Triglycerides , Viscosity
20.
Article in English | WPRIM | ID: wpr-758807

ABSTRACT

The objective of this study was to compare ovulation rate, number of large ovarian follicles, and concentrations of plasma progesterone (P4) and non-esterified fatty acids (NEFA) between lame (n = 10) and non-lame (n = 10) lactating Holstein cows. The study was conducted in an organic dairy farm, and cows were evaluated by undertaking ultrasonography and blood sampling every 3 days from 30 days postpartum for a period of 34 days. Cows which became lame during the first 30 days postpartum experienced a lower ovulation rate determined by the presence of a corpus luteum (50% presence for lame cows and 100% for non-lame cows, p ≤ 0.05). The number of large ovarian follicles in the ovaries was 5 for lame cows and 7 for non-lame cows (p = 0.09). Compared to non-lame cows, lame cows had significantly lower (p ≤ 0.05) concentrations of plasma P4. Furthermore, NEFA concentrations were lower (p ≤ 0.05) in lame cows than in non-lame cows. It is concluded that lameness in postpartum dairy cows is associated with ovulation failure and lower concentrations of P4 and NEFA.


Subject(s)
Agriculture , Corpus Luteum , Fatty Acids , Fatty Acids, Nonesterified , Female , Mortuary Practice , Ovarian Follicle , Ovary , Ovulation , Plasma , Postpartum Period , Progesterone , Ultrasonography
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