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Sample records for involve liver muscle

  1. Liver involvement in systemic infection

    PubMed Central

    Minemura, Masami; Tajiri, Kazuto; Shimizu, Yukihiro

    2014-01-01

    The liver is often involved in systemic infections, resulting in various types of abnormal liver function test results. In particular, hyperbilirubinemia in the range of 2-10 mg/dL is often seen in patients with sepsis, and several mechanisms for this phenomenon have been proposed. In this review, we summarize how the liver is involved in various systemic infections that are not considered to be primarily hepatotropic. In most patients with systemic infections, treatment for the invading microbes is enough to normalize the liver function tests. However, some patients may show severe liver injury or fulminant hepatic failure, requiring intensive treatment of the liver. PMID:25276279

  2. Effect of dietary fish oil on the expression of genes involved in lipid metabolism in liver and skeletal muscle of lactating sows.

    PubMed

    Gessner, D K; Gröne, B; Rosenbaum, S; Most, E; Hillen, S; Becker, S; Erhardt, G; Reiner, G; Eder, K

    2016-04-01

    This study investigated the hypothesis that dietary supplementation of fish oil as a source of n-3 polyunsaturated fatty acids (PUFA) influences the expression of target genes of sterol regulatory element-binding proteins (SREBP)-1 and (SREBP)-2 involved in triacylglycerol (TAG) synthesis and fatty acid and cholesterol metabolism in the liver, and moreover activates the expression of target genes of peroxisome proliferation-activated receptor (PPAR)-α involved in TAG and fatty acid catabolism in liver and skeletal muscle. Twenty lactating sows were fed a control diet or a fish oil diet with either 50 g of a mixture of palm oil and soya bean oil (4:1, w/w) or fish oil per kg. The diet of the fish oil group contained 19.1 g of n-3 PUFA (mainly 20:5 n-3 and 22:6 n-3) per 100 g of total fatty acids, while the diet of the control group contained 2.4 g of n-3 PUFA (mainly 18:3 n-3) per 100 g of total fatty acids. The fish oil group had reduced relative mRNA concentrations of various target genes of SREBP-1 involved in fatty acid and TAG synthesis in comparison with the control group (p < 0.05). Relative mRNA concentrations of target genes of PPARα involved in fatty acid catabolism in both liver and muscle, and mRNA concentrations of target genes of SREBP-2 involved in cholesterol synthesis and uptake were not influenced by fish oil supplementation. Concentrations of cholesterol and TAG in plasma, fat content of milk and weight gains of litters during the suckling period were not different between the two groups of sows. In conclusion, this study suggests that fish oil has only minor effects on hepatic lipid metabolism, which are non-critical with respect to milk production in sows. PMID:25865806

  3. Malignant haemangioendothelioma involving the liver

    PubMed Central

    Pollard, Stella M.; Millward-Sadler, G. H.

    1974-01-01

    The features of four cases of malignant haemangioendothelioma involving the liver and other organs are described. Two cases were associated with a microangiopathic haemolytic anaemia. The nature of the tumours and possible pathogenesis for the anaemias are discussed. Images PMID:4832301

  4. Skeletal muscle involvement in cardiomyopathies.

    PubMed

    Limongelli, Giuseppe; D'Alessandro, Raffaella; Maddaloni, Valeria; Rea, Alessandra; Sarkozy, Anna; McKenna, William J

    2013-12-01

    The link between heart and skeletal muscle disorders is based on similar molecular, anatomical and clinical features, which are shared by the 'primary' cardiomyopathies and 'primary' neuromuscular disorders. There are, however, some peculiarities that are typical of cardiac and skeletal muscle disorders. Skeletal muscle weakness presenting at any age may indicate a primary neuromuscular disorder (associated with creatine kinase elevation as in dystrophinopathies), a mitochondrial disease (particularly if encephalopathy, ocular myopathy, retinitis, neurosensorineural deafness, lactic acidosis are present), a storage disorder (progressive exercise intolerance, cognitive impairment and retinitis pigmentosa, as in Danon disease), or metabolic disorders (hypoglycaemia, metabolic acidosis, hyperammonaemia or other specific biochemical abnormalities). In such patients, skeletal muscle weakness usually precedes the cardiomyopathy and dominates the clinical picture. Nevertheless, skeletal involvement may be subtle, and the first clinical manifestation of a neuromuscular disorder may be the occurrence of heart failure, conduction disorders or ventricular arrhythmias due to cardiomyopathy. ECG and echocardiogram, and eventually, a more detailed cardiovascular evaluation may be required to identify early cardiac involvement. Paediatric and adult cardiologists should be proactive in screening for neuromuscular and related disorders to enable diagnosis in probands and evaluation of families with a focus on the identification of those at risk of cardiac arrhythmia and emboli who may require specific prophylactic treatments, for example, pacemaker, implantable cardioverter-defibrillator and anticoagulation. PMID:24149064

  5. Respiratory involvement in inherited primary muscle conditions

    PubMed Central

    Shahrizaila, N; Kinnear, W J M; Wills, A J

    2006-01-01

    Patients with inherited muscle disorders can develop respiratory muscle weakness leading to ventilatory failure. Predicting the extent of respiratory involvement in the different types of inherited muscle disorders is important, as it allows clinicians to impart prognostic information and offers an opportunity for early interventional management strategies. The approach to respiratory assessment in patients with muscle disorders, the current knowledge of respiratory impairment in different muscle disorders and advice on the management of respiratory complications are summarised. PMID:16980655

  6. Lower Muscle Endurance in Patients with Alcoholic Liver Disease

    ERIC Educational Resources Information Center

    Andersen, Henning; Aagaard, Niels K.; Jakobsen, Johannes; Dorup, Inge; Vilstrup, Hendrik

    2012-01-01

    Patients with alcoholic liver disease often complain of restricted physical capacity, which could be due to decreased muscle endurance. The aim of this study was to assess the muscular endurance in patients with alcoholic liver disease. In a cross sectional study, 24 patients with alcoholic liver disease and 22 controls were evaluated using…

  7. Chronic exercise increases insulin binding in muscles but not liver.

    PubMed

    Bonen, A; Clune, P A; Tan, M H

    1986-08-01

    It has been postulated that the improved glucose tolerance provoked by chronic exercise is primarily attributable to increased insulin binding in skeletal muscle. Therefore, we investigated the effects of progressively increased training (6 wk) on insulin binding by five hindlimb skeletal muscles and in liver. In the trained animals serum insulin levels at rest were lower either in a fed (P less than 0.05) or fasted (P less than 0.05) state and after an oral glucose tolerance test (n = 8) (P less than 0.05). Twenty-four hours after the last exercise bout sections of the liver, soleus (S), plantaris (P), extensor digitorum longus (EDL), and red (RG) and white gastrocnemius (WG) muscles were pooled from four to six rats. From control animals, killed at the same time of day, muscles and liver were also obtained. Insulin binding to plasma membranes increased in S, P, and EDL (P less than 0.05) but not in WG (P = 0.07), RG (P greater than 0.1), or in liver (P greater than 0.1). There were insulin binding differences among muscles (P less than 0.05). Comparison of rank orders of insulin binding data with published glucose transport data for the same muscles revealed that these parameters do not correspond well. In conclusion, insulin binding to muscle is shown to be heterogeneous and training can increase insulin binding to selected muscles but not liver. PMID:3526921

  8. Liver involvement in adults with measles.

    PubMed

    Dinh, Aurélien; Fleuret, Victoire; Hanslik, Thomas

    2013-12-01

    We retrospectively collected the characteristics of 80 consecutive adult patients with biologically confirmed measles during a recent epidemic in France. We report on the frequency and severity of liver involvement in adult patients with measles. In our experience, measles in adults was not severe and hepatitis was not correlated with severe cases or bacterial infection. Therefore, hepatitis should be regarded as a usual symptom rather than a complication of measles infection in adults. PMID:23938044

  9. Differential isoform expression and selective muscle involvement in muscular dystrophies.

    PubMed

    Huovinen, Sanna; Penttilä, Sini; Somervuo, Panu; Keto, Joni; Auvinen, Petri; Vihola, Anna; Huovinen, Sami; Pelin, Katarina; Raheem, Olayinka; Salenius, Juha; Suominen, Tiina; Hackman, Peter; Udd, Bjarne

    2015-10-01

    Despite the expression of the mutated gene in all muscles, selective muscles are involved in genetic muscular dystrophies. Different muscular dystrophies show characteristic patterns of fatty degenerative changes by muscle imaging, even to the extent that the patterns have been used for diagnostic purposes. However, the underlying molecular mechanisms explaining the selective involvement of muscles are not known. To test the hypothesis that different muscles may express variable amounts of different isoforms of muscle genes, we applied a custom-designed exon microarray containing probes for 57 muscle-specific genes to assay the transcriptional profiles in sets of human adult lower limb skeletal muscles. Quantitative real-time PCR and whole transcriptome sequencing were used to further analyze the results. Our results demonstrate significant variations in isoform and gene expression levels in anatomically different muscles. Comparison of the known patterns of selective involvement of certain muscles in two autosomal dominant titinopathies and one autosomal dominant myosinopathy, with the isoform and gene expression results, shows a correlation between the specific muscles involved and significant differences in the level of expression of the affected gene and exons in these same muscles compared with some other selected muscles. Our results suggest that differential expression levels of muscle genes and isoforms are one determinant in the selectivity of muscle involvement in muscular dystrophies. PMID:26269091

  10. Sex-specific divergence of antioxidant pathways in fetal brain, liver, and skeletal muscles.

    PubMed

    Al-Gubory, Kaïs H; Garrel, Catherine

    2016-01-01

    The sex-specific divergence of antioxidant pathways in fetal organs of opposite-sex twin is unknown and remains urgently in need of investigation. Such study faces many challenges, mainly the ethical impossibility of obtaining human fetal organs. Opposite-sex sheep twins represent a unique model for studying a sex dimorphism for antioxidant systems. The activity of total superoxide dismutase (SOD), SOD1, SOD2, glutathione peroxidase (GPX), glutathione reductase (GR) and catalase (CAT), the content of total glutathione, reduced glutathione (GSH), and oxidized glutathione (GSSG) were measured in brain, lung, liver, kidney, and skeletal muscles of female and male fetuses collected from sheep twin pregnancies at day 65 of gestation. Lipid peroxidation was assessed by measuring melondialdehyde (MDA) tissue content. Male brain has greater total SOD and SOD1 activities than female brain. Female liver has greater SOD2 activity than male liver. Male liver has greater GR activity than female liver. Male liver has higher total GSH and GSSG content than female liver. Male skeletal muscles have higher total GSH, GSH, and GSSG content than female skeletal muscles. Female brain and liver have higher MDA content than male brain and liver. This is the first report of a sex dimorphism for fetal organ antioxidative pathways. Brain, liver, and skeletal muscles of male and female fetuses display distinct antioxidant pathways. Such sexually dimorphic responses to early life oxidative stress might be involved in the sex-related difference in fetal development that may have a long-term effect on offspring. Our study urges researchers to take into consideration the importance of sex as a biologic variable in their investigations. PMID:26765668

  11. Growth factor involvement in tension-induced skeletal muscle growth

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman H.

    1993-01-01

    Long-term manned space travel will require a better understanding of skeletal muscle atrophy which results from microgravity. Astronaut strength and dexterity must be maintained for normal mission operations and for emergency situations. Although exercise in space slows the rate of muscle loss, it does not prevent it. A biochemical understanding of how gravity/tension/exercise help to maintain muscle size by altering protein synthesis and/or degradation rate should ultimately allow pharmacological intervention to prevent muscle atrophy in microgravity. The overall objective is to examine some of the basic biochemical processes involved in tension-induced muscle growth. With an experimental in vitro system, the role of exogenous and endogenous muscle growth factors in mechanically stimulated muscle growth are examined. Differentiated avian skeletal myofibers can be 'exercised' in tissue culture using a newly developed dynamic mechanical cell stimulator device which simulates different muscle activity patterns. Patterns of mechanical activity which significantly affect muscle growth and metabolic characteristics were found. Both exogenous and endogenous growth factors are essential for tension-induced muscle growth. Exogenous growth factors found in serum, such as insulin, insulin-like growth factors, and steroids, are important regulators of muscle protein turnover rates and mechanically-induced muscle growth. Endogenous growth factors are synthesized and released into the culture medium when muscle cells are mechanically stimulated. At least one family of mechanically induced endogenous factors, the prostaglandins, help to regulate the rates of protein turnover in muscle cells. Endogenously synthesized IGF-1 is another. The interaction of muscle mechanical activity and these growth factors in the regulation of muscle protein turnover rates with our in vitro model system is studied.

  12. Chemokine receptor CCR2 involvement in skeletal muscle regeneration.

    PubMed

    Warren, Gordon L; Hulderman, Tracy; Mishra, Dawn; Gao, Xin; Millecchia, Lyndell; O'Farrell, Laura; Kuziel, William A; Simeonova, Petia P

    2005-03-01

    Chemokines, signaling through the CCR2 receptor, are highly expressed in injured skeletal muscle. Their target specificity depends on the cellular expression of the specific receptors. Here we demonstrate that, in freeze-injured muscle, CCR2 co-localized with Mac-3, a marker of activated macrophages as well as with myogenin, a marker of activated muscle precursor cells. The degeneration/regeneration process in skeletal muscle of CCR2-/- and wild-type mice was not significantly different at day 3. However in contrast to the regenerated muscle of the wild-type mice, the muscle from CCR2-/- mice was characterized by impaired regeneration, inflammation, and fibrotic response at day 14, increased fat infiltration, fibrosis, and calcification at day 21, and impaired strength recovery until at least 28 days post-injury. Consistently, the increased expression of Mac-1 and TNF-alpha was prolonged in the injured muscle of CCR2-/- mice. The expression pattern of the myogenic factors MyoD and myogenin was similar for both types of mice, while NCAM, which is associated with the initiation of fusion of muscle precursor cells, was more increased in the injured muscle of CCR2-/- mice. In conclusion, the study delineates that signaling through CCR2 is involved in muscle precursor cell activities necessary for complete and rapid regeneration of injured skeletal muscle. PMID:15601671

  13. Liver, but Not Muscle, Has an Entrainable Metabolic Memory

    PubMed Central

    Mulligan, Kimberly X.; Lundblad, Tammy M.; Williams, Phillip E.; McGuinness, Owen P.

    2014-01-01

    Hyperglycemia in the hospitalized setting is common, especially in patients that receive nutritional support either continuously or intermittently. As the liver and muscle are the major sites of glucose disposal, we hypothesized their metabolic adaptations are sensitive to the pattern of nutrient delivery. Chronically catheterized, well-controlled depancreatized dogs were placed on one of three isocaloric diets: regular chow diet once daily (Chow) or a simple nutrient diet (ND) that was given either once daily (ND-4) or infused continuously (ND-C). Intraportal insulin was infused to maintain euglycemia. After 5 days net hepatic (NHGU) and muscle (MGU) glucose uptake and oxidation were assessed at euglycemia (120 mg/dl) and hyperglycemia (200 mg/dl) in the presence of basal insulin. While hyperglycemia increased both NHGU and MGU in Chow, NHGU was amplified in both groups receiving ND. The increase was associated with enhanced activation of glycogen synthase, glucose oxidation and suppression of pyruvate dehydrogenase kinase-4 (PDK-4). Accelerated glucose-dependent muscle glucose uptake was only evident with ND-C. This was associated with a decrease in PDK-4 expression and an increase in AMP-activated protein kinase (AMPK) phosphorylation. Interestingly, ND-C markedly increased hepatic FGF-21 expression. Thus, augmentation of carbohydrate disposal in the liver, as opposed to the muscle, is not dependent on the pattern of nutrient delivery. PMID:24465939

  14. Dissociated lower limb muscle involvement in amyotrophic lateral sclerosis.

    PubMed

    Simon, Neil G; Lee, Michael; Bae, Jong Seok; Mioshi, Eneida; Lin, Cindy S-Y; Pfluger, Casey M; Henderson, Robert D; Vucic, Steve; Swash, Michael; Burke, David; Kiernan, Matthew C

    2015-06-01

    It has been suggested that corticomotoneuronal drive to ankle dorsiflexors is greater than to ankle plantar flexor muscles, despite the finding that plantar flexors are no less active than TA during walking and standing. The present study was undertaken to determine whether there was differential involvement of distal lower limb muscles in amyotrophic lateral sclerosis (ALS), to elucidate pathophysiological mechanisms of selective muscle involvement. Prospective studies were undertaken in 52 ALS patients, including clinical assessment, disease staging (revised ALS functional rating scale), Medical Research Council sum score, and a scale of upper motor neurone (UMN) dysfunction. Motor unit number estimates (MUNE) and compound muscle action potentials (CMAP) from ankle dorsiflexors and plantar flexors were used to provide objective measures. A novel 'split leg index' was calculated as follows: SLI = CMAPDF ÷ CMAPPF. In ALS, there was significantly greater reduction of MUNE and CMAP amplitude recorded from plantar flexors when compared to dorsiflexors, suggesting preferential involvement of plantar flexor muscles, underpinning a 'split leg' appearance. The SLI correlated with clinical plantar flexor strength (R= -0.56, p < 0.001). In no patient did the SLI suggest preferential dorsiflexor involvement. In subgroup analyses, mean SLI was greatest in lower limb-onset ALS. In conclusion, the present study has established dissociated involvement of muscles acting around the ankle in ALS. We suggest this reflects underlying differences in cortical, descending or local spinal modulation of these muscles. PMID:25845764

  15. A second MNGIE patient without typical mitochondrial skeletal muscle involvement.

    PubMed

    Cardaioli, Elena; Da Pozzo, Paola; Malfatti, Edoardo; Battisti, Carla; Gallus, Gian Nicola; Gaudiano, Carmen; Macucci, Marco; Malandrini, Alessandro; Margollicci, Maria; Rubegni, Anna; Dotti, Maria Teresa; Federico, Antonio

    2010-08-01

    Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disease caused by mutations in the gene encoding thymidine phosphorylase (TYMP). Clinically, MNGIE is characterized by gastrointestinal dysmotility, cachexia, ptosis, ophthalmoparesis, peripheral neuropathy and leukoencephalopathy. Most MNGIE patients have signs of mitochondrial dysfunction in skeletal muscle at morphological and enzyme level, as well as mitochondrial DNA depletion, multiple deletions and point mutations. A case without mitochondrial skeletal muscle involvement and with a TYMP splice-acceptor site mutation (c. 215-1 G>C) has been reported. Here, we describe an Italian patient with the same mutation and without mitochondrial skeletal muscle involvement, suggesting a possible genotype-phenotype correlation. PMID:20232099

  16. Relationships between organochlorine concentrations in liver and muscle of otters

    SciTech Connect

    Mason, C.F. )

    1989-10-01

    The European otter (Lutra lutra) is now threatened or endangered over much of its European range. The decline, which has taken place mainly during the past three decades, has been attributed to the toxic effects of organochlorine residues, with emphasis being placed on dieldrin or PCBs. Few otters were analyzed for organochlorines during the main period of decline but there is not considerable interest in the species. Experiments with ranch mink (Mustela vison) have shown that reproductive failure occurs when PCB concentrations in thigh muscle approach 50 mg kg{sup {minus}1} lipid. Because otters are closely related and have similar habits this value is becoming widely used to interpret the potential significance of PCB concentrations determined in otters. Furthermore, although the mink data refer to concentrations in muscle, interpretations of concentrations in otters have frequently been based on analyses of livers. Because of the diverse sources of material in Europe, only limited tissues may be made available for analysis, while costs may also prohibit the analysis of several tissues from a single carcass. The relationship between concentrations of organochlorines in muscle and liver tissues in otters has not been determined. This is the purpose of the present communication.

  17. Involvement of liver in diabetes mellitus: herbal remedies.

    PubMed

    Thent, Z C; Das, S

    2014-01-01

    Liver disease is considered as one of the major complications in oxidative stress disorders like diabetes mellitus (DM). DM presents with deterioration in carbohydrate metabolism which is characterized with chronic hyperglycemia. The organ which involves in glucose or carbohydrate metabolism and is most likely to be affected is the liver. Deterioration in liver architecture and metabolism in DM, are considered as common findings. In the present review both biochemical and histological changes occurring in diabetic liver are conferred in detail. To counteract the oxidative stress disorders and its untoward complications, antioxidant or herbs have emerged as alternative medicine. The present review focuses on several herbs with antioxidant properties towards diabetic liver disease such as Liquorice, Pelargonium gravenolens, Momordica charantia, Propolis from bee hives, Dihar, Curcuma Longa, Tinospora cordifolia, Kangen-karyu, Parsley, Chard, Green tea Catechins and Piper sarmentosum (P.s). The herbs or the compounds present in herbs have potential to improve the liver metabolism and maintain the integrity of liver tissue in DM. The review also opens the door for effective use of herbal products for complications involved in the diabetic liver disease. PMID:25203338

  18. Mercury concentrations in muscle and liver tissue of fish from marshes along the Magdalena River, Colombia.

    PubMed

    Alvarez, Santiago; Kolok, Alan S; Jimenez, Luz Fernanda; Granados, Carlos; Palacio, Jaime A

    2012-10-01

    The present research determined the total mercury concentrations in muscle and liver tissue in fish collected from the Magdalena River watershed. A total of 378 muscle samples and 102 liver samples were included in the analysis. The highest mean mercury level in muscle tissue was found in the noncarnivore, Pimelodus blochii. However, as a group, carnivores had significantly higher (p < 0.05) mercury levels in their muscle tissue than noncarnivores. A significant correlation (p < 0.05) was obtained between fish mass and mercury concentrations in muscle or liver in four species. No differences were observed in total mercury concentration based either on species or gender. PMID:22923139

  19. Liver involvement of Langerhans’ cell histiocytosis in children

    PubMed Central

    Yi, Xiaoping; Han, Tong; Zai, Hongyan; Long, Xueying; Wang, Xiaoyi; Li, Wenzheng

    2015-01-01

    Objective: Liver involvement is relatively frequent in children with Langerhans cell histiocytosis (LCH). Its features remain poorly defined. Methods: A retrospective study was carried out on 14 hepatic LCH children in our hospital. The Clinicopathological and radiological features of this disease was discussed. Results: The rate of liver involvement in children LCH patients is 51.9%. Majority of the patients were disseminated cases. Hepatomegaly was clinically confirmed in 11 cases (78.6%). Liver function dysfunction was seen in nine (64.3%) children. The association of multi-modal imaging significantly yielded more diagnostic information. There are some imaging characteristics of this disease, CT and MRI could help to assess the staging, extent of the hepatic lesions. We found that liver involvement had a significant impact on survival. Patients treated with systemic chemotherapy earlier from time of diagnosis had a relatively better outcome. Conclusions: The rate of liver involvement in children LCH patients maybe much higher than that of expected. We suggest that clinical and biological liver evaluation and abdominal imaging must be performed regularly onwards to screen every LCH children patient from the time of the initial diagnosis. Patient should be treated with systemic chemotherapy earlier. PMID:26221247

  20. Liver involvement in HIV-infected patients with early syphilis.

    PubMed

    Palacios, R; Navarro, F; Narankiewicz, D; Marcos, M; Jiménez-Oñate, F; de la Torre, J; Santos, J

    2013-01-01

    The aim of the paper is to analyse the prevalence of liver involvement and related factors in HIV-infected patients with early syphilis (<2 years). Liver involvement was defined as an elevation above normal ranges of alanine transaminase, aspartate aminotransferase, gamma-glutamyltransferase and/or alkaline phosphatase during early syphilis, or doubling of previous levels in patients with liver enzyme elevation before syphilis. We undertook a multicentre study and of the 147 cases, 86.4% were men who had sex with men, and the diagnoses of syphilis and HIV infection were coincident in 48 (32.7%). Liver involvement was detected in 45 (30.6%) and the only related factor was a rapid plasma reagin (RPR) titre ≥1/64 (odds ratio 3.76; 95% confidence interval 1.3-10.5; P = 0.012). In conclusion, liver involvement occurs in around one-third of HIV-infected patients with early syphilis and is associated with high RPR levels. Syphilis should be included in the differential diagnosis of liver enzyme elevation in HIV-infected patients. PMID:23467288

  1. Nerve and muscle involvement in mitochondrial disorders: an electrophysiological study.

    PubMed

    Mancuso, Michelangelo; Piazza, Selina; Volpi, Leda; Orsucci, Daniele; Calsolaro, Valeria; Caldarazzo Ienco, Elena; Carlesi, Cecilia; Rocchi, Anna; Petrozzi, Lucia; Calabrese, Rosanna; Siciliano, Gabriele

    2012-04-01

    Involvement of the peripheral nervous system in mitochondrial disorders (MD) has been previously reported. However, the exact prevalence of peripheral neuropathy and/or myopathy in MD is still unclear. In order to evaluate the prevalence of neuropathy and myopathy in MD, we performed sensory and motor nerve conduction studies (NCS) and concentric needle electromyography (EMG) in 44 unselected MD patients. NCS were abnormal in 36.4% of cases, and were consistent with a sensori-motor axonal multineuropathy (multifocal neuropathy), mainly affecting the lower limbs. EMG evidence of myopathy was present in 54.5% of patients, again mainly affecting the lower limbs. Nerve and muscle involvement was frequently subclinical. Peripheral nerve and muscle involvement is common in MD patients. Our study supports the variability of the clinical expression of MD. Further studies are needed to better understand the molecular basis underlying the phenotypic variability among MD patients. PMID:21751099

  2. Impact of muscle wasting on survival in patients with liver cirrhosis.

    PubMed

    Kalafateli, Maria; Konstantakis, Christos; Thomopoulos, Konstantinos; Triantos, Christos

    2015-06-28

    Muscle wasting is defined as the progressive and generalized loss of muscle mass. Muscle depletion is a common feature of chronic liver disease found in approximately 40% of patients with cirrhosis. Its etiology is multifactorial subsequent to liver failure and its prevalence increases along with disease severity. Cross-sectional analytic morphometry using computed tomography (CT) scan or magnetic resonance imaging are considered by consensus the gold standards to assess muscle size in cirrhosis for research purposes because they are not biased by fluid accumulation. Several studies have assessed the impact of muscle wasting on overall survival of patients in the waiting list for liver transplantation and there is a general agreement that decreased muscle size assessed by CT scan is an independent predictor for mortality in cirrhosis. It has been proposed that the addition of cross-sectional muscle area into the Model for End-stage Liver Disease can increase its prognostic performance. Nevertheless, the use of CT scan in assessing muscle size is inappropriate for routine clinical practice and an alternative cost-effective, easy to use and accurate tool should be developed. In conclusion, muscle wasting has a detrimental impact on survival of patients with cirrhosis and, thus, it remains to be elucidated if nutritional interventions and exercise could improve muscle wasting and, subsequently, survival in this setting. PMID:26139982

  3. Involvement of constitutive androstane receptor in liver hypertrophy and liver tumor development induced by triazole fungicides.

    PubMed

    Tamura, Kei; Inoue, Kaoru; Takahashi, Miwa; Matsuo, Saori; Irie, Kaoru; Kodama, Yukio; Gamo, Toshie; Ozawa, Shogo; Yoshida, Midori

    2015-04-01

    We clarified the involvement of constitutive androstane receptor (CAR) in triazole-induced liver hypertrophy and tumorigenesis using CAR-knockout (CARKO) mice. Seven-week-old male CARKO and wild-type (WT) mice were treated with 200 ppm cyproconazole (Cypro), 1500 ppm tebuconazole (Teb), or 200 ppm fluconazole (Flu) in the diet for 27 weeks after initiation by diethylnitrosamine (DEN). At weeks 4 (without DEN) and 13 (with DEN), WT mice in all treatment groups and CARKO mice in Teb group revealed liver hypertrophy with mainly Cyp2b10 and following Cyp3a11 inductions in the liver. Teb also induced Cyp4a10 in both genotypes. Cypro induced slight and duration-dependent liver hypertrophy in CARKO mice. At week 27, Cypro and Teb significantly increased eosinophilic altered foci and/or adenomas in WT mice. These proliferating lesions were clearly reduced in CARKO mice administered both compounds. The eosinophilic adenomas caused by Flu decreased in CARKO mice. The present study indicates that CAR is the main mediator of liver hypertrophy induced by Cypro and Flu, but not Teb. In contrast, CAR played a crucial role in liver tumor development induced by all three triazoles. PMID:25656644

  4. Enzyme activities in plasma, kidney, liver, and muscle of five avian species

    USGS Publications Warehouse

    Franson, J.C.; Murray, H.C.; Bunck, C.

    1985-01-01

    Activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatine phosphokinase (CPK), and lactate dehydrogenase (LDH) were determined in plasma, kidney, liver, and muscle from five species of captive birds. Few differences occurred in plasma activities between sexes but considerable differences occurred between species. All five enzymes were detected in each of the tissues sampled. Relative enzyme activities in liver, kidney, and muscle were similar for each species. CPK activity was much higher in muscle than in liver or kidney and, of the five enzymes studied, may be the best indicator of muscle damage. Most of the other enzymes were more evenly distributed among the three tissues, and no organ-specific enzyme could be identified for liver or kidney. Because of interspecific variations in plasma enzyme activities, it is important to establish baseline values for each species to ensure accurate interpretation of results.

  5. Structural differences between liver- and muscle-derived insulin receptors in rats

    SciTech Connect

    Burant, C.F.; Treutelaar, M.K.; Block, N.E.; Buse, M.G.

    1986-11-05

    The structure of insulin receptors, solubilized from rat skeletal muscle and liver, was studied. The ..cap alpha.. subunit was identified by specific cross-linking to A14 /sup 125/I-insulin with disuccinimidyl suberate. Muscle- and liver-derived ..cap alpha.. subunits migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with a M/sub r/ of 131,000 and 135,000, respectively. There was no significant difference in insulin binding affinity. Treatment of cross-linked, immunoprecipitated receptors with either neuraminidase or endoglycosidase H decreased the M/sub r/ of muscle- and liver-derived ..cap alpha.. subunits but did not affect the difference in M/sub r/. Autophosphorylated ..beta.. subunits migrated with a M/sub r/ of 98,000 for muscle and 101,000 for liver. After partial V8 digestion of autophosphorylated, immunoprecipitated receptors the major phosphopeptide fragment migrated on SDS-PAGE at M/sub r/ 57,000 from muscle and 60,000 from liver. Glycosidase digestion of autophosphorylated receptors suggested that M/sub r/ heterogeneity was due in part to differences in the sialic acid content of ..beta.. subunits. Muscle and liver are the major target organs of insulin; the apparent heterogeneity of insulin receptor structure may be relevant to tissue-specific differences in insulin action.

  6. [Juvenile xanthogranuloma. Description of a case with liver involvement].

    PubMed

    Di Blasi, A; de Seta, L; Marsilia, G M; Coletta, S; Siani, P; de Rosa, I

    1993-01-01

    Juvenile Xanthogranuloma. Report of a case with hepatic involvement. The Authors present a case of Juvenile Xanthogranuloma (JX) in a 3 months female child with cutaneous and hepatic nodules associated to dyspnea attributable to obstructive bronchopneumopathy. Histologically the lesions are xanthomatous with proliferation of fat-laden histiocytes. The hepatic involvement is characterized by hepatomegaly and yellow nodules on liver surface as seen at laparoscopy. On liver biopsy there is remarkable expansion of portal triad caused by aggregates of large foamy mono-polynuclear histiocytes with Touton giant cells. The cutaneous nodule biopsy shows histiocytic infiltrate in inter-adnexal dermal space with many giant cells holding great lipidic vacuoles. The patient's follow-up is characterized by slow and progressive clinical improvement with resolution of cutaneous, hepatic and pulmonary pathology. The Authors emphasize the differential diagnosis between this systemic form of JX and Langerhans cell Histiocytosis (Histiocytosis X) with multiorgan involvement. This diagnosis is necessary in order to establish therapy and prognosis. PMID:8516025

  7. Expression profile of IGF paralog genes in liver and muscle of a GH-transgenic zebrafish.

    PubMed

    Nornberg, Bruna Felix; Figueiredo, Marcio Azevedo; Marins, Luis Fernando

    2016-01-15

    The objective of this study was to investigate the relationship between IGFs produced in the liver and skeletal muscle with muscle hypertrophy previously observed in a line of GH-transgenic zebrafish. In this sense, we evaluated the expression of genes related to the IGF system in liver and muscle of transgenics, as well as the main intracellular signaling pathways used by GH/IGF axis. Our results showed an increase in expression of igf1a, igf2a, and igf2b genes in the liver. Moreover, there was a decrease in the expression of igf1ra and an increase in muscle igf2r of transgenics, indicating a negative response of muscle tissue with respect to excess circulating IGFs. Muscle IGFs expression analyses revealed a significant increase only for igf2b, accompanied by a parallel induction of igfbp5a gene. The presence of IGFBP5a may potentiate the IGF2 action in muscle cells differentiation. Regarding JAK/STAT-related genes, we observed an alteration in the expression profile of both stat3 and stat5a in transgenic fish liver. No changes were observed in the muscle, suggesting that both tissues respond differently to GH-transgenesis. Western blotting analyses indicated an imbalance between the phosphorylation levels of the proliferative (MEK/ERK) and hypertrophic (PI3K/Akt) pathways, in favor of the latter. In summary, the results of this study suggest that the hypertrophy caused by GH-transgenesis in zebrafish may be due to circulating IGFs produced by the liver, with an important participation of muscle IGF2b. This group of IGFs appears to be favoring the hypertrophic intracellular pathway in muscle tissue of transgenic zebrafish. PMID:26718079

  8. Altered feeding differentially regulates circadian rhythms and energy metabolism in liver and muscle of rats.

    PubMed

    Reznick, Jane; Preston, Elaine; Wilks, Donna L; Beale, Susan M; Turner, Nigel; Cooney, Gregory J

    2013-01-01

    Energy metabolism follows a diurnal pattern responding to the light/dark cycle and food availability. This study investigated the impact of restricting feeding to the daylight hours and feeding a high fat diet on circadian clock (bmal1, dbp, tef and e4bp4) and metabolic (pepck, fas, ucp3, pdk4) gene expression and markers of energy metabolism in muscle and liver of rats. The results show that in chow-fed rats switched to daylight feeding, the peak diurnal expression of genes in liver was shifted by 6-12h while expression of these genes in muscle remained in a similar phase to rats feeding ad libitum. High fat feeding during the daylight hours had limited effect on clock gene expression in liver or muscle but shifted the peak expression of metabolic genes (pepck, fas) in liver by 6-12h. The differential effects of daylight feeding on gene and protein expression in muscle and liver were accompanied by an 8% reduction in whole body energy expenditure, a 20-30% increased glycogen content during the light phase in muscle of day-fed rats and increased adipose tissue deposition per gram food consumed. These data demonstrate that a mismatch of feeding and light/dark cycle disrupts tissue metabolism in muscle with significant consequences for whole body energy homeostasis. PMID:22952003

  9. Total mercury in liver and muscle tissue of two coastal sharks from the northwest of Mexico.

    PubMed

    Hurtado-Banda, Rocío; Gomez-Alvarez, Agustín; Márquez-Farías, J Fernando; Cordoba-Figueroa, Marcial; Navarro-García, Gerardo; Medina-Juárez, Luis Angel

    2012-06-01

    Total mercury (THg) in liver and muscle of three costal sharks from Mexico were evaluated. The highest concentrations of THg in muscle tissue of juveniles were found in Sphyrna lewini (0.82 ± 0.33 mg kg(-1) wet basis). Rhizoprionodon longurio adults had the highest concentrations (0.92 ± 1.03 mg kg(-1)). THg concentrations in liver were low compared to those found in muscle tissue; higher levels were found in liver of juvenile S. lewini (0.250 ± 0.07 mg kg(-1)). Results showed that 35 % of muscle tissue samples are above the precautionary limit (0.50 mg kg(-1) of THg) and a 7 % exceeded the maximum limit for human consumption (1 mg kg(-1)). PMID:22526987

  10. Mercury in muscle and liver of ten ray species from Northwest Mexico.

    PubMed

    Ruelas-Inzunza, J; Escobar-Sánchez, O; Patrón-Gómez, J; Moreno-Sánchez, X G; Murillo-Olmeda, A; Spanopoulos-Hernández, M; Corro-Espinosa, D

    2013-12-15

    We determined total mercury (Hg) distribution in muscle and liver of ten ray species and assessed health risk considering Hg levels in muscle and average consumption of rays in Mexico. Rays were collected from five sites in NW Mexico between March and November 2012. Hg concentrations ranged from 4.465 μg g(-1) in muscle of the longtail stingray Dasyatis longa to 0.036 μg g(-1) in liver of the diamond stingray Dasyatis dipterura. Considering all the individuals, Hg in muscle (1.612±1.322 μg g(-1)) was significantly (p<0.05) higher than in liver (0.745±0.616 μg g(-1)). Regarding local health risk assessment, none of the ray species may cause adverse effects on consumers. PMID:24074639

  11. Growth factor involvement in tension-induced skeletal muscle growth

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman W.

    1987-01-01

    New muscle tissue culture techniques were developed to grow embryonic skeletal myofibers which are able to differentiate into more adultlike myofibers. Studies on mechanical simulation of cultured muscle cell growth will now be more directly applicable to mechanically-induced growth in adult muscle, and lead to better models for understanding muscle tissue atrophy caused by disuse in the microgravity of space.

  12. Growth factor involvement in tension-induced skeletal muscle growth

    NASA Technical Reports Server (NTRS)

    Vandenburgh, H. H.

    1987-01-01

    Muscle tissue culture techniques were developed to grow skeletal myofibers which differentiate into more adult-like myofibers. Mechanical simulation studies of these muscle cells in a newly developed mechanical cell simulator can now be performed to study growth processes in skeletal muscle. Conditions in the mechanical cell simulator were defined where mechanical activity can either prevent muscle wasting or stimulate muscle growth. The role of endogenous and exogenous growth factors in tension-induced muscle growth is being investigated under the defined conditions of tissue culture.

  13. Muscles involved in naris dilation and nose motion in rat

    PubMed Central

    Deschênes, Martin; Haidarliu, Sebastian; Demers, Maxime; Moore, Jeffrey; Kleinfeld, David; Ahissar, Ehud

    2016-01-01

    In a number of mammals muscle dilator nasi (naris) is known as a muscle that reduces nasal airflow resistance by dilating the nostrils. Here we show that in rats the tendon of this muscle inserts into the aponeurosis above the nasal cartilage. Electrical stimulation of this muscle lifts the nose and deflects it sideway towards the side of stimulation, but does not change the size of the nares. In the head-fixed alert rat, electromyographic activity of muscle dilator nasi is tightly coupled to nose motion, not to opening of the nares. Yet, contraction of muscle dilator nasi occurs during the pre-inspiratory phase of the respiratory cycle, suggesting a role in sniffing and sampling odorants. We also show that opening of the nares results from contraction of pars maxillaris profunda of the muscle nasolabialis profundus. This muscle attaches to the outer wall of the nasal cartilage and to the plate of the mystacial pad. Contraction of this muscle exerts a dual action: it pulls the lateral nasal cartilage outwardly, thus dilating the naris, and it drags the plate of the mystacial pad rostralward, provoking a slight retraction of the whiskers. On the basis of these results, we propose that muscle dilator nasi of the rat be renamed muscle deflector nasi, and that pars maxillaris profunda of the muscle nasolabialis profundus be named muscle dilator nasi. PMID:25257748

  14. The assessment of trace metals at gill, muscle and liver tissue in Mugil cephalus.

    PubMed

    Engin, Mehmet Soner

    2015-05-01

    In this paper, concentrations of trace metals such as Cr, Mn, Fe, Ni, Cu, As, Se, Ag, Cd and Pb were determined in Mugil cephalus of the middle Black Sea coasts by employing inductively coupled plasma mass spectrometry (ICP-MS) and microwave digestion technique. Different parts of fish samples were analysed separately such as the gill, muscle and liver. The accuracy of the results has been checked by using a certified reference material (DORM-4). The highest trace metal values determined in different parts of fish were Cr in muscle tissue (0.416 μg/g), Mn in gill tissue (52.246 μg/g), Fe in muscle tissue (11.899 μg/g), Ni in muscle tissue (108.057 μg/g), Cu in liver tissue (261.911 μg/g), As in liver tissue (4.162 μg/g), Se in liver tissue (11.418 μg/g), Ag in liver tissue (0.323 μg/g), Cd in liver tissue (1.11 μg/g) and Pb in gill tissue (3.047 μg/g). These results were also compared with various relevant literature and guidelines. PMID:25877641

  15. Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

    PubMed

    Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

    2015-01-01

    In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type. PMID:25198797

  16. Enzymatic hydrolysis of starry triggerfish (Abalistes stellaris) muscle using liver proteinase from albacore tuna (Thunnus alalunga).

    PubMed

    Sripokar, P; Chaijan, M; Benjakul, S; Kishimura, H; Klomklao, S

    2016-02-01

    Proteinases from liver extract from albacore tuna (Thunnus alalunga) were used to produce protein hydrolysate from starry triggerfish (Abalistes stellaris) muscle. Hydrolysis conditions for preparing protein hydrolysate from starry triggerfish muscle were optimized. Enzyme level, reaction time and fish muscle/buffer ratio significantly affected the hydrolysis (p < 0.05). Optimum conditions for triggerfish muscle hydrolysis were 5.5 % liver extract, 40 min reaction time and fish muscle/buffer ratio of 1:3 (w/v). The freeze-dried protein hydrolysate was characterized with respect to chemical composition, amino acid composition and color. The product contained 91.73 % protein, 2.04 % lipid and 6.48 % ash. The protein hydrolysate exhibited high amount of essential amino acids (45.62 %). It was light yellow in color (L (*) = 82.94, a (*) = 0.84, b (*) = 22.83). The results indicate that the extract from liver of albacore tuna could be used to produce fish protein hydrolysate and protein hydrolysate from starry triggerfish muscle may potentially serve as a good source of desirable peptide and amino acids. PMID:27162384

  17. Sequence differences between human muscle and liver cDNAs for UDPglucose pyrophosphorylase and kinetic properties of the recombinant enzymes expressed in Escherichia coli.

    PubMed

    Duggleby, R G; Chao, Y C; Huang, J G; Peng, H L; Chang, H Y

    1996-01-15

    UDP-Glc pyrophosphorylase (EC 2.7.7.9) catalyses the interconversion of MgUTP plus Glc1P and UDP-Glc plus MgPPi. Complementation of an Escherichia coli strain lacking this activity has allowed isolation of cDNA encoding this enzyme from a human muscle library. Two forms were identified and the nucleotide sequence of each was determined; they were found to differ only in the 5' region and we suggest that these arise from the use of a different first exon in the two transcripts. These nucleotide sequences are different from that of the cDNA which was isolated previously from a human liver library [Peng, H.-L. & Chang, H.-Y. (1993) FEBS Lett. 329, 153-158] and it is proposed that these liver and muscle forms are derived from different genes. The cDNA for muscle form I, muscle form II, the liver form, and the liver form fused to part of the lacZ gene were expressed in Escherichia coli and the kinetic properties of each enzyme were characterised. Muscle form I and the LacZ/liver fusion enzyme exhibit Michaelis-Menten kinetics towards all substrates while muscle form II has a sigmoidal dependence of rate upon the concentration of MgPPi. The liver form shows Michaelis-Menten kinetics towards MgUTP. For the remaining three substrates, complex kinetics were observed involving a combination of sigmoidicity at low substrate concentration and partial inhibition at high substrate concentration. PMID:8631325

  18. Sarcopenia and liver transplant: The relevance of too little muscle mass

    PubMed Central

    Kallwitz, Eric R

    2015-01-01

    Loss of muscle mass and function is a common occurrence in both patients with decompensated cirrhosis and those undergoing liver transplantation. Sarcopenia is associated with morbidity and mortality before and after liver transplantation. The ability of skeletal muscle mass to recover after transplant is questionable, and long term adverse events associated with persistent sarcopenia have not been well studied. Limited data is available examining mechanisms by which decreased muscle mass might develop. It is not clear which interventions might reduce the prevalence of sarcopenia and associated health burdens. However, measures to either decrease portal hypertension or improve nutrition appear to have benefit. Research on sarcopenia in the liver transplant setting is hampered by differing methodology to quantify muscle mass and varied thresholds determining the presence of sarcopenia. One area highlighted in this review is the heterogeneity used when defining sarcopenia. The health consequences, clinical course and potential pathophysiologic mechanisms of sarcopenia in the setting of cirrhosis and liver transplantation are further discussed. PMID:26494955

  19. Thermal manipulation during embryogenesis has long-term effects on muscle and liver metabolism in fast-growing chickens.

    PubMed

    Loyau, Thomas; Métayer-Coustard, Sonia; Berri, Cécile; Crochet, Sabine; Cailleau-Audouin, Estelle; Sannier, Mélanie; Chartrin, Pascal; Praud, Christophe; Hennequet-Antier, Christelle; Rideau, Nicole; Couroussé, Nathalie; Mignon-Grasteau, Sandrine; Everaert, Nadia; Duclos, Michel Jacques; Yahav, Shlomo; Tesseraud, Sophie; Collin, Anne

    2014-01-01

    Fast-growing chickens have a limited ability to tolerate high temperatures. Thermal manipulation during embryogenesis (TM) has previously been shown to lower chicken body temperature (Tb) at hatching and to improve thermotolerance until market age, possibly resulting from changes in metabolic regulation. The aim of this study was to evaluate the long-term effects of TM (12 h/d, 39.5°C, 65% RH from d 7 to 16 of embryogenesis vs. 37.8°C, 56% RH continuously) and of a subsequent heat challenge (32°C for 5 h at 34 d) on the mRNA expression of metabolic genes and cell signaling in the Pectoralis major muscle and the liver. Gene expression was analyzed by RT-qPCR in 8 chickens per treatment, characterized by low Tb in the TM groups and high Tb in the control groups. Data were analyzed using the general linear model of SAS considering TM and heat challenge within TM as main effects. TM had significant long-term effects on thyroid hormone metabolism by decreasing the muscle mRNA expression of deiodinase DIO3. Under standard rearing conditions, the expression of several genes involved in the regulation of energy metabolism, such as transcription factor PGC-1α, was affected by TM in the muscle, whereas for other genes regulating mitochondrial function and muscle growth, TM seemed to mitigate the decrease induced by the heat challenge. TM increased DIO2 mRNA expression in the liver (only at 21°C) and reduced the citrate synthase activity involved in the Krebs cycle. The phosphorylation level of p38 Mitogen-activated-protein kinase regulating the cell stress response was higher in the muscle of TM groups compared to controls. In conclusion, markers of energy utilization and growth were either changed by TM in the Pectoralis major muscle and the liver by thermal manipulation during incubation as a possible long-term adaptation limiting energy metabolism, or mitigated during heat challenge. PMID:25180913

  20. Differential Muscle Involvement in Mice and Humans Affected by McArdle Disease.

    PubMed

    Krag, Thomas O; Pinós, Tomàs; Nielsen, Tue L; Brull, Astrid; Andreu, Antoni L; Vissing, John

    2016-05-01

    McArdle disease (muscle glycogenosis type V) is caused by myophosphorylase deficiency, which leads to impaired glycogen breakdown. We investigated how myophosphorylase deficiency affects muscle physiology, morphology, and glucose metabolism in 20-week-old McArdle mice and compared the findings to those in McArdle disease patients. Muscle contractions in the McArdle mice were affected by structural degeneration due to glycogen accumulation, and glycolytic muscles fatigued prematurely, as occurs in the muscles of McArdle disease patients. Homozygous McArdle mice showed muscle fiber disarray, variations in fiber size, vacuoles, and some internal nuclei associated with cytosolic glycogen accumulation and ongoing regeneration; structural damage was seen only in a minority of human patients. Neither liver nor brain isoforms of glycogen phosphorylase were upregulated in muscles, thus providing no substitution for the missing muscle isoform. In the mice, the tibialis anterior (TA) muscles were invariably more damaged than the quadriceps muscles. This may relate to a 7-fold higher level of myophosphorylase in TA compared to quadriceps in wild-type mice and suggests higher glucose turnover in the TA. Thus, despite differences, the mouse model of McArdle disease shares fundamental physiological and clinical features with the human disease and could be used for studies of pathogenesis and development of therapies. PMID:27030740

  1. Organochlorines including polychlorinated biphenyls in muscle, liver, and ovaries of cod, Gadus morhua

    SciTech Connect

    Hellou, J.; Warren, W.G.; Payne, J.F. )

    1993-11-01

    Twenty-three specific organochlorine contaminants and polychlorinated biphenyls (PCBs), measured as three Aroclor standards were analyzed in muscle, liver, and ovaries of cod, Gadus morhua, collected in the Northwest Atlantic. In general, contaminants were undetectable in muscle tissue, while concentrations were 10 times lower in ovaries than liver (wet weight). Comparison of results to other locations indicated a similarity between the ratio of the concentrations of p,p'-DDE, p,p'-DDD and p,p'-DDT, in liver of cod from the northern North Sea and from the Northwest Atlantic, although with lower levels in the present study. The ratio of alpha-HCH and gamma-HCH was between that of the central and northern North Sea. Similar ratios tend to indicate similar residence times in the atmosphere, from source to sampling area. Comparison of sigma PCB and sigma DDT in the liver of cod from various geographical locations showed the following general trend in concentrations: Arctic, Northwest Atlantic, West Atlantic, Norway < North Baltic, Nova Scotia, North Sea < South Baltic. It was observed that if the liver concentration of one compound was low (high), there was a tendency for all compounds to be low (high). Cluster analysis of organochlorines in liver pointed to the presence of four basic clusters, which could reflect similar physical chemical properties within a group. Concentrations of organochlorines in ovaries were below levels expected to affect egg and larval viability.

  2. Skeletal muscle insulin resistance in hamsters with diabetes developed from obesity is involved in abnormal skeletal muscle LXR, PPAR and SREBP expression

    PubMed Central

    LI, GUO-SHENG; LIU, XU-HAN; ZHU, HUA; HUANG, LAN; LIU, YA-LI; MA, CHUN-MEI

    2016-01-01

    Diabetic ‘lipotoxicity’ theory suggests that fat-induced skeletal muscle insulin resistance (FISMIR) in obesity induced by a high-fat diet (HFD), which leads to ectopic lipid accumulation in insulin-sensitive tissues, may play a pivotal role in the pathogenesis of type 2 diabetes. However, the changes in gene expression and the molecular mechanisms associated with the pathogenesis of FISMIR have not yet been fully elucidated. In the present study the changes in skeletal muscle gene expression were examined in FISMIR in obese insulin-resistant and diabetic hamster models induced by HFD with or without low-dose streptozotocin-treatment. Microarray technology and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to explore the potential underlying molecular mechanisms. The pathophysiological and metabolic features of obesity and type 2 diabetes in humans are closely resembled by these hamster models. The results of microarray analysis showed that the differentially expressed genes associated with metabolism were mostly related to the abnormal regulation and changes in the gene expression of liver X receptor (LXR), peroxisome proliferator-activated receptor (PPAR) and sterol regulatory element-binding protein (SREBP) transcriptional programs in the skeletal muscle from insulin-resistant and diabetic hamsters. The microarray findings confirmed by RT-qPCR indicated that the increased expression of SREBPs and LXRβ and the decreased expression of LXRα and PPARs were involved in the molecular mechanisms of FISMIR pathogenesis in insulin-resistant and diabetic hamsters. A significant difference in the abnormal expression of skeletal muscle LXRs, PPARs and SREBPs was found between insulin-resistant and diabetic hamsters. It may be concluded that the combined abnormal expression of LXR, PPAR and SREBP transcriptional programs may contribute to the development of FISMIR mediated by skeletal muscle lipid accumulation resulting from abnormal

  3. A Case Report of the Angiosarcoma Involving Epicranial Muscle and Fascia : Is the Occipitofrontalis Muscle Composed of Two Different Muscles?

    PubMed Central

    Kim, Ho Kyun

    2016-01-01

    The occipitofrontalis muscle is generally regarded as one muscle composed of two muscle bellies joined through the galea aponeurotica. However, two muscle bellies have different embryological origin, anatomical function and innervations. We report a case of angiosarcoma of the scalp in a 63-year-old man whose MR showed that the superficial fascia overlying the occipital belly becomes the temporoparietal fascia and ends at the superior end of the frontal belly. Beneath the superficial fascia, the occipital belly of the occipitofrontalis muscle becomes the galea aponeurotica and inserts into the underside of the frontal belly. The presented case report supported the concept of which the occipitofrontalis muscle appears to be composed of two anatomically different muscles. PMID:26885292

  4. Mitochondrial involvement in drug-induced liver injury.

    PubMed

    Pessayre, Dominique; Mansouri, Abdellah; Berson, Alain; Fromenty, Bernard

    2010-01-01

    Mitochondrial dysfunction is a major mechanism of liver injury. A parent drug or its reactive metabolite can trigger outer mitochondrial membrane permeabilization or rupture due to mitochondrial permeability transition. The latter can severely deplete ATP and cause liver cell necrosis, or it can instead lead to apoptosis by releasing cytochrome c, which activates caspases in the cytosol. Necrosis and apoptosis can trigger cytolytic hepatitis resulting in lethal fulminant hepatitis in some patients. Other drugs severely inhibit mitochondrial function and trigger extensive microvesicular steatosis, hypoglycaemia, coma, and death. Milder and more prolonged forms of drug-induced mitochondrial dysfunction can also cause macrovacuolar steatosis. Although this is a benign liver lesion in the short-term, it can progress to steatohepatitis and then to cirrhosis. Patient susceptibility to drug-induced mitochondrial dysfunction and liver injury can sometimes be explained by genetic or acquired variations in drug metabolism and/or elimination that increase the concentration of the toxic species (parent drug or metabolite). Susceptibility may also be increased by the presence of another condition, which also impairs mitochondrial function, such as an inborn mitochondrial cytopathy, beta-oxidation defect, certain viral infections, pregnancy, or the obesity-associated metabolic syndrome. Liver injury due to mitochondrial dysfunction can have important consequences for pharmaceutical companies. It has led to the interruption of clinical trials, the recall of several drugs after marketing, or the introduction of severe black box warnings by drug agencies. Pharmaceutical companies should systematically investigate mitochondrial effects during lead selection or preclinical safety studies. PMID:20020267

  5. Butyltins in muscle and liver of fish collected from certain Asian and Oceanian countries.

    PubMed

    Kannan, K; Tanabe, S; Iwata, H; Tatsukawa, R

    1995-01-01

    Concentrations of butyltin residues were determined in muscle tissue of fish collected from local markets and sea food shops in India, Bangladesh, Thailand, Indonesia, Vietnam, Taiwan, Australia, Papua New Guinea and the Solomon Islands. Contamination levels were determined in the Asia-Pacific region and human exposure was estimated. Similarly, corresponding liver samples of fish muscle collected in Australia, Papua New Guinea and the Solomon Islands were analyzed to obtain information on partitioning of butyltin compounds between muscle and liver tissues. Butyltin compounds were detected in most of the samples which suggested widespread contamination in Asia and Oceania. The concentrations of butyltin compounds were, on average, an order of magnitude higher in liver than in muscle. Residue concentration of Sigmabutyltin in liver was found to be correlated significantly (p < 0.02) with those in muscle. Intensive ship-scrapping activities, sewage disposal and antifouling paints are considered the major sources of butyltins in this region. Increased proportions of MBT over DBT and TBT in samples from most locations indicated degradation of TBT to MBT in fish tissues during storage at 4 degrees C in the dark over 1-2 years. The possibility that fish have been subject to increased exposure to MBT and that TBT degrades to MBT quite rapidly in tropical environments are also considered. Butyltin concentrations in fish from Asia and Oceania were lower than those reported for Japan, Canada and the USA. Although the number of samples analyzed from each country was small, it is tentatively suggested that intake of butyltins by humans via consumption of fish in these countries was < 25% of the tolerable daily intake of 250 ng kg bw(-1) day(-1). To our knowledge, this is the first study reporting on butyltin pollution in developing Asian countries. PMID:15091461

  6. Sensitivity of fructose-1,6-biphosphatase from yeast, liver and skeletal muscle to fructose-2,6-biphosphate and 5'-adenosine monophosphate.

    PubMed

    von Herrath, M; Holzer, H

    1988-05-01

    As a prerequisite for future studies on the possible effect of sulphite, an anti-microbial agent, on gluconeogenesis in yeast, a comparative study of fructose-1,6-bisphosphatase (FBPase), a key enzyme of gluconeogenesis, from yeast, liver and skeletal muscle is reported. In contrast to FBPase from yeast or liver, FBPase from skeletal muscle is approximately 1000-fold more sensitive to inhibition by 5' adenosine monophosphate and 30 to 250-fold less sensitive to inhibition by fructose-2,6-bisphosphate. The kinetic properties of the FBPases, determined by the ratios R(Mg2+/Mn2+) and R (pH 7/9) of the enzyme activities, measured at 10 mM Mg2+ and 2 mM Mn2+ and at pH 7.0 and 9.0, respectively, show a drastic difference between the skeletal muscle and the yeast or liver enzymes. The data support the idea that the enzymes from yeast and liver function in gluconeogenesis, whereas the enzyme from skeletal muscle is involved in other biological functions. PMID:3291467

  7. Patterns of arm muscle activation involved in octopus reaching movements.

    PubMed

    Gutfreund, Y; Flash, T; Fiorito, G; Hochner, B

    1998-08-01

    The extreme flexibility of the octopus arm allows it to perform many different movements, yet octopuses reach toward a target in a stereotyped manner using a basic invariant motor structure: a bend traveling from the base of the arm toward the tip (Gutfreund et al., 1996a). To study the neuronal control of these movements, arm muscle activation [electromyogram (EMG)] was measured together with the kinematics of reaching movements. The traveling bend is associated with a propagating wave of muscle activation, with maximal muscle activation slightly preceding the traveling bend. Tonic activation was occasionally maintained afterward. Correlation of the EMG signals with the kinematic variables (velocities and accelerations) reveals that a significant part of the kinematic variability can be explained by the level of muscle activation. Furthermore, the EMG level measured during the initial stages of movement predicts the peak velocity attained toward the end of the reaching movement. These results suggest that feed-forward motor commands play an important role in the control of movement velocity and that simple adjustment of the excitation levels at the initial stages of the movement can set the velocity profile of the whole movement. A simple model of octopus arm extension is proposed in which the driving force is set initially and is then decreased in proportion to arm diameter at the bend. The model qualitatively reproduces the typical velocity profiles of octopus reaching movements, suggesting a simple control mechanism for bend propagation in the octopus arm. PMID:9671683

  8. Metabolic Response to Heat Stress in Late-Pregnant and Early Lactation Dairy Cows: Implications to Liver-Muscle Crosstalk

    PubMed Central

    Eslamizad, Mehdi; Weitzel, Joachim; Kuhla, Björn

    2016-01-01

    Climate changes lead to rising temperatures during summer periods and dramatic economic losses in dairy production. Modern high-yielding dairy cows experience severe metabolic stress during the transition period between late gestation and early lactation to meet the high energy and nutrient requirements of the fetus or the mammary gland, and additional thermal stress during this time has adverse implications on metabolism and welfare. The mechanisms enabling metabolic adaptation to heat apart from the decline in feed intake and milk yield are not fully elucidated yet. To distinguish between feed intake and heat stress related effects, German Holstein dairy cows were first kept at thermoneutral conditions at 15°C followed by exposure to heat-stressed (HS) at 28°C or pair-feeding (PF) at 15°C for 6 days; in late-pregnancy and again in early lactation. Liver and muscle biopsies and plasma samples were taken to assess major metabolic pathway regulation using real-time PCR and Western Blot. The results indicate that during heat stress, late pregnant cows activate Cahill but reduce Cori cycling, prevent increase in skeletal muscle fatty acid oxidation, and utilize increased amounts of pyruvate for gluconeogenesis, without altering ureagenesis despite reduced plane of nutrition. These homeorhetic adaptations are employed to reduce endogenous heat production while diverting amino acids to the growing fetus. Metabolic adaptation to heat stress in early lactation involves increased long-chain fatty acid degradation in muscle peroxisomes, allowance for muscle glucose utilization but diminished hepatic use of amino acid-derived pyruvate for gluconeogenesis and reduced peroxisomal fatty acid oxidation and ATP production in liver of HS compared to PF cows in early lactation. Consequently, metabolic adaptation to heat stress and reduced feed intake differ between late pregnancy and early lactation of dairy cows to maintain energy supply for fetus development or milk production

  9. Metabolic Response to Heat Stress in Late-Pregnant and Early Lactation Dairy Cows: Implications to Liver-Muscle Crosstalk.

    PubMed

    Koch, Franziska; Lamp, Ole; Eslamizad, Mehdi; Weitzel, Joachim; Kuhla, Björn

    2016-01-01

    Climate changes lead to rising temperatures during summer periods and dramatic economic losses in dairy production. Modern high-yielding dairy cows experience severe metabolic stress during the transition period between late gestation and early lactation to meet the high energy and nutrient requirements of the fetus or the mammary gland, and additional thermal stress during this time has adverse implications on metabolism and welfare. The mechanisms enabling metabolic adaptation to heat apart from the decline in feed intake and milk yield are not fully elucidated yet. To distinguish between feed intake and heat stress related effects, German Holstein dairy cows were first kept at thermoneutral conditions at 15°C followed by exposure to heat-stressed (HS) at 28°C or pair-feeding (PF) at 15°C for 6 days; in late-pregnancy and again in early lactation. Liver and muscle biopsies and plasma samples were taken to assess major metabolic pathway regulation using real-time PCR and Western Blot. The results indicate that during heat stress, late pregnant cows activate Cahill but reduce Cori cycling, prevent increase in skeletal muscle fatty acid oxidation, and utilize increased amounts of pyruvate for gluconeogenesis, without altering ureagenesis despite reduced plane of nutrition. These homeorhetic adaptations are employed to reduce endogenous heat production while diverting amino acids to the growing fetus. Metabolic adaptation to heat stress in early lactation involves increased long-chain fatty acid degradation in muscle peroxisomes, allowance for muscle glucose utilization but diminished hepatic use of amino acid-derived pyruvate for gluconeogenesis and reduced peroxisomal fatty acid oxidation and ATP production in liver of HS compared to PF cows in early lactation. Consequently, metabolic adaptation to heat stress and reduced feed intake differ between late pregnancy and early lactation of dairy cows to maintain energy supply for fetus development or milk production

  10. Atrazine exposure causes mitochondrial toxicity in liver and muscle cell lines

    PubMed Central

    Sagarkar, Sneha; Gandhi, Deepa; Devi, S. Saravana; Sakharkar, Amul; Kapley, Atya

    2016-01-01

    Objective: Chronic exposure to atrazine and other pesticides is reported to cause metabolic disorders, yet information on effects of atrazine on expression of genes relevant to mitochondrial function is largely missing. In the present study, therefore, we investigated the expression of a battery of nuclear- and mitochondrial-encoded genes involved in oxidative phosphorylation (OXPHOS) in human liver (HepG2) and rat muscle (L6) cell lines due to short-term atrazine exposure. Materials and Methods: We have determined the EC50 values of atrazine for cytotoxicity and mitochondrial toxicity (mitotoxicity) in terms of adenosine triphosphate (ATP) content in HepG2 and L6 cells. Further, the mRNA expression of nuclear- and mitochondrial-encoded genes was analyzed using quantitative real-time polymerase chain reaction. Results: The EC50 value of atrazine for mitotoxicity in HepG2 and L6 cells was found to be about 0.162 and 0.089 mM, respectively. Mitochondrial toxicity was indicated by reduction in ATP content following atrazine exposure. Atrazine exposure resulted in down-regulation of many OXPHOS subunits expression and affected biogenesis factors’ expression. Most prominently, superoxide dismutase (SOD) and sirtuin 3 (SIRT3) expressions were up-regulated in HepG2 cells, whereas SIRT3 expression was alleviated in L6 cells, without significant changes in SOD levels. Mitochondrial transcription factor A (TFAM) and SIRT1 expression were significantly down-regulated in both cell lines. Conclusion: Results suggest that TFAM and SIRT1 could be involved in atrazine-induced mitochondrial dysfunction, and further studies can be taken up to understand the mechanism of mitochondrial toxicity. Further study can also be taken up to explore the possibility of target genes as biomarkers of pesticide toxicity. PMID:27114639

  11. [Preferential distal muscle involvement in case of oculopharyngeal muscular dystrophy with (GCG) 13 expansion].

    PubMed

    Nakashima, Dainari; Nakajima, Hideto; Ishida, Shimon; Sugino, Masakazu; Kimura, Fumiharu; Hanafusa, Toshiaki

    2003-09-01

    We reported a 52-year-old woman with oculopharyngeal muscular dystrophy (OPMD) harboring expanded (GCG) 13 mutation of the poly (A) binding protein 2 gene. She presented not only ptosis and dysphagia but distal dominant muscle atrophy in four extremities. CT demonstrated distal muscle atrophy with marked fat replacement in the biceps femoris, semitendinosus, membraneous, soleus, and gastrocnemius muscles. Although OPMD is considered to be a muscle disease, this patient showed even neurogenic features in the electrophysiological and pathological findings. Although previous reports indicate that OPMD is genetically homogeneous disease, some cases with OPMD may show some atypical features associated with neurogenic involvement. PMID:14727564

  12. Substrate repletion in rat myocardium, liver, and skeletal muscles after exercise.

    PubMed

    Poland, J L; Trowbridge, C; Poland, J W

    1980-10-01

    Carbohydrate and lipid substrates were measured in rats during recovery following exercise or a 24-h fast and compared with values from time-matched control (rested, fed) rats. After exercise muscle glycogen recovered at the expense of liver glycogen repletion. Myocardial glycogen supercompensated whereas soleus, red vastus lateralis (RVL) and white vastus lateralis glycogen merely returned to control levels. A similar recovery pattern occurred after fasting with refeeding promoting glycogen synthesis in the liver, skeletal muscles, and even in the myocardium, where glycogen had already been elevated by the fast. Both soleus and RVL muscles, along with the myocardium, exhibited glycogen supercompensation. Both exercise and fasting increased plasma free fatty acid (FFA) levels which favor myocardial glycogen synthesis. Unchanged tissue triglycerides and relatively stable blood glucose levels suggest that these are unlikely influences on glycogen recovery. It is concluded that exercise per se is unlikely to induce glycogen supercompensation in skeletal muscles though myocardial glycogen supercompensation readily occurs, that food restriction prior to exercise quantitatively affects substrate recovery though its impact could go unnoticed because of the qualitative similarities between substrate recovery following exercise or fasting, and that FFA is the only major energy substrate concurrently changing with glycogen after exercise or fasting which could facilitate glycogen synthesis. PMID:7470995

  13. Prelamin A is involved in early steps of muscle differentiation

    SciTech Connect

    Capanni, Cristina; Del Coco, Rosalba; Squarzoni, Stefano; Columbaro, Marta; Mattioli, Elisabetta; Rocchi, Anna; Scotlandi, Katia; Maraldi, Nadir; Foisner, Roland; Lattanzi, Giovanna

    2008-12-10

    Lamin A is a nuclear lamina constituent implicated in a number of human disorders including Emery-Dreifuss muscular dystrophy. Since increasing evidence suggests a role of the lamin A precursor in nuclear functions, we investigated the processing of prelamin A during differentiation of C2C12 mouse myoblasts. We show that both protein levels and cellular localization of prelamin A are modulated during myoblast activation. Similar changes of lamin A-binding proteins emerin and LAP2{alpha} were observed. Furthermore, prelamin A was found in a complex with LAP2{alpha} in differentiating myoblasts. Prelamin A accumulation in cycling myoblasts by expressing unprocessable mutants affected LAP2{alpha} and PCNA amount and increased caveolin 3 mRNA and protein levels, while accumulation of prelamin A in differentiated muscle cells following treatment with a farnesyl transferase inhibitor appeared to inhibit caveolin 3 expression. Our data provide evidence for a critical role of the lamin A precursor in the early steps of muscle cell differentiation.

  14. Dopamine receptors in the substantia nigra are involved in the regulation of muscle tone.

    PubMed Central

    Double, K L; Crocker, A D

    1995-01-01

    The aim of the present study was to localize the dopamine receptors involved in the regulation of muscle tone. A strategy was used whereby the effects on muscle tone of injecting the irreversible dopamine receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) in discrete brain regions were assessed. Increases in muscle tone were measured as changes in electromyographic activity of the gastrocnemius and tibialis muscles of conscious, unrestrained rats. No increases in muscle tone were found after injections of EEDQ into the anterior and posterior striatum, which produced marked reductions in dopamine receptor concentration. The effects of muscle tone of injecting EEDQ into the substantia nigra pars reticulata were also assessed. Large increases in muscle tone were observed associated with inactivation of either D1 or D2 dopamine receptors in the substantia nigra. The increased muscle tone was not reduced by subcutaneous administration of apomorphine, despite the presence of a normal population of striatal dopamine receptors. These findings provide evidence that dopamine receptors in the substantia nigra play an important role in the regulation of muscle tone. Further, they challenge the hypothesis that the muscle rigidity of Parkinson disease results primarily from loss of striatal dopamine receptor stimulation. Images Fig. 1 Fig. 3 PMID:7878037

  15. Dietary (-)-Epigallocatechin-3-gallate Supplementation Counteracts Aging-Associated Skeletal Muscle Insulin Resistance and Fatty Liver in Senescence-Accelerated Mouse.

    PubMed

    Liu, Hung-Wen; Chan, Yin-Ching; Wang, Ming-Fu; Wei, Chu-Chun; Chang, Sue-Joan

    2015-09-30

    Aging is accompanied by pathophysiological changes including insulin resistance and fatty liver. Dietary supplementation with (-)-epigallocatechin-3-gallate (EGCG) improves insulin sensitivity and attenuates fatty liver disease. We hypothesized that EGCG could effectively modulate aging-associated changes in glucose and lipid metabolism in senescence-accelerated mice (SAM) prone 8 (SAMP8). Higher levels of glucose, insulin, and free fatty acid, inhibited Akt activity, and decreased glucose transporter 4 (GLUT4) expression were observed in SAMP8 mice compared to the normal aging group, SAM resistant 1 mice. EGCG supplementation for 12 weeks successfully decreased blood glucose and insulin levels via restoring Akt activity and GLUT4 expression and stimulating AMPKα activation in skeletal muscle. EGCG up-regulated genes involved in mitochondrial biogenesis and subsequently restored mitochondrial DNA copy number in skeletal muscle of SAMP8 mice. Decreased adipose triglyceride lipase and increased sterol regulatory element binding proteins-1c (SREBP-1c) and carbohydrate responsive element binding protein at mRNA levels were observed in SAMP8 mice in accordance with hepatocellular ballooning and excess lipid accumulation. The pevention of hepatic lipid accumulation by EGCG was mainly attributed to down-regulation of mTOR and SREBP-1c-mediated lipid biosynthesis via suppression of the positive regulator, Akt, and activation of the negative regulator, AMPKα, in the liver. EGCG beneficially modulates glucose and lipid homeostasis in skeletal muscle and liver, leading to alleviation of aging-associated metabolic disorders. PMID:26152236

  16. CT and MRI of diffuse lobar involvement pattern in liver pathology.

    PubMed

    Karçaaltincaba, Muşturay; Sirlin, Claude B

    2011-12-01

    Focal, segmental, and diffuse liver pathologies have been described in the literature. This article describes a pattern in which liver pathology is confined to a lobe. This lobar pattern has not been described previously to our knowledge. Herein, we illustrate computed tomography (CT) and magnetic resonance imaging (MRI) findings of diffuse lobar involvement patterns in various liver conditions. Diffuse lobar involvement can be observed in benign (steatosis, hepatic iron overload, cholestasis, perfusion alterations, infarction, alveolar hydatid cysts, trauma, and hemangiomas) and primary malignant (hepatocellular carcinoma) pathologies. Diffuse lobar involvement in metastatic disease appears to be rare. Due in part to their potentially unusual appearances, the diagnosis of lobar pathologies using imaging can be challenging, and entities with lobar patterns can cause diagnostic confusion. Liver MRI can be used as a problem-solving tool for diffuse lobar pathologies detected on ultrasonography and CT. Inand out-of-phase MRI can help in the assessment of lobar fat accumulation. PMID:21053176

  17. 18F-FDG PET/CT Imaging of Burkitt Lymphoma Presenting With Unusual Muscle Involvement.

    PubMed

    Dirlik Serim, Burcu; Gurleyen Eren, Tuba; Oz Puyan, Fulya; Durmus Altun, Gülay

    2016-08-01

    Extranodal involvement is more common with Burkitt lymphoma (BL) than other subtypes of non-Hodgkin lymphoma in childhood. According to our knowledge, there are rare cases in the literature about muscle involvement of BL, and its F-FDG PET/CT findings were not well defined. We report a 6-year-old girl with a histopathologic diagnosis of BL and referred for staging with PET/CT. FDG-avid abdominal lymph nodes and diffuse involvements of right quadriceps muscle were demonstrated. PMID:27124681

  18. Muscle and liver-specific alterations in lipid and acylcarnitine metabolism after a single bout of exercise in mice

    PubMed Central

    Hoene, Miriam; Li, Jia; Li, Yanjie; Runge, Heike; Zhao, Xinjie; Häring, Hans-Ulrich; Lehmann, Rainer; Xu, Guowang; Weigert, Cora

    2016-01-01

    Intracellular lipid pools are highly dynamic and tissue-specific. Physical exercise is a strong physiologic modulator of lipid metabolism, but most studies focus on changes induced by long-term training. To assess the acute effects of endurance exercise, mice were subjected to one hour of treadmill running, and 13C16-palmitate was applied to trace fatty acid incorporation in soleus and gastrocnemius muscle and liver. The amounts of carnitine, FFA, lysophospholipids and diacylglycerol and the post-exercise increase in acetylcarnitine were pronouncedly higher in soleus than in gastrocnemius. In the liver, exercise increased the content of lysophospholipids, plasmalogens and carnitine as well as transcript levels of the carnitine transporter. 13C16-palmitate was detectable in several lipid and acylcarnitine species, with pronounced levels of tracer-derived palmitoylcarnitine in both muscles and a strikingly high incorporation into triacylglycerol and phosphatidylcholine in the liver. These data illustrate the high lipid storing activity of the liver immediately after exercise whereas in muscle, fatty acids are directed towards oxidation. The observed muscle-specific differences accentuate the need for single-muscle analyses as well as careful consideration of the particular muscle employed when studying lipid metabolism in mice. In addition, our results reveal that lysophospholipids and plasmalogens, potential lipid signalling molecules, are acutely regulated by physical exercise. PMID:26916151

  19. Muscle and liver-specific alterations in lipid and acylcarnitine metabolism after a single bout of exercise in mice.

    PubMed

    Hoene, Miriam; Li, Jia; Li, Yanjie; Runge, Heike; Zhao, Xinjie; Häring, Hans-Ulrich; Lehmann, Rainer; Xu, Guowang; Weigert, Cora

    2016-01-01

    Intracellular lipid pools are highly dynamic and tissue-specific. Physical exercise is a strong physiologic modulator of lipid metabolism, but most studies focus on changes induced by long-term training. To assess the acute effects of endurance exercise, mice were subjected to one hour of treadmill running, and (13)C16-palmitate was applied to trace fatty acid incorporation in soleus and gastrocnemius muscle and liver. The amounts of carnitine, FFA, lysophospholipids and diacylglycerol and the post-exercise increase in acetylcarnitine were pronouncedly higher in soleus than in gastrocnemius. In the liver, exercise increased the content of lysophospholipids, plasmalogens and carnitine as well as transcript levels of the carnitine transporter. (13)C16-palmitate was detectable in several lipid and acylcarnitine species, with pronounced levels of tracer-derived palmitoylcarnitine in both muscles and a strikingly high incorporation into triacylglycerol and phosphatidylcholine in the liver. These data illustrate the high lipid storing activity of the liver immediately after exercise whereas in muscle, fatty acids are directed towards oxidation. The observed muscle-specific differences accentuate the need for single-muscle analyses as well as careful consideration of the particular muscle employed when studying lipid metabolism in mice. In addition, our results reveal that lysophospholipids and plasmalogens, potential lipid signalling molecules, are acutely regulated by physical exercise. PMID:26916151

  20. Effect of exercise training on the fatty acid composition of lipid classes in rat liver, skeletal muscle, and adipose tissue.

    PubMed

    Petridou, Anatoli; Nikolaidis, Michalis G; Matsakas, Antonis; Schulz, Thorsten; Michna, Horst; Mougios, Vassilis

    2005-05-01

    The aim of the present study was to examine the effects of 8 weeks of exercise training on the fatty acid composition of phospholipids (PL) and triacylglycerols (TG) in rat liver, skeletal muscle (gastrocnemius medialis), and adipose tissue (epididymal and subcutaneous fat). For this purpose, the relevant tissues of 11 trained rats were compared to those of 14 untrained ones. Training caused several significant differences of large effect size in the concentrations and percentages of individual fatty acids in the aforementioned lipid classes. The fatty acid composition of liver PL, in terms of both concentrations and percentages, changed with training. The TG content of muscle and subcutaneous adipose tissue decreased significantly with training. In contrast to the liver, where no significant differences in the fatty acid profile of TG were found, muscle underwent more significant differences in TG than PL, and adipose tissue only in TG. Most differences were in the same direction in muscle and adipose tissue TG, suggesting a common underlying mechanism. Estimated fatty acid elongase activity was significantly higher, whereas Delta(9)-desaturase activity was significantly lower in muscle and adipose tissue of the trained rats. In conclusion, exercise training modified the fatty acid composition of liver PL, muscle PL and TG, as well as adipose tissue TG. These findings may aid in delineating the effects of exercise on biological functions such as membrane properties, cell signaling, and gene expression. PMID:15682327

  1. [Perioperative management for liver transplant in a patient with familial amyloid polyneuropathy with heart involvement].

    PubMed

    López-Herrera Rodríguez, D; Guerrero Domínguez, R; Mellado Miras, P; Gómez Sosa, L

    2015-01-01

    Familial amyloid polyneuropathy (FAP) is a systemic amyloidosis caused by mutated transthyretin. Cardiac amyloidosis, the major prognostic determinant in systemic amyloidosis, is characterized by infiltration of the myocardium, leading to cardiomyopathy and conduction disturbances. Liver transplantation is the only curative option for patients with FAP. The case is presented of a 36-year-old patient with type i FAP with cardiac involvement, proposed for liver transplant surgery, which was successfully performed without any preoperative event of interest. PMID:24742789

  2. Unraveling the Molecular Signatures of Oxidative Phosphorylation to Cope with the Nutritionally Changing Metabolic Capabilities of Liver and Muscle Tissues in Farmed Fish

    PubMed Central

    Bermejo-Nogales, Azucena; Calduch-Giner, Josep Alvar; Pérez-Sánchez, Jaume

    2015-01-01

    Mitochondrial oxidative phosphorylation provides over 90% of the energy produced by aerobic organisms, therefore the regulation of mitochondrial activity is a major issue for coping with the changing environment and energy needs. In fish, there is a large body of evidence of adaptive changes in enzymatic activities of the OXPHOS pathway, but less is known at the transcriptional level and the first aim of the present study was to define the molecular identity of the actively transcribed subunits of the mitochondrial respiratory chain of a livestock animal, using gilthead sea bream as a model of farmed fish with a high added value for European aquaculture. Extensive BLAST searches in our transcriptomic database (www.nutrigroup-iats.org/seabreamdb) yielded 97 new sequences with a high coverage of catalytic, regulatory and assembly factors of Complex I to V. This was the basis for the development of a PCR array for the simultaneous profiling of 88 selected genes. This new genomic resource allowed the differential gene expression of liver and muscle tissues in a model of 10 fasting days. A consistent down-regulated response involving 72 genes was made by the liver, whereas an up-regulated response with 29 and 10 differentially expressed genes was found in white skeletal muscle and heart, respectively. This differential regulation was mostly mediated by nuclear-encoded genes (skeletal muscle) or both mitochondrial- and nuclear-encoded genes (liver, heart), which is indicative of a complex and differential regulation of mitochondrial and nuclear genomes, according to the changes in the lipogenic activity of liver and the oxidative capacity of glycolytic and highly oxidative muscle tissues. These insights contribute to the identification of the most responsive elements of OXPHOS in each tissue, which is of relevance for the appropriate gene targeting of nutritional and/or environmental metabolic disturbances in livestock animals. PMID:25875231

  3. Skeletal muscle IL-6 and regulation of liver metabolism during high-fat diet and exercise training.

    PubMed

    Knudsen, Jakob G; Joensen, Ella; Bertholdt, Lærke; Jessen, Henrik; van Hauen, Line; Hidalgo, Juan; Pilegaard, Henriette

    2016-05-01

    Interleukin (IL)-6 is released from skeletal muscle (SkM) during exercise and has been shown to affect hepatic metabolism. It is, however, unknown whether SkM IL-6 is involved in the regulation of exercise training-induced counteraction of changes in carbohydrate and lipid metabolism in the liver in response to high-fat diet (HFD) feeding. Male SkM-specific IL-6 KO (MKO) and Floxed mice were subjected to Chow diet, HFD or HFD combined with exercise training (HFD ExTr) for 16 weeks. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) protein content decreased with both HFD and HFD ExTr in Floxed mice, but increased in IL-6 MKO mice on HFD In addition, the intrahepatic glucose concentration was in IL-6 MKO mice higher in HFD than chow. Within HFD ExTr mice, hepatic glucose-6-phosphatase (G6Pase) 36 kDa protein content was higher in IL-6 MKO than Floxed mice. Hepatic pyruvate dehydrogenase kinase (PDK) 4 and PDK2 protein content was in Floxed mice lower in HFD ExTr than Chow. In addition, hepatic ACC1-phosphorylation was higher and ACC1 protein lower in HFD Together this suggests that SkM IL-6 regulates hepatic glucose metabolism, but does not seem to be of major importance for the regulation of oxidative capacity or lipogenesis in liver during HFD or HFD combined with exercise training. PMID:27185906

  4. The lead, cadmium and mercury concentrations in muscle, liver and kidney from Finnish pigs and cattle during 1987-1988.

    PubMed

    Niemi, A; Venäläinen, E R; Hirvi, T; Hirn, J; Karppanen, E

    1991-05-01

    The lead, cadmium and mercury concentrations in muscle, liver and kidney from Finnish pigs and cattle were determined. The average wet weight lead concentrations in pig muscle, liver and kidney were 15 micrograms/kg, 38 micrograms/kg and 40 micrograms/kg, respectively. The corresponding concentrations for cattle were 13 micrograms/kg, 57 micrograms/kg and 110 micrograms/kg. The average wet weight cadmium concentrations were 1.5 micrograms/kg, 28 micrograms/kg and 170 micrograms/kg (pigs) and 1.3 micrograms/kg, 61 micrograms/kg and 350 micrograms/kg (cattle). The corresponding mercury concentrations were 11 micrograms/kg, 12 micrograms/kg and 14 micrograms/kg (pigs) and 11 micrograms/kg, 12 micrograms/kg and 15 micrograms/kg (cattle). The average concentrations were at or above the detection limit of the metal in question. According to the results obtained by the National Veterinary Institute, the cadmium concentration in pigs and cattle has decreased during the period 1973-1988. The provisional tolerable daily intake of lead/person (60 kg), recommended by GEMS/Food, is 0.43 mg. According to the results for lead levels in these products in Finland, a daily intake of 29 kg pig muscle, 33 kg cattle muscle, 11 kg pig liver, 8 kg cattle liver, 11 kg pig kidney or 4 kg cattle kidney would be required to reach this norm. The corresponding provisional tolerable daily intake of cadmium/person (60 kg) is 0.06 mg and is equivalent to 40 kg pig muscle, 46 kg cattle muscle, 2 kg pig liver, 1 kg cattle liver, 0.4 kg pig kidney and 0.2 kg cattle kidney. The validity of the methods was tested four times a year using spiked check samples. PMID:2058312

  5. Dose-response involvement of constitutive androstane receptor in mouse liver hypertrophy induced by triazole fungicides.

    PubMed

    Tamura, Kei; Inoue, Kaoru; Takahashi, Miwa; Matsuo, Saori; Irie, Kaoru; Kodama, Yukio; Ozawa, Shogo; Nishikawa, Akiyoshi; Yoshida, Midori

    2013-07-31

    To clarify the dose-response relationship between constitutive androstane receptor (CAR) activity and induction of cytochrome P450 2B (CYP2B) expression and hypertrophy by triazole fungicides in mouse liver, three dose levels of cyproconazole (Cypro), tebuconazole (Teb), fluconazole (Flu), and phenobarbital (PB), a typical CYP2B inducer, were administrated in diet to male wild-type (WT) and CAR-knockout (CARKO) mice for one week. In WT mice, all compounds dose-dependently induced liver weight increases and hepatocellular hypertrophy accompanied by CYP2B expression. In CARKO mice, these effects were not induced by PB, while Cypro or Flu induced these effects only at the highest dose. Dose-dependent liver hypertrophy was detected in CARKO mice treated with Teb, but at the lowest dose the intensity was weakened compared to WT mice. The present results indicate that Cypro and Flu mainly induced CAR-mediated liver hypertrophy, while Teb slightly involved CAR. The involvement of CAR in triazole-induced liver hypertrophy was dose-responsive. In addition, all three triazoles have non-CAR-mediated liver hypertrophy pathways, indicating that the hypertrophy induced by these triazoles differs from that of PB. PMID:23721867

  6. Non-Hodgkin's Lymphoma of Multiple Skeletal Muscles Involvement Seen on FDG PET/CT Scans

    PubMed Central

    Dai, Yue; Sowjanya, Medapati; You, Jia; Xu, Kai

    2015-01-01

    Abstract As normal healthy skeletal muscle does not contain lymphoid tissue, extra nodal lymphoma involving multiple muscles is rare, as well. This study reports a case of non-Hodgkin's lymphoma (NHL) of multiple skeletal muscles involvement and a review of differential diagnosis of it. A 37-year-old female presented to our hospital after being diagnosed with NHL for 7 months. She had received six courses of cyclophosphamide hydroxydaunorubicin oncovin prednisolone etoposide (CHOPE) chemotherapy. Then she felt pain and noticed swelling on her left calf. The fluorodeoxyglucose (18FDG) positron emission tomography (PET)/computed tomography (CT) image showed abnormal focal FDG uptake in hypo-pharynx, which was the primary NHL and also in multiple groups of muscles in whole body. As the patient has history NHL, lymphoma of multiple muscle involvement was suspected. Finally, an ultrasound-guided tissue biopsy was performed on the left calf and histological examination yielded lymphomatous cells infiltration in the left gastrocnemius. Through this report, we emphasize that a multidisciplinary team approach with clinician, radiologist, and pathologist is essential for proper diagnosis, staging, and management of such rare lesions. PMID:25950693

  7. Metabolic priorities during starvation: enzyme sparing in liver and white muscle of Atlantic cod, Gadus morhua L.

    PubMed

    Guderley, Helga; Lapointe, Dominique; Bédard, Martin; Dutil, Jean-Denis

    2003-06-01

    Atlantic cod, Gadus morhua, respond to starvation first by mobilising hepatic lipids, then muscle and hepatic glycogen and finally muscle proteins. The dual role of proteins as functional elements and energetic reserves should lead to a temporal hierarchy of mobilisation where the nature of a function dictates its conservation during starvation. We examined (1) whether lysosomal and anti-oxidant enzymes in liver and white muscle are spared during prolonged starvation, (2) whether the responses of these enzymes in muscle vary longitudinally. Hepatic contents of lysosomal proteases decreased with starvation, whereas those of catalase (CAT) increased and lysosomal enzymes of carbohydrate metabolism and glutathione S-transferase (GST) did not change. In white muscle, starvation decreased the specific activity of lysosomal enzymes of carbohydrate degradation and doubled that of cathepsin D (CaD). The activity of anti-oxidant enzymes and acid phosphatase in muscle was unchanged with starvation. In white muscle neither lysosomal enzymes nor anti-oxidant enzymes varied significantly with sampling position. In cod muscle, antioxidant enzymes, CaD and acid phosphatase are spared during a period of starvation that decreases lysosomal enzymes of carbohydrate metabolism and decreases glycolytic enzyme activities. In cod liver, the anti-oxidant enzymes, CAT and GST, were also spared during starvation. PMID:12781835

  8. Content of total iron, copper and manganese in liver of animals during hypokinesia, muscle activity and process of recovery

    NASA Technical Reports Server (NTRS)

    Potapovich, G. M.; Taneyeva, G. V.; Uteshev, A. B.

    1980-01-01

    It is shown that the content of total iron, copper and manganese in the liver of animals is altered depending on the intensity and duration of their swimming. Hypodynamia for 7 days does not alter the concentration of iron, but sufficiently increases the content of copper and manganese. The barometric factor effectively influences the maintenance of constancy in the content of microelements accumulated in the liver after intensive muscle activity.

  9. MRI in DNM2-related centronuclear myopathy: evidence for highly selective muscle involvement.

    PubMed

    Schessl, Joachim; Medne, Livija; Hu, Ying; Zou, Yaqun; Brown, Mark J; Huse, Jason T; Torigian, Drew A; Jungbluth, Heinz; Goebel, Hans-Hilmar; Bönnemann, Carsten G

    2007-01-01

    Dynamin 2 has recently been recognized as a causative gene for the autosomal dominant form of centronuclear myopathy (dominant centronuclear myopathy). Here we report an affected father and daughter with dynamin 2 related AD CNM with predominantly distal onset of weakness. In addition to the diagnostic central location of myonuclei the muscle biopsy also showed core-like structures. Muscle MRI in the lower leg revealed prominent involvement of the soleus, but also of the gastrocnemius and the tibialis anterior whereas in the thigh there was a consistent pattern of selective involvement of adductor longus, semimembranosus, biceps femoris, rectus femoris, and vastus intermedius with relative sparing of vastus lateralis and medialis, sartorius, gracilis, and partly of the semitendinosus. These characteristic findings on muscle MRI confirm similar findings reported for CT imaging in dynamin 2 related dominant centronuclear myopathy and may help to differentiate this disorder from central core disease and other myopathies. PMID:17134899

  10. Involvement of MicroRNAs in the Regulation of Muscle Wasting during Catabolic Conditions*

    PubMed Central

    Soares, Ricardo José; Cagnin, Stefano; Chemello, Francesco; Silvestrin, Matteo; Musaro, Antonio; De Pitta, Cristiano; Lanfranchi, Gerolamo; Sandri, Marco

    2014-01-01

    Loss of muscle proteins and the consequent weakness has important clinical consequences in diseases such as cancer, diabetes, chronic heart failure, and in aging. In fact, excessive proteolysis causes cachexia, accelerates disease progression, and worsens life expectancy. Muscle atrophy involves a common pattern of transcriptional changes in a small subset of genes named atrophy-related genes or atrogenes. Whether microRNAs play a role in the atrophy program and muscle loss is debated. To understand the involvement of miRNAs in atrophy we performed miRNA expression profiling of mouse muscles under wasting conditions such as fasting, denervation, diabetes, and cancer cachexia. We found that the miRNA signature is peculiar of each catabolic condition. We then focused on denervation and we revealed that changes in transcripts and microRNAs expression did not occur simultaneously but were shifted. Indeed, whereas transcriptional control of the atrophy-related genes peaks at 3 days, changes of miRNA expression maximized at 7 days after denervation. Among the different miRNAs, microRNA-206 and -21 were the most induced in denervated muscles. We characterized their pattern of expression and defined their role in muscle homeostasis. Indeed, in vivo gain and loss of function experiments revealed that miRNA-206 and miRNA-21 were sufficient and required for atrophy program. In silico and in vivo approaches identified transcription factor YY1 and the translational initiator factor eIF4E3 as downstream targets of these miRNAs. Thus miRNAs are important for fine-tuning the atrophy program and their modulation can be a novel potential therapeutic approach to counteract muscle loss and weakness in catabolic conditions. PMID:24891504

  11. Organochlorine contaminants in the muscle, liver and brain of seabirds (Larus) from the coastal area of the Southern Baltic.

    PubMed

    Falkowska, Lucyna; Reindl, Andrzej R; Grajewska, Agnieszka; Lewandowska, Anita U

    2016-11-01

    The presence of persistent organic pollutants in the environment manifests itself most strongly in the marine trophic chain, where the highest link is comprised of seabirds. At the same time, seabirds are excellent indicators of contamination in their habitat. The present study concentrates on toxic substances: polychlorinated dibenzo-p-dioxin (PCDDs), polychlorinated dibenzofurans (PCDFs) and chlorinated organic pesticides (OCPs) accumulated in the livers, pectoral muscles and brains of dead gulls collected along the Polish coast of the Baltic Sea in the years 2010-12. The highest toxic equivalence was determined in the livers of Larus argentatus (TEQ(birds TEF)-28.3pgg(-1) ww) and Larus marinus (TEQ(birds TEF)-29.9pgg(-1) ww.). However, the toxic equivalence of muscles was lower and amounted to 3.9pgg(-1) ww. and 7.8pgg(-1) ww. respectively for the two species. The lowest toxic equivalence was found in the brains of birds, where only one, the most toxic, 2,3,7,8 TCDD congener was found (TEQ(birds TEF) 0.87pgg(-1) ww). The highest concentration of chloroorganic pesticides was determined in the brains of the birds (total OCP 167.8pgg(-1) ww.), lower concentrations were found in the livers (total OCP 92.1pgg(-1) ww.) and muscles (total OCP 43.1pgg(-1) ww.). With regard to pesticides, the highest proportion in the total OCP content was constituted by DDT and its isomers (liver 81%, muscles 77% and brain 55%). High concentrations of the studied pollutants in the livers of gulls found dead on the coast of the Southern Baltic could have been effected by levels of contamination in the birds' last meals, which resulted in a seven-fold increase of the liver's toxic equivalence and a two-fold increase in OCP concentration in relation to muscles. PMID:27414257

  12. Adeno-Associated Viral Vector-Mediated Transgene Expression Is Independent of DNA Methylation in Primate Liver and Skeletal Muscle

    PubMed Central

    Léger, Adrien; Le Guiner, Caroline; Nickerson, Michael L.; McGee Im, Kate; Ferry, Nicolas; Moullier, Philippe; Snyder, Richard O.; Penaud-Budloo, Magalie

    2011-01-01

    Recombinant adeno-associated viral (rAAV) vectors can support long-term transgene expression in quiescent tissues. Intramuscular (IM) administration of a single-stranded AAV vector (ssAAV) in the nonhuman primate (NHP) results in a peak protein level at 2–3 months, followed by a decrease over several months before reaching a steady-state. To investigate transgene expression and vector genome persistence, we previously demonstrated that rAAV vector genomes associate with histones and form a chromatin structure in NHP skeletal muscle more than one year after injection. In the mammalian nucleus, chromatin remodeling via epigenetic modifications plays key role in transcriptional regulation. Among those, CpG hyper-methylation of promoters is a known hallmark of gene silencing. To assess the involvement of DNA methylation on the transgene expression, we injected NHP via the IM or the intravenous (IV) route with a recombinant ssAAV2/1 vector. The expression cassette contains the transgene under the transcriptional control of the constitutive Rous Sarcoma Virus promoter (RSVp). Total DNA isolated from NHP muscle and liver biopsies from 1 to 37 months post-injection was treated with sodium bisulfite and subsequently analyzed by pyrosequencing. No significant CpG methylation of the RSVp was found in rAAV virions or in vector DNA isolated from NHP transduced tissues. Direct de novo DNA methylation appears not to be involved in repressing transgene expression in NHP after gene transfer mediated by ssAAV vectors. The study presented here examines host/vector interactions and the impact on transgene expression in a clinically relevant model. PMID:21687632

  13. TMEM5-associated dystroglycanopathy presenting with CMD and mild limb-girdle muscle involvement.

    PubMed

    Astrea, Guja; Pezzini, Ilaria; Picillo, Ester; Pasquariello, Rosa; Moro, Francesca; Ergoli, Manuela; D'Ambrosio, Paola; D'Amico, Adele; Politano, Luisa; Santorelli, Filippo Maria

    2016-07-01

    The dystroglycanopathies, which are caused by reduced glycosylation of alpha-dystroglycan, are a heterogeneous group of neurodegenerative disorders characterized by variable brain and skeletal muscle involvement. Recently, mutations in TMEM5 have been described in severe dystroglycanopathies. We present the clinical, molecular and neuroimaging features of an Italian boy who had delayed developmental milestones with mild limb-girdle muscle involvement, bilateral frontotemporal polymicrogyria, moderate intellectual disability, and no cerebellar involvement. He also presented a cochlear dysplasia and harbored a reported mutation (p.A47Rfs*42) in TMEM5, detected using targeted next-generation sequencing. The relatively milder muscular phenotype and associated structural brain abnormalities distinguish this case from previously reported patients with severe dystroglycanopathies and expand the spectrum of TMEM5-associated disorders. PMID:27212206

  14. Determination and depletion of residues of carbadox, tylosin, and virginiamycin in kidney, liver, and muscle of pigs in feeding experiments.

    PubMed

    Lauridsen, M G; Lund, C; Jacobsen, M

    1988-01-01

    The results of residue determinations of the growth promotors carbadox, tylosin, and virginiamycin in kidney, liver, and muscle from pigs in feeding experiments are described as well as the analytical methods used. Residues of the carbadox metabolite quinoxaline-2-carboxylic acid were found in liver from pigs fed 20 mg/kg in the diet with a withdrawal time of 30 days. No residues were detected in muscle with zero withdrawal time. The limit of determination was 0.01 mg/kg for both tissues. No residues of virginiamycin and tylosin were found in pigs fed 50 and 40 mg/kg, respectively, in the diet, even with zero withdrawal time. Residues of tylosin of 0.06 mg/kg and below were detected in liver and kidney from pigs fed 200 or 400 mg/kg and slaughtered within 3 h after the last feeding. PMID:3148611

  15. Identification, isolation and expansion of myoendothelial cells involved in leech muscle regeneration.

    PubMed

    Grimaldi, Annalisa; Banfi, Serena; Gerosa, Laura; Tettamanti, Gianluca; Noonan, Douglas M; Valvassori, Roberto; de Eguileor, Magda

    2009-01-01

    Adult skeletal muscle in vertebrates contains myoendothelial cells that express both myogenic and endothelial markers, and which are able to differentiate into myogenic cells to contribute to muscle regeneration. In spite of intensive research efforts, numerous questions remain regarding the role of cytokine signalling on myoendothelial cell differentiation and muscle regeneration. Here we used Hirudo medicinalis (Annelid, leech) as an emerging new model to study myoendothelial cells and muscle regeneration. Although the leech has relative anatomical simplicity, it shows a striking similarity with vertebrate responses and is a reliable model for studying a variety of basic events, such as tissue repair. Double immunohistochemical analysis were used to characterize myoendothelial cells in leeches and, by injecting in vivo the matrigel biopolymer supplemented with the cytokine Vascular Endothelial Growth Factor (VEGF), we were able to isolate this specific cell population expressing myogenic and endothelial markers. We then evaluated the effect of VEGF on these cells in vitro. Our data indicate that, similar to that proposed for vertebrates, myoendothelial cells of the leech directly participate in myogenesis both in vivo and in vitro, and that VEGF secretion is involved in the recruitment and expansion of these muscle progenitor cells. PMID:19876402

  16. Consumption of sucrose and high-fructose corn syrup does not increase liver fat or ectopic fat deposition in muscles.

    PubMed

    Bravo, Stephen; Lowndes, Joshua; Sinnett, Stephanie; Yu, Zhiping; Rippe, James

    2013-06-01

    It has been postulated that fructose-induced triglyceride synthesis is augmented when accompanied by glucose. Chronic elevations could lead to excess fat accumulation in the liver and ectopic fat deposition in muscles, which in turn could contribute to the induction of abnormalities in glucose homeostasis, insulin resistance, and the subsequent development of type 2 diabetes. Our objective was to evaluate the effect of the addition of commonly consumed fructose- and (or) glucose-containing sugars in the usual diet on liver fat content and intramuscular adipose tissue. For 10 weeks, 64 individuals (mean age, 42.16 ± 11.66 years) consumed low-fat milk sweetened with either high-fructose corn syrup (HFCS) or sucrose; the added sugar matched consumption levels of fructose in the 25th, 50th, and 90th percentiles of the population. The fat content of the liver was measured with unenhanced computed tomography imaging, and the fat content of muscle was assessed with magnetic resonance imaging. When the 6 HFCS and sucrose groups were averaged, there was no change over the course of 10 weeks in the fat content of the liver (13.32% ± 10.49% vs. 13.21% ± 10.75%; p > 0.05), vastus lateralis muscle (3.07 ± 0.74 g per 100 mL vs. 3.15 ± 0.84 g per 100 mL; p > 0.05), or gluteus maximus muscle (4.08 ± 1.50 g per 100 mL vs. 4.24 ± 1.42 g per 100 mL; p > 0.05). Group assignment did not affect the result (interaction > 0.05). These data suggest that when fructose is consumed as part of a typical diet in normally consumed sweeteners, such as sucrose or HFCS, ectopic fat storage in the liver or muscles is not promoted. PMID:23724887

  17. The transcriptome of muscle and liver is responding differently to a combined trenbolone acetate and estradiol implant in cattle.

    PubMed

    Elgendy, Ramy; Giantin, Mery; Montesissa, Clara; Dacasto, Mauro

    2016-02-01

    We investigated the transcriptomic signature of some anabolic steroids in cattle. Our main objective was to evaluate the effect of a combined trenbolone acetate (TBA, 200mg) and estradiol-17β (E2, 40 mg) implant (Revalor-XS®, REV) on the transcriptome of muscle (target tissue for anabolic steroids) and liver (main biotransformation site). Transcriptomic profiling was performed on 60 samples (30 per tissue) representing 2 groups of animals: REV (sustained release implant for 71 days, n=15), and a control group (CTR, n=15). The analyses (REV vs. CTR) evidenced the differential expression of 431 (down-regulated) and 503 transcripts (268 up-regulated and 235 down-regulated) in muscle and liver tissues, respectively. Functional annotation showed the enrichment of several ion transport systems (cation, metal ion and potassium ion transport) in muscle, while revealing the enrichment of carbohydrate, protein and glycoprotein metabolism and biosynthesis mechanisms in the liver. Both tissues had 20 genes commonly expressed in-between. Seven randomly-selected genes showed positive correlation with their corresponding microarray data upon a qPCR cross-validation step. In muscle, but not the liver, Principal Component Analysis (PCA) on the microarray data resulted in the separation of treated animals from the untreated ones (first 2 components=97.87%.). Overall, the identification of different genes, pathways and biological processes has illustrated the distinctive transcriptomic profile of muscle and liver in response to anabolic steroids. Moreover, it is becoming more clear that anabolic steroids are working through a complex interaction of numerous pathways and processes incorporating different tissues. PMID:26581765

  18. 1H-MRS Measured Ectopic Fat in Liver and Muscle in Danish Lean and Obese Children and Adolescents

    PubMed Central

    Fonvig, Cilius Esmann; Chabanova, Elizaveta; Andersson, Ehm Astrid; Ohrt, Johanne Dam; Pedersen, Oluf; Hansen, Torben; Thomsen, Henrik S.; Holm, Jens-Christian

    2015-01-01

    Objectives This cross sectional study aims to investigate the associations between ectopic lipid accumulation in liver and skeletal muscle and biochemical measures, estimates of insulin resistance, anthropometry, and blood pressure in lean and overweight/obese children. Methods Fasting plasma glucose, serum lipids, serum insulin, and expressions of insulin resistance, anthropometry, blood pressure, and magnetic resonance spectroscopy of liver and muscle fat were obtained in 327 Danish children and adolescents aged 8–18 years. Results In 287 overweight/obese children, the prevalences of hepatic and muscular steatosis were 31% and 68%, respectively, whereas the prevalences in 40 lean children were 3% and 10%, respectively. A multiple regression analysis adjusted for age, sex, body mass index z-score (BMI SDS), and pubertal development showed that the OR of exhibiting dyslipidemia was 4.2 (95%CI: [1.8; 10.2], p = 0.0009) when hepatic steatosis was present. Comparing the simultaneous presence of hepatic and muscular steatosis with no presence of steatosis, the OR of exhibiting dyslipidemia was 5.8 (95%CI: [2.0; 18.6], p = 0.002). No significant associations between muscle fat and dyslipidemia, impaired fasting glucose, or blood pressure were observed. Liver and muscle fat, adjusted for age, sex, BMI SDS, and pubertal development, associated to BMI SDS and glycosylated hemoglobin, while only liver fat associated to visceral and subcutaneous adipose tissue and intramyocellular lipid associated inversely to high density lipoprotein cholesterol. Conclusion Hepatic steatosis is associated with dyslipidemia and liver and muscle fat depositions are linked to obesity-related metabolic dysfunctions, especially glycosylated hemoglobin, in children and adolescents, which suggest an increased cardiovascular disease risk. PMID:26252778

  19. Fatty Acid Composition of Muscle, Adipose Tissue and Liver from Muskoxen (Ovibos moschatus) Living in West Greenland.

    PubMed

    Alves, Susana P; Raundrup, Katrine; Cabo, Ângelo; Bessa, Rui J B; Almeida, André M

    2015-01-01

    Information about lipid content and fatty acid (FA) composition of muskoxen (Ovibos moschatos) edible tissues is very limited in comparison to other meat sources. Thus, this work aims to present the first in-depth characterization of the FA profile of meat, subcutaneous adipose tissue and liver of muskoxen living in West Greenland. Furthermore, we aim to evaluate the effect of sex in the FA composition of these edible tissues. Samples from muscle (Longissimus dorsi), subcutaneous adipose tissue and liver were collected from female and male muskoxen, which were delivered at the butchery in Kangerlussuaq (West Greenland) during the winter hunting season. The lipid content of muscle, adipose tissue and liver averaged 284, 846 and 173 mg/g of dry tissue, respectively. This large lipid contents confirms that in late winter, when forage availability is scarce, muskoxen from West Greenland still have high fat reserves, demonstrating that they are well adapted to seasonal feed restriction. A detailed characterization of FA and dimethylacetal composition of muskoxen muscle, subcutaneous adipose tissue and liver showed that there are little differences on FA composition between sexes. Nevertheless, the 18:1cis-9 was the most abundant FA in muscle and adipose tissue, reaching 43% of total FA in muscle. The high content of 18:1cis-9 suggests that it can be selectively stored in muskoxen tissues. Regarding the nutritional composition of muskoxen edible tissues, they are not a good source of polyunsaturated FA; however, they may contribute to a higher fat intake. Information about the FA composition of muskoxen meat and liver is scarce, so this work can contribute to the characterization of the nutritional fat properties of muskoxen edible tissues and can be also useful to update food composition databases. PMID:26678792

  20. Fatty Acid Composition of Muscle, Adipose Tissue and Liver from Muskoxen (Ovibos moschatus) Living in West Greenland

    PubMed Central

    Alves, Susana P.; Raundrup, Katrine; Cabo, Ângelo; Bessa, Rui J. B.; Almeida, André M.

    2015-01-01

    Information about lipid content and fatty acid (FA) composition of muskoxen (Ovibos moschatos) edible tissues is very limited in comparison to other meat sources. Thus, this work aims to present the first in-depth characterization of the FA profile of meat, subcutaneous adipose tissue and liver of muskoxen living in West Greenland. Furthermore, we aim to evaluate the effect of sex in the FA composition of these edible tissues. Samples from muscle (Longissimus dorsi), subcutaneous adipose tissue and liver were collected from female and male muskoxen, which were delivered at the butchery in Kangerlussuaq (West Greenland) during the winter hunting season. The lipid content of muscle, adipose tissue and liver averaged 284, 846 and 173 mg/g of dry tissue, respectively. This large lipid contents confirms that in late winter, when forage availability is scarce, muskoxen from West Greenland still have high fat reserves, demonstrating that they are well adapted to seasonal feed restriction. A detailed characterization of FA and dimethylacetal composition of muskoxen muscle, subcutaneous adipose tissue and liver showed that there are little differences on FA composition between sexes. Nevertheless, the 18:1cis-9 was the most abundant FA in muscle and adipose tissue, reaching 43% of total FA in muscle. The high content of 18:1cis-9 suggests that it can be selectively stored in muskoxen tissues. Regarding the nutritional composition of muskoxen edible tissues, they are not a good source of polyunsaturated FA; however, they may contribute to a higher fat intake. Information about the FA composition of muskoxen meat and liver is scarce, so this work can contribute to the characterization of the nutritional fat properties of muskoxen edible tissues and can be also useful to update food composition databases. PMID:26678792

  1. Microcystin accumulation in liver and muscle of tilapia in two large Brazilian hydroelectric reservoirs.

    PubMed

    Deblois, Charles P; Aranda-Rodriguez, Rocio; Giani, Alessandra; Bird, David F

    2008-03-01

    The objective of this study was to measure levels of the toxin microcystin in different tissues of fish known to feed on cyanobacteria during toxic bloom events. Wild Nile and redbreast tilapia (Oreochromis niloticus and Tilapia rendalli) were sampled from the catch of artisanal fishermen at eutrophic stations of Funil and Furnas reservoirs in southeastern Brazil. Phytoplankton communities in the two reservoirs were quite different taxonomically, but not dissimilar in microcystin content (200 microg g dry weight (DW) seston(-1) at Funil, 800 microg gDW seston(-1) at Furnas). All of the 27 fish sampled contained microcystin, ranging from 0.8 to 32.1 microg g liver(-1) and from 0.9 to 12.0 ng g muscle(-1). Most microcystin variants found in seston were also found in fish liver. T. rendalli had the lowest concentration in both tissues when compared to O. niloticus. In both reservoirs, one of every four fish sampled, always O. niloticus, had a level of microcystins beyond the World Health Organization tolerable daily intake (8 ng g tissue(-1)) and represented a risk for consumers. It is possible that closer study of inter-species variability in toxin burden in cyanobacteria-impacted water bodies will permit the development of guidelines for fish consumption that will better protect public health. PMID:18067935

  2. In vivo measurement of nitric oxide production in porcine gut, liver and muscle during hyperdynamic endotoxaemia

    PubMed Central

    Bruins, Maaike J; Lamers, Wouter H; Meijer, Alfred J; Soeters, Peter B; Deutz, Nicolaas E P

    2002-01-01

    During prolonged endotoxaemia, an increase in arginine catabolism may result in limiting substrate availability for nitric oxide (NO) production. These effects were quantitated in a chronically instrumented porcine endotoxaemia model. Ten days prior to the beginning of the experiments, pigs were catheterized. On day 0, pigs received a continuous infusion of endotoxin (3 μg kg−1 h−1) over 24 h and were saline resuscitated. Blood was drawn from the catheters at 0 and 24 h during primed-infusion of 15N2-arginine and P-aminohippurate to assess 15N2-arginine to 15N-citrulline conversion and plasma flow rates, respectively, across the portal-drained viscera, liver and hindquarter. During endotoxin infusion a hyperdynamic circulation with elevated heart rate, cardiac index and decreased mean arterial pressure was achieved, characteristic of the human septic condition. Endotoxin induced NO production by the portal-drained viscera and the liver. The increased NO production was quantitatively matched by an increase in arginine disposal. Nitrite/nitrate levels remained unchanged during endotoxaemia. Despite an increased arginine production from the hindquarter and an increased whole-body arginine appearance rate during endotoxin infusion, the plasma arginine concentration was lower in endotoxin-treated animals than in controls. On a whole-body level, the muscle was found to serve as a major arginine supplier and, considering the lowered arginine plasma levels, seems critical in providing arginine as precursor for NO synthesis in the splanchnic region. PMID:12466232

  3. Liver involvement during influenza infection: perspective on the 2009 influenza pandemic

    PubMed Central

    Papic, Neven; Pangercic, Ana; Vargovic, Martina; Barsic, Bruno; Vince, Adriana; Kuzman, Ilija

    2011-01-01

    Please cite this paper as: Papic et al. (2011) Liver involvement during influenza infection: perspective on the 2009 influenza pandemic. Influenza and Other Respiratory Viruses 6(3), e2–e5. Elevation of liver transaminase levels is a frequent observation during systemic infections. The aim of our study was to investigate liver damage during pandemic 2009 influenza A/H1N1 infection in comparison with seasonal influenza. Serum levels of aspartate aminotransferase, alanine aminotransferase, and gamma‐glutamyl transpeptidase (GGT) were significantly higher in patients with pandemic influenza compared to seasonal influenza, which was strongly correlated with hypoxia. Moreover, a positive correlation between C‐reactive protein and serum GGT, alkaline phosphatase, and lactate dehydrogenase was noticed. Our findings support the hypothesis that the pandemic 2009 influenza A/H1N1 is an illness with a significant immune response to infection leading to hepatocellular injury. PMID:21951624

  4. Interleukin-13 is involved in the formation of liver fibrosis in Clonorchis sinensis-infected mice.

    PubMed

    Xu, Yanquan; Liang, Pei; Bian, Meng; Chen, Wenjun; Wang, Xiaoyun; Lin, Jinsi; Shang, Mei; Qu, Hongling; Wu, Zhongdao; Huang, Yan; Yu, Xinbing

    2016-07-01

    Clonorchiasis is a chronic infection disease often accompanied by formation of liver fibrosis. Previous study has identified that Clonorchis sinensis (C. sinensis, Cs) infection and CsRNASET2 (a member of CsESPs) immunization can drive Th2 immune response. IL-13, a multifunctional Th2 cytokine, has been widely confirmed to be profibrotic mediator. We want to determine whether IL-13 is involved in the generation of liver fibrosis during C. sinensis infection. A part of mice were infected with C. sinensis or immunized with CsRNASET2, respectively. Another part of mice were intravenously injected with rIL-13. Liver tissues of C. sinensis-infected mice were stained with hematoxylin-eosin and Masson's trichrome, respectively. The transcriptional levels of collagen-I, collagen-III, α-SMA, and TIMP-1 in the livers of infected mice and rIL-13-treated mice were measured by quantitative RT-PCR. Besides, splenocytes of C. sinensis-infected and CsRNASET2-immunized mice were isolated, respectively. The levels of IL-13 in splenocytes were detected by ELISA. Our results displayed that the livers of C. sinensis-infected mice had serious chronic inflammation and collagen deposition. The transcriptional levels of collagen-I, collagen-III, α-SMA, and TIMP-1 in the livers of C. sinensis-infected mice were obviously increased. Splenocytes from both C. sinensis-infected and CsRNASET2-immunized mice expressed high levels of IL-13. Moreover, rIL-13 treatment markedly promoted the transcriptional levels of collagen-I, collagen-III, α-SMA, and TIMP-1. These data implied that hepatic fibrosis was formed in the livers of C. sinensis-infected mice, and IL-13 induced by C. sinensis infection and CsRNASET2 immunization might favor this progression. PMID:26993324

  5. Systematic review of genetic association studies involving histologically confirmed non-alcoholic fatty liver disease

    PubMed Central

    Wood, Kayleigh L; Miller, Michael H; Dillon, John F

    2015-01-01

    Non-alcoholic fatty liver disease has an increasing prevalence in Western countries, affecting up to 20% of the population. Objective The aim of this project was to systematically review and summarise the genetic association studies that investigate possible genetic influences that confer susceptibility to non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Design The MEDLINE and SCOPUS databases were searched to identify candidate gene studies on histologically diagnosed non-alcoholic fatty liver disease. Results A total of 85 articles have been summarised and categorised on the basis of the general pathway each candidate gene is involved in, including lipid metabolism, lipoprotein processing, cholesterol synthesis, glucose homoeostasis, inflammatory response, protection against oxidative stress and whole body metabolism. Conclusions The main findings demonstrate a small but consistent association of PNPLA3 with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Genetic association studies have investigated general disease susceptibility, histological characteristics, severity and progression. However, further study is required to better elucidate the genetic factors influencing fatty liver disease. PMID:26462272

  6. Genetic, metabolic and environmental factors involved in the development of liver cirrhosis in Mexico

    PubMed Central

    Ramos-Lopez, Omar; Martinez-Lopez, Erika; Roman, Sonia; Fierro, Nora A; Panduro, Arturo

    2015-01-01

    Liver cirrhosis (LC) is a chronic illness caused by inflammatory responses and progressive fibrosis. Globally, the most common causes of chronic liver disease include persistent alcohol abuse, followed by viral hepatitis infections and nonalcoholic fatty liver disease. However, regardless of the etiological factors, the susceptibility and degree of liver damage may be influenced by genetic polymorphisms that are associated with distinct ethnic and cultural backgrounds. Consequently, metabolic genes are influenced by variable environmental lifestyle factors, such as diet, physical inactivity, and emotional stress, which are associated with regional differences among populations. This Topic Highlight will focus on the genetic and environmental factors that may influence the metabolism of alcohol and nutrients in the setting of distinct etiologies of liver disease. The interaction between genes and environment in the current-day admixed population, Mestizo and Native Mexican, will be described. Additionally, genes involved in immune regulation, insulin sensitivity, oxidative stress and extracellular matrix deposition may modulate the degree of severity. In conclusion, LC is a complex disease. The onset, progression, and clinical outcome of LC among the Mexican population are influenced by specific genetic and environmental factors. Among these are an admixed genome with a heterogenic distribution of European, Amerindian and African ancestry; a high score of alcohol consumption; viral infections; a hepatopathogenic diet; and a high prevalence of obesity. The variance in risk factors among populations suggests that intervention strategies directed towards the prevention and management of LC should be tailored according to such population-based features. PMID:26556986

  7. Genetic, metabolic and environmental factors involved in the development of liver cirrhosis in Mexico.

    PubMed

    Ramos-Lopez, Omar; Martinez-Lopez, Erika; Roman, Sonia; Fierro, Nora A; Panduro, Arturo

    2015-11-01

    Liver cirrhosis (LC) is a chronic illness caused by inflammatory responses and progressive fibrosis. Globally, the most common causes of chronic liver disease include persistent alcohol abuse, followed by viral hepatitis infections and nonalcoholic fatty liver disease. However, regardless of the etiological factors, the susceptibility and degree of liver damage may be influenced by genetic polymorphisms that are associated with distinct ethnic and cultural backgrounds. Consequently, metabolic genes are influenced by variable environmental lifestyle factors, such as diet, physical inactivity, and emotional stress, which are associated with regional differences among populations. This Topic Highlight will focus on the genetic and environmental factors that may influence the metabolism of alcohol and nutrients in the setting of distinct etiologies of liver disease. The interaction between genes and environment in the current-day admixed population, Mestizo and Native Mexican, will be described. Additionally, genes involved in immune regulation, insulin sensitivity, oxidative stress and extracellular matrix deposition may modulate the degree of severity. In conclusion, LC is a complex disease. The onset, progression, and clinical outcome of LC among the Mexican population are influenced by specific genetic and environmental factors. Among these are an admixed genome with a heterogenic distribution of European, Amerindian and African ancestry; a high score of alcohol consumption; viral infections; a hepatopathogenic diet; and a high prevalence of obesity. The variance in risk factors among populations suggests that intervention strategies directed towards the prevention and management of LC should be tailored according to such population-based features. PMID:26556986

  8. Enhanced insulin sensitivity in skeletal muscle and liver by physiological overexpression of SIRT6☆

    PubMed Central

    Anderson, Jason G.; Ramadori, Giorgio; Ioris, Rafael M.; Galiè, Mirco; Berglund, Eric D.; Coate, Katie C.; Fujikawa, Teppei; Pucciarelli, Stefania; Moreschini, Benedetta; Amici, Augusto; Andreani, Cristina; Coppari, Roberto

    2015-01-01

    Objective Available treatment for obesity and type 2 diabetes mellitus (T2DM) is suboptimal. Thus, identifying novel molecular target(s) exerting protective effects against these metabolic imbalances is of enormous medical significance. Sirt6 loss- and gain-of-function studies have generated confounding data regarding the role of this sirtuin on energy and glucose homeostasis, leaving unclear whether activation or inhibition of SIRT6 may be beneficial for the treatment of obesity and/or T2DM. Methods To address these issues, we developed and studied a novel mouse model designed to produce eutopic and physiological overexpression of SIRT6 (Sirt6BAC mice). These mutants and their controls underwent several metabolic analyses. These include whole-blood reverse phase high-performance liquid chromatography assay, glucose and pyruvate tolerance tests, hyperinsulinemic-euglycemic clamp assays, and assessment of basal and insulin-induced level of phosphorylated AKT (p-AKT)/AKT in gastrocnemius muscle. Results Sirt6BAC mice physiologically overexpress functionally competent SIRT6 protein. While Sirt6BAC mice have normal body weight and adiposity, they are protected from developing high-caloric-diet (HCD)-induced hyperglycemia and glucose intolerance. Also, Sirt6BAC mice display increased circulating level of the polyamine spermidine. The ability of insulin to suppress endogenous glucose production was significantly enhanced in Sirt6BAC mice compared to wild-type controls. Insulin-stimulated glucose uptake was increased in Sirt6BAC mice in both gastrocnemius and soleus muscle, but not in brain, interscapular brown adipose, or epididymal adipose tissue. Insulin-induced p-AKT/AKT ratio was increased in gastrocnemius muscle of Sirt6BAC mice compared to wild-type controls. Conclusions Our data indicate that moderate, physiological overexpression of SIRT6 enhances insulin sensitivity in skeletal muscle and liver, engendering protective actions against diet-induced T2DM. Hence

  9. Contribution of abnormal muscle and liver glucose metabolism to postprandial hyperglycemia in NIDDM

    SciTech Connect

    Mitrakou, A.; Kelley, D.; Veneman, T.; Jenssen, T.; Pangburn, T.; Reilly, J.; Gerich, J. )

    1990-11-01

    To assess the role of muscle and liver in the pathogenesis of postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM), we administered an oral glucose load enriched with (14C)glucose to 10 NIDDM subjects and 10 age- and weight-matched nondiabetic volunteers and compared muscle glucose disposal by measuring forearm balance of glucose, lactate, alanine, O2, and CO2. In addition, we used the dual-lable isotope method to compare overall rates of glucose appearance (Ra) and disappearance (Rd), suppression of endogenous glucose output, and splanchnic glucose sequestration. During the initial 1-1.5 h after glucose ingestion, plasma glucose increased by approximately 8 mM in NIDDM vs. approximately 3 mM in nondiabetic subjects (P less than 0.01); overall glucose Ra was nearly 11 g greater in NIDDM than nondiabetic subjects, but glucose Rd was not significantly different in NIDDM and nondiabetic subjects. The greater overall glucose Ra of NIDDM subjects was due to 6.8 g greater endogenous glucose output (13.7 +/- 1.1 vs. 6.8 +/- 1.0 g, P less than 0.01) and 3.8 g less oral glucose splanchnic sequestration of the oral load (31.4 +/- 1.5 vs. 27.5 +/- 0.9 g, P less than 0.05). Although glucose taken up by muscle was not significantly different in NIDDM and nondiabetic subjects (39.3 +/- 3.5 vs. 41.0 +/- 2.5 g/5 h), a greater amount of the glucose taken up by muscle in NIDDM was released as lactate and alanine (11.7 +/- 1.0 vs. 5.2 +/- 0.3 g in nondiabetic subjects, P less than 0.01), and less was stored (11.7 +/- 1.3 vs. 16.9 +/- 1.5 g, P less than 0.05). We conclude that increased systemic glucose delivery, due primarily to reduced suppression of endogenous hepatic glucose output and, to a lesser extent, reduced splanchnic glucose sequestration, is the predominant factor responsible for postprandial hyperglycemia in NIDDM.

  10. Changes induced by dietary energy intake and divergent selection for muscle fat content in rainbow trout (Oncorhynchus mykiss), assessed by transcriptome and proteome analysis of the liver

    PubMed Central

    Kolditz, Catherine-Ines; Paboeuf, Gilles; Borthaire, Maïena; Esquerré, Diane; SanCristobal, Magali; Lefèvre, Florence; Médale, Françoise

    2008-01-01

    Background Growing interest is turned to fat storage levels and allocation within body compartments, due to their impact on human health and quality properties of farm animals. Energy intake and genetic background are major determinants of fattening in most animals, including humans. Previous studies have evidenced that fat deposition depends upon balance between various metabolic pathways. Using divergent selection, we obtained rainbow trout with differences in fat allocation between visceral adipose tissue and muscle, and no change in overall body fat content. Transcriptome and proteome analysis were applied to characterize the molecular changes occurring between these two lines when fed a low or a high energy diet. We focused on the liver, center of intermediary metabolism and the main site for lipogenesis in fish, as in humans and most avian species. Results The proteome and transcriptome analyses provided concordant results. The main changes induced by the dietary treatment were observed in lipid metabolism. The level of transcripts and proteins involved in intracellular lipid transport, fatty acid biosynthesis and anti-oxidant metabolism were lower with the lipid rich diet. In addition, genes and proteins involved in amino-acid catabolism and proteolysis were also under expressed with this diet. The major changes related to the selection effect were observed in levels of transcripts and proteins involved in amino-acid catabolism and proteolysis that were higher in the fat muscle line than in the lean muscle line. Conclusion The present study led to the identification of novel genes and proteins that responded to long term feeding with a high energy/high fat diet. Although muscle was the direct target, the selection procedure applied significantly affected hepatic metabolism, particularly protein and amino acid derivative metabolism. Interestingly, the selection procedure and the dietary treatment used to increase muscle fat content exerted opposite effects on

  11. Comparison of mercury concentrations in liver, muscle, whole bodies, and composites of fish from the Red River of the North

    USGS Publications Warehouse

    Goldstein, Robert M.; Brigham, Mark E.; Stauffer, Joseph C.

    1996-01-01

    Carp (Cyprinus carpio) from four sites and channel catfish (Ictalurus punctatus) from one site in the Red River of the North in 1994 were analyzed for total mercury content. In carp, mercury concentrations differed among liver, muscle, and whole bodies (0.11, 0.31, and 0.18 µg/g wet weight, respectively), between large and small size groups, but not location. Mercury distribution in channel catfish tissues differed from that in carp. Liver and muscle tissue had similar mean concentrations; each was higher than whole-body concentrations (0.16, 0.18, and 0.11 µg/g, respectively). Mercury concentrations were not significantly different between the two size groups of channel catfish. Weighted-mean mercury concentrations from seven individual fish agreed closely (usually within 10%) with concentrations determined on physical composites of the same fish. The ratio of mercury in whole bodies to mercury in muscle was similar for both carp and channel catfish. Historical data indicate that this ratio may be applicable to other species and locations. The ratio of mercury in livers to whole bodies and muscle differed between carp and channel catfish, which may reflect physiological differences between different trophic groups.

  12. Accumulation of trace metals in the muscle and liver tissues of five fish species from the Persian Gulf.

    PubMed

    Agah, Homira; Leermakers, Martine; Elskens, Marc; Fatemi, S Mohamad Rez; Baeyens, Willy

    2009-10-01

    In this study, concentrations of 16 elements were quantified in muscles and livers of 141 fishes belonging to five commercially species. It was also our intention to evaluate potential risks to human health associated with seafood consumption. The grunt, flathead, greasy grouper, tiger-tooth croaker and silver pomfret fish species were obtained from Abadan, Deylam, Bushehr-Nirogah, Dayyer port, Lengeh port and Abbas port in Hormozgan, Bushehr and Khozesran provinces at the Iranian waters of the Persian Gulf. The contents of Al, As, Be, Cd, Cr, Co, Cu, Fe, Pb, Mn, Mo, Ni, Sb, Tl, V and Zn in fish muscles and livers were determined by Inductively Coupled Plasma Mass Spectrometry (ICP MS), after digestion in a CEM (Mars 5) microwave oven using nitric acid and hydrogen peroxide. Our results indicated that almost all metals were more accumulated in younger flathead, greasy grouper and tiger-tooth fishes. Contrary to the other fish species, grunt seems to stronger accumulating elements in the older fishes. Strong and positive correlations were observed in three or more of the fish species between V, Al, Fe, Tl, Co and Pb. The results confirmed that fish muscle and liver tissues appeared to be good bio-indicators for identification of coastal areas exposed to metallic contaminants. The results also showed that the element levels in the muscles of all fishes in our study were lower than the maximum allowable concentrations and pose no threat to public health, except for arsenic. PMID:18850288

  13. Insulin-induced hypoglycaemia is co-ordinately regulated by liver and muscle during acute and chronic insulin stimulation in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Polakof, Sergio; Skiba-Cassy, Sandrine; Choubert, Georges; Panserat, Stéphane

    2010-05-01

    The relative glucose intolerance of carnivorous fish species is often proposed to be a result of poor peripheral insulin action or possibly insulin resistance. In the present study, data from aortic cannulated rainbow trout receiving bovine insulin (75 mIU kg(-1)) injections show for the first time their ability to clear glucose in a very efficient manner. In another set of experiments, mRNA transcripts and protein phosphorylation status of proteins controlling glycaemia and glucose-related metabolism were studied during both acute and chronic treatment with bovine insulin. Our results show that fasted rainbow trout are well adapted at the molecular level to respond to increases in circulating insulin levels, and that this hormone is able to potentially improve glucose distribution and uptake by peripheral tissues. After acute insulin administration we found that to counter-regulate the insulin-induced hypoglycaemia, trout metabolism is strongly modified. This short-term, efficient response to hypoglycaemia includes a rapid, coordinated response involving the reorganization of muscle and liver metabolism. During chronic insulin treatment some of the functions traditionally attributed to insulin actions in mammals were observed, including increased mRNA levels of glucose transporters and glycogen storage (primarily in the muscle) as well as decreased mRNA levels of enzymes involved in de novo glucose production (in the liver). Finally, we show that the rainbow trout demonstrates most of the classic metabolic adjustments employed by mammals to efficiently utilize glucose in the appropriate insulin context. PMID:20400628

  14. Oxidative stress and antioxidant status in rat blood, liver and muscle: effect of dietary lipid, carnitine and exercise.

    PubMed

    Karanth, Jyothsna; Jeevaratnam, Kadirvelu

    2005-09-01

    The purpose of this study was to determine the effect of dietary fat, carnitine supplementation, and exercise on oxidative damage and antioxidant status. Male Wistar rats (60 days old) were fed diets containing either hydrogenated fat (HF) or peanut oil (PO) with or without 0.5 mg % (of dry diet) carnitine. The rats were given exercise, i.e. swimming for 60 minutes, for 6 days/week for 6 months under each dietary condition. The blood malondialdehyde (MDA) level was higher in PO-fed rats, more so in exercising ones, while the same was not altered in carnitine-supplemented rats irrespective of the dietary fat or physical activity. The MDA level was significantly decreased in muscle, while increased in liver, of carnitine-fed rats. The blood glutathione (GSH) level also significantly increased in exercising rats as compared to sedentary ones, while carnitine supplementation elevated it in all the groups. Exercise and carnitine supplementation significantly lowered GSH levels in liver while increasing it in muscle. The glutathione peroxidase (GPX) activity was significantly increased in blood and muscle from PO-fed exercising rats as compared to sedentary ones, while carnitine supplementation elevated GPX activity in all the groups. The liver and muscle catalase (CAT) activities were significantly increased in PO-fed exercising rats, while carnitine did not have any effect. The pro-oxidative effect of the monounsaturated fatty acid (MUFA)-rich PO diet and prolonged regular exercise was less pronounced due to augmented antioxidant enzymes, GPX and CAT, induced by training to protect against the oxidative stress, while carnitine supplementation could help to counter lipid peroxidation due to exercise through redistribution of GSH from liver to blood and muscle. PMID:16477765

  15. Determination of nifursol metabolites in poultry muscle and liver tissue. Development and validation of a confirmatory method.

    PubMed

    Mulder, P P J; Zuidema, T; Keestra, N G M; Kooij, P J F; Elbers, I J W; van Rhijn, J A

    2005-05-01

    A method is described for the identification and quantitative determination of 3,5-dinitrosalicylic acid hydrazide (DSH), the marker residue of nifursol metabolites in poultry (turkey, broiler) muscle and liver tissue. The method is based on the acid-catalysed hydrolysis of tissue-bound metabolites to free DSH and in situ derivatisation with 2-nitrobenzaldehyde to the corresponding nitrophenyl derivative NPDSH. A structural analogue of DSH, 4-hydroxy-3,5-dinitrobenzoic acid hydrazide (HBH) was synthesised to serve as an internal standard. The analytes were isolated from the matrix by liquid-liquid extraction with ethyl acetate. Determination was performed by LC-MS/MS with negative electrospray ionisation. The [M - H](+) ions of NPDSH and NPHBH at m/z 374 were fragmented by collision induced dissociation (CID) producing transition ions at m/z 182, 183 and 226. The transition ions at m/z 182 and 226 were selected for monitoring of NPDSH while the transition ion at m/z 183 was selected for NPHBH. The method has been validated according to the EU criteria of Commission Decision 2002/657/EC at 0.5, 1.0 and 1.5 microg kg(-1) in muscle and liver tissue. A decision limit (CC(alpha)) was obtained of 0.04 and 0.025 microg kg(-1) in muscle and liver, respectively. Similarly a detection capability (CC(beta)) was obtained of 0.10 and 0.05 microg kg(-1) in muscle and liver, respectively. The introduction of HBH as an internal standard did not lead to a significant improvement of the quantitative performance of the method. In fact for liver better performance characteristics were obtained when the IS was not taken into account. Nevertheless, as a qualitative marker for recovery, HBH could still be very useful in the analysis of unknown samples. PMID:15852149

  16. Depletion of selenium in blood, liver and muscle from beef heifers previously fed forages containing high levels of selenium.

    PubMed

    Benes, Sharon E; Robinson, Peter H; Cun, Grace S

    2015-12-01

    Beef heifers which had grazed 'Jose' tall wheatgrass (TWG; Thinopyrum ponticum var. 'Jose'; 10 heifers) and creeping wildrye (CWR; Leymus triticoides var. 'Rio'; 10 heifers) with high levels of Se (>2 mg/kg DM) due to growth in saline soils, accumulated high Se levels in blood, liver and muscle (Juchem et al., 2012). We determined the decrease in Se levels in blood, liver and muscle from these heifers, particularly the decrease of Se in muscle, in order to determine the maximum feeding length of a low Se diet (LSeD) required sustaining Se-enriched beef. Immediately after grazing, all heifers were fed a LSeD containing <0.30 mg/kg DM for 209 d. Blood, liver and muscle samples, as well as body weight (BW), were collected at the beginning and end of the LSeD feeding period and at intermediate times. After grazing, CWR and TWG heifers had similar BW, but TWG heifers had higher levels of Se in whole blood (1.19 versus 0.81 mg/L), liver (2.67 versus 2.12 mg/kg wet weight (WW)), and muscle tissue (0.87 versus 0.63 mg/kg WW) than CWR heifers. The Se levels decreased with exposure time to the LSeD and, at 82 d of feeding the LSeD, Se levels were 77 (liver), 49 (blood) and 31% (muscle) lower. The BW gains for both groups were ~0.5 kg/d during the first 82 d of feeding, but increased thereafter. Levels of Cu in serum (0.28 versus 0.50 mg/L) and liver (1.14 versus 22.9 mg/kg WW) were lower at the end of grazing in TWG heifers, and suggested a potential Cu deficiency. Grazing forages with high Se levels can result in Se-enriched beef, but a LSeD feeding period of <82 d is required to maintain enrichment. PMID:26247689

  17. Bovine sirtuins: initial characterization and expression of sirtuins 1 and 3 in liver, muscle, and adipose tissue.

    PubMed

    Ghinis-Hozumi, Y; González-Gallardo, A; González-Dávalos, L; Antaramian, A; Villarroya, F; Shimada, A; Varela-Echavarría, A; Mora, O

    2011-08-01

    Sirtuins, the mammalian homologs of the silent information regulator 2 gene of Saccharomyces cerevisiae, are members of the NAD(+)-dependent family of histone deacetylases. In vertebrates, 7 sirtuins have been described, with different cellular localizations and target proteins. Glucose and lipid metabolism are among the processes regulated by these enzymes. In ruminants, gluconeogenesis is the main biochemical pathway by which glucose is obtained. Because sirtuins in bovines have not been studied, the aim of this work was to obtain sequences coding for the 7 sirtuins and determine the expression patterns of sirtuin1 (Sirt1) and sirtuin3 (Sirt3) in the liver, muscle, and adipose tissue of calves and bulls. Using PCR amplification, we obtained sirtuin gene sequences and reported them to the National Center for Biotechnology Information GenBank. Characteristic sequence motifs corresponding to the sirtuin catalytic core domain were found, including the active and zinc-binding sites. Relative expression patterns of Sirt1 and Sirt3 in liver, muscle, and adipose tissue were quantified by real-time PCR, normalizing to the geometric mean of the housekeeping genes cyclophilin A and β-actin. Expression of Sirt1 was less in liver and muscle, whereas it was greater in adipose tissue of adult animals, with statistical differences (P=0.0071) only in the latter. In the case of Sirt3, expression was greater in all 3 adult tissues, but statistical differences were found only in liver (P=0.0141) and muscle (P=0.0017). The greatest expression was observed in liver for Sirt1 and in muscle for Sirt3, whereas the least expression was in muscle for Sirt1 and in adipose tissue for Sirt3. In other species, sirtuin expression (both Sirt1 and Sirt3) in liver is reported to be the greatest among these 3 tissues, a pattern different from what we measured. These differences in expression can be associated with metabolic differences between nonruminant and ruminant species. However, further

  18. Methylation changes in muscle and liver tissues of male and female mice exposed to acute and chronic low-dose X-ray-irradiation.

    PubMed

    Kovalchuk, Olga; Burke, Paula; Besplug, Jill; Slovack, Mark; Filkowski, Jody; Pogribny, Igor

    2004-04-14

    The biological and genetic effects of chronic low-dose radiation (LDR) exposure and its relationship to carcinogenesis have received a lot of attention in the recent years. For example, radiation-induced genome instability, which is thought to be a precursor of tumorogenesis, was shown to have a transgenerational nature. This indicates a possible involvement of epigenetic mechanisms in LDR-induced genome instability. Genomic DNA methylation is one of the most important epigenetic mechanisms. Existing data on radiation effects on DNA methylation patterns is limited, and no one has specifically studied the effects of the LDR. We report the first study of the effects of whole-body LDR exposure on global genome methylation in muscle and liver tissues of male and female mice. In parallel, we evaluated changes in promoter methylation and expression of the tumor suppressor gene p16(INKa) and DNA repair gene O(6)-methylguanine-DNA methyltransferase (MGMT). We observed different patterns of radiation-induced global genome DNA methylation in the liver and muscle of exposed males and females. We also found sex and tissue-specific differences in p16(INKa) promoter methylation upon LDR exposure. In male liver tissue, p16(INKa) promoter methylation was more pronounced than in female tissue. In contrast, no significant radiation-induced changes in p16(INKa) promoter methylation were noted in the muscle tissue of exposed males and females. Radiation also did not significantly affect methylation status of MGMT promoter. We also observed substantial sex differences in acute and chronic radiation-induced expression of p16(INKa) and MGMT genes. Another important outcome of our study was the fact that chronic low-dose radiation exposure proved to be a more potent inducer of epigenetic effects than the acute exposure. This supports previous findings that chronic exposure leads to greater genome destabilization than acute exposure. PMID:15063138

  19. Molecular characterization of argininosuccinate synthase and argininosuccinate lyase from the liver of the African lungfish Protopterus annectens, and their mRNA expression levels in the liver, kidney, brain and skeletal muscle during aestivation.

    PubMed

    Chng, You R; Ong, Jasmine L Y; Ching, Biyun; Chen, Xiu L; Wong, Wai P; Chew, Shit F; Ip, Yuen K

    2014-10-01

    Argininosuccinate synthase (Ass) and argininosuccinate lyase (Asl) are involved in arginine synthesis for various purposes. The complete cDNA coding sequences of ass and asl from the liver of Protopterus annectens consisted of 1,296 and 1,398 bp, respectively. Phylogenetic analyses revealed that the deduced Ass and Asl of P. annectens had close relationship with that of the cartilaginous fish Callorhinchus milii. Besides being strongly expressed in the liver, ass and asl expression were detectable in many tissues/organs. In the liver, mRNA expression levels of ass and asl increased significantly during the induction phase of aestivation, probably to increase arginine production to support increased urea synthesis. The increases in ass and asl mRNA expression levels during the prolonged maintenance phase and early arousal phase of aestivation could reflect increased demand on arginine for nitric oxide (NO) production in the liver. In the kidney, there was a significant decrease in ass mRNA expression level after 6 months of aestivation, indicating possible decreases in the synthesis and supply of arginine to other tissues/organs. In the brain, changes in ass and asl mRNA expression levels during the three phases of aestivation could be related to the supply of arginine for NO synthesis in response to conditions that resemble ischaemia and ischaemia-reperfusion during the maintenance and arousal phase of aestivation, respectively. The decrease in ass mRNA expression level, accompanied with decreases in the concentrations of arginine and NO, in the skeletal muscle of aestivating P. annectens might ameliorate the potential of disuse muscle atrophy. PMID:25034132

  20. Economic and production consequences of liver fluke disease in double-muscled fattening cattle.

    PubMed

    Genicot, B; Mouligneau, F; Lekeux, P

    1991-05-01

    The frequency of liver fluke disease in fattening units was determined by the analysis of random faeces samples issued from 1,513 Belgian White Blue bulls aged from 5 to 7 months and weighing from 200 to 300 kg. 12.5% of the investigated bulls were positive for liver fluke disease. These bulls were spread over 56.5% of the investigated fattening units. Furthermore the infestation rate varied from 0 to 33.3% inside the fattening units. In order to assess the economic consequences of bovine fascioliasis in double-muscled cattle and the beneficial effects of a treatment against such a disease, a trial including 30 Belgian White Blue bulls, weighing 365 +/- 9 kg and aged from 10 to 12 months, was conducted in a selected fattening unit. On the basis of faecal examinations, the 30 animals were subdivided in negative (group A; n = 10) and positive animals (n = 20) for fascioliasis, the latter being either treated with nitroxinil (group B; n = 10) or not (group C; n = 10) on day 0 of this trial which was conducted during 75 days. The daily body gains in group C (1.661 +/- 0.140 kg) were significantly lower than those in group A (1.975 +/- 0.120 kg). On the other hand there was no significant difference between the daily body gains registered in group B (1.960 +/- 0.085 kg) and A. The estimated financial loss, due to flukes and accounted on a 75 day-period, averaged 2,748 Belgian Francs per bull in group C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1858458

  1. Proteomic changes involved in tenderization of bovine Longissimus dorsi muscle during prolonged ageing.

    PubMed

    Polati, Rita; Menini, Michele; Robotti, Elisa; Millioni, Renato; Marengo, Emilio; Novelli, Enrico; Balzan, Stefania; Cecconi, Daniela

    2012-12-01

    To study proteomic changes involved in tenderization of bovine Longissimus dorsi four Charolaise heifers and four Charolaise bull's muscles were sampled at slaughter after early and long ageing (2-4°C for 12 and 26days respectively). Descriptive sensory evaluation of samples were performed and their tenderness evaluated by Warner-Bratzler shear force test. Protein composition of fresh muscle and of meat aged was analysed by cartesian and polar 2-D electrophoresis. Student's t-test and Ranking-PCA analyses were performed to detect proteomic modulation, and the selected protein spots were identified by nano-HPLC-Chip MS/MS. This research has demonstrated that there are no differences between proteomic patterns of male and females Longissimus dorsi muscle, and that the extension of ageing beyond 12days, did not brings any concrete advantage in terms of sensory quality. Furthermore, the data presented here demonstrated that meat maturation caused changes of the abundance of proteins involved in metabolic, structural, and stress related processes. PMID:22953957

  2. Involvement of IL-1 in the Maintenance of Masseter Muscle Activity and Glucose Homeostasis

    PubMed Central

    Chiba, Ko; Tsuchiya, Masahiro; Koide, Masashi; Hagiwara, Yoshihiro; Sasaki, Keiichi; Hattori, Yoshinori; Watanabe, Makoto; Sugawara, Shunji; Kanzaki, Makoto; Endo, Yasuo

    2015-01-01

    Physical exercise reportedly stimulates IL-1 production within working skeletal muscles, but its physiological significance remains unknown due to the existence of two distinct IL-1 isoforms, IL-1α and IL-1β. The regulatory complexities of these two isoforms, in terms of which cells in muscles produce them and their distinct/redundant biological actions, have yet to be elucidated. Taking advantage of our masticatory behavior (Restrained/Gnawing) model, we herein show that IL-1α/1β-double-knockout (IL-1-KO) mice exhibit compromised masseter muscle (MM) activity which is at least partially attributable to abnormalities of glucose handling (rapid glycogen depletion along with impaired glucose uptake) and dysfunction of IL-6 upregulation in working MMs. In wild-type mice, masticatory behavior clearly increased IL-1β mRNA expression but no incremental protein abundance was detectable in whole MM homogenates, whereas immunohistochemical staining analysis revealed that both IL-1α- and IL-1β-immunopositive cells were recruited around blood vessels in the perimysium of MMs after masticatory behavior. In addition to the aforementioned phenotype of IL-1-KO mice, we found the IL-6 mRNA and protein levels in MMs after masticatory behavior to be significantly lower in IL-1-KO than in WT. Thus, our findings confirm that the locally-increased IL-1 elicited by masticatory behavior, although present small in amounts, contributes to supporting MM activity by maintaining normal glucose homeostasis in these muscles. Our data also underscore the importance of IL-1-mediated local interplay between autocrine myokines including IL-6 and paracrine cytokines in active skeletal muscles. This interplay is directly involved in MM performance and fatigability, perhaps mediated through maintaining muscular glucose homeostasis. PMID:26599867

  3. MNGIE with lack of skeletal muscle involvement and a novel TP splice site mutation.

    PubMed

    Szigeti, K; Wong, L-J C; Perng, C-L; Saifi, G M; Eldin, K; Adesina, A M; Cass, D L; Hirano, M; Lupski, J R; Scaglia, F

    2004-02-01

    Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive multisystem disorder caused by thymidine phosphorylase (TP) deficiency, resulting in severe gastrointestinal dysmotility and skeletal muscle abnormalities. A patient is reported with a classical MNGIE clinical presentation but without skeletal muscle involvement at morphological, enzymatic, or mitochondrial DNA level, though gastrointestinal myopathy was present. MNGIE was diagnosed by markedly raised plasma thymidine and reduced thymidine phosphorylase activity. Molecular genetic analysis showed a homozygous novel splice site mutation in TP. On immunohistochemical studies there was marked TP expression in the CNS, in contrast to what has been observed in rodents. It is important to examine the most significantly affected tissue and to measure TP activity and plasma thymidine in order to arrive at an accurate diagnosis in this condition. PMID:14757860

  4. Levels of mercury in muscle and liver of star-spotted dogfish (Mustelus manazo) from the northern region of Japan: a comparison with spiny dogfish (Squalus acanthias).

    PubMed

    Endo, Tetsuya; Hisamichi, Yohsuke; Kimura, Osamu; Ogasawara, Hideki; Ohta, Chiho; Koga, Nobuyuki; Kato, Yoshihisa; Haraguchi, Koichi

    2013-04-01

    We analyzed mercury (Hg) concentrations in muscle and liver samples of star-spotted dogfish (Mustelus manazo) caught off the northern region of Japan and compared them with those of spiny dogfish (Squalus acanthias) caught in the same region. The average body length of male star-spotted dogfish specimens was significantly smaller than that of female specimens, reflecting the slower growth rate of male fish. Hg concentrations in liver and muscle increased with increases in body length and estimated age of both male and female star-spotted dogfish specimens. However, the relationships between Hg concentration in liver or muscle and body length or estimated age of male specimens differed markedly from those of female specimens, reflecting differences in growth rate and cessation of growth on reaching maturity. Marked increases in Hg concentration in liver of male and female star-spotted dogfish specimens were observed slightly later than increases in Hg concentration in muscle of those specimens due to growth cessation. These marked increases in Hg in liver may reflect increases in Hg due to the formation of mercury selenide. Similar results were previously reported in spiny dogfish specimens, except spiny dogfish showed only trace levels of Hg in liver (Endo et al., Chemosphere 77:1333-1337, 2009). The greater lipid content in liver and the larger liver size in spiny dogfish may explain the much lower levels of Hg observed in liver of spiny dogfish compared with those in the star-spotted dogfish. PMID:23271344

  5. Effects of sexual maturation and feeding level on fatty acid metabolism gene expression in muscle, liver, and visceral adipose tissue of diploid and triploid rainbow trout, Oncorhynchus mykiss.

    PubMed

    Manor, Meghan L; Cleveland, Beth M; Weber, Gregory M; Kenney, P Brett

    2015-01-01

    In many cultured fish species, such as salmonids, gonadal development occurs at the expense of stored energy and nutrients, including lipids. However, mechanisms regulating nutrient repartitioning during sexual maturation are not well understood. This study compared sexually maturing diploid (2N) and sterile triploid (3N) female rainbow trout to investigate effects of sexual maturation on expression of 35 genes involved in fatty acid metabolism, including genes within fatty acid synthesis, β-oxidation, and cofactors of the mTOR and PPAR signaling pathways, in liver, white muscle, and visceral adipose tissue. Diploid fish were fed at different rations (0.25% and 0.50% tank biomass, and satiation) to determine effects of ration on gene expression. Gene expression was affected by ration level only in white muscle; erk and acat2 had higher expression in fish fed higher rations. On the other hand, sexual maturation affected gene expression across all three tissue types. Data indicate 2N fish have higher expression of β-oxidation genes within white muscle and within visceral adipose tissue. These findings support enhanced fatty acid mobilization within these tissues during sexual maturation. Higher expression of fatty acid synthesis genes in 3N female liver is associated with higher expression of mTOR cofactors and pparγ, which reflects continued deposition of lipids in these fish. Furthermore, greater expression of genes involved in β-oxidation pathways across ration levels in 2N females suggests that sexual maturation and the associated maturation-related signals are stronger regulators of lipid metabolism-related genes rather the rations applied in the current study. PMID:25242626

  6. Myrtenal ameliorates hyperglycemia by enhancing GLUT2 through Akt in the skeletal muscle and liver of diabetic rats.

    PubMed

    Rathinam, Ayyasamy; Pari, Leelavinothan

    2016-08-25

    Insulin signaling pathway is an important role in glucose utilization in tissues. Our Previous study has established that myrtenal has antihyperglycemic effect against diabetic rats. The aim of this study was to explore the molecular mechanism of myrtenal in Streptozotocin-induced diabetic rats. Experimental diabetes was induced by single intraperitoneal injection of Streptozotocin (STZ) (40 mg/kg bw) in Wistar albino rats. Diabetic rats were administered myrtenal (80 mg/kg bw) for a period of 28 days. Diabetic rats showed an increased the levels of plasma glucose, decreased the levels of plasma insulin, down-regulation of insulin receptor substrate 2 (IRS2), Akt and glucose transporter 2 (GLUT2) in liver and insulin receptor substrate 2 (IRS2), Akt and glucose transporter 4 (GLUT4) protein expression in skeletal muscle. However, myrtenal treated diabetic rats revealed decreased the levels of plasma glucose, improved the plasma insulin levels, up-regulation of IRS2, Akt and GLUT2 in liver and IRS2, Akt and GLUT4 protein expression in skeletal muscle. The up-regulation of glucose transporters enhances the glucose uptake in liver and skeletal muscle. The histopathology and immunohistochemical analysis of the pancreas also corroborates with the above findings. Our findings suggest that myrtenal could be a potent phytochemical in the management of diabetes. PMID:27417257

  7. Heavy metals distribution in muscle, liver, kidney and gill of European catfish (Silurus glanis) from Italian Rivers.

    PubMed

    Squadrone, S; Prearo, M; Brizio, P; Gavinelli, S; Pellegrino, M; Scanzio, T; Guarise, S; Benedetto, A; Abete, M C

    2013-01-01

    The accumulation of heavy metals in freshwaters has direct consequences to man and ecosystem. Thus, in this study, the concentrations of mercury, cadmium, lead, arsenic and chromium in organs of the predator European catfish (Silurus glanis) were investigated. Samples were collected annually in five sites covering the area of the Po River (North Italy) between 2007 and 2009. Metals were differently distributed in the various organs, the highest concentrations of Hg were found in muscle and liver, Cd in kidney, Pb in gill and liver, as in muscle, and of Cr in gill and liver. Our survey found Hg exceeding the Maximum Levels (MLs) of 0.5 ppm in 18% of samples, while Pb and Cd were lower than the MLs set by European regulations in muscle tissues (1881/2006/EC and 629/2008/EC). Hg concentrations were significantly related to sampling stations studied, according to the presence of many industrial activities in the catchment area of Bormida and Tanaro Rivers. The finding that Hg did not fit food fish legislation limits indicated that S. glanis flesh might not be utilised for human consumption. A close monitoring of metals pollution is strongly recommended especially in piscivorous fish, cause their bioaccumulation capacity. PMID:22901372

  8. Microarray analysis of hepatic gene expression identifies new genes involved in steatotic liver

    PubMed Central

    Guillén, Natalia; Navarro, María A.; Arnal, Carmen; Noone, Enda; Arbonés-Mainar, José M.; Acín, Sergio; Surra, Joaquín C.; Muniesa, Pedro; Roche, Helen M.; Osada, Jesús

    2009-01-01

    Trans-10, cis-12-conjugated linoleic acid (CLA)-enriched diets promote fatty liver in mice, while cis-9, trans-11-CLA ameliorates this effect, suggesting regulation of multiple genes. To test this hypothesis, apoE-deficient mice were fed a Western-type diet enriched with linoleic acid isomers, and their hepatic gene expression was analyzed with DNA microarrays. To provide an initial screening of candidate genes, only 12 with remarkably modified expression between both CLA isomers were considered and confirmed by quantitative RT-PCR. Additionally mRNA expression of 15 genes involved in lipid metabolism was also studied. Ten genes (Fsp27, Aqp4, Cd36, Ly6d, Scd1, Hsd3b5, Syt1, Cyp7b1, and Tff3) showed significant associations among their expressions and the degree of hepatic steatosis. Their involvement was also analyzed in other models of steatosis. In hyperhomocysteinemic mice lacking Cbs gene, only Fsp27, Cd36, Scd1, Syt1, and Hsd3b5 hepatic expressions were associated with steatosis. In apoE-deficient mice consuming olive-enriched diet displaying reduction of the fatty liver, only Fsp27 and Syt1 expressions were found associated. Using this strategy, we have shown that expression of these genes is highly associated with hepatic steatosis in a genetic disease such as Cbs deficiency and in two common situations such as Western diets containing CLA isomers or a Mediterranean-type diet. Conclusion: The results highlight new processes involved in lipid handling in liver and will help to understand the complex human pathology providing new proteins and new strategies to cope with hepatic steatosis. PMID:19258494

  9. The TWEAK–Fn14 dyad is involved in age-associated pathological changes in skeletal muscle

    SciTech Connect

    Tajrishi, Marjan M.; Sato, Shuichi; Shin, Jonghyun; Zheng, Timothy S.; Burkly, Linda C.; Kumar, Ashok

    2014-04-18

    Highlights: • The levels of TWEAK receptor Fn14 are increased in skeletal muscle during aging. • Deletion of Fn14 attenuates age-associated skeletal muscle fiber atrophy. • Deletion of Fn14 inhibits proteolysis in skeletal muscle during aging. • TWEAK–Fn14 signaling activates transcription factor NF-κB in aging skeletal muscle. • TWEAK–Fn14 dyad is involved in age-associated fibrosis in skeletal muscle. - Abstract: Progressive loss of skeletal muscle mass and strength (sarcopenia) is a major clinical problem in the elderly. Recently, proinflammatory cytokine TWEAK and its receptor Fn14 were identified as key mediators of muscle wasting in various catabolic states. However, the role of the TWEAK–Fn14 pathway in pathological changes in skeletal muscle during aging remains unknown. In this study, we demonstrate that the levels of Fn14 are increased in skeletal muscle of 18-month old (aged) mice compared with adult mice. Genetic ablation of Fn14 significantly increased the levels of specific muscle proteins and blunted the age-associated fiber atrophy in mice. While gene expression of two prominent muscle-specific E3 ubiquitin ligases MAFBx and MuRF1 remained comparable, levels of ubiquitinated proteins and the expression of autophagy-related molecule Atg12 were significantly reduced in Fn14-knockout (KO) mice compared with wild-type mice during aging. Ablation of Fn14 significantly diminished the DNA-binding activity of transcription factor nuclear factor-kappa B (NF-κB), gene expression of various inflammatory molecules, and interstitial fibrosis in skeletal muscle of aged mice. Collectively, our study suggests that the TWEAK–Fn14 signaling axis contributes to age-associated muscle atrophy and fibrosis potentially through its local activation of proteolytic systems and inflammatory pathways.

  10. Novel nongenomic signaling by glucocorticoid may involve changes to liver membrane order in rainbow trout.

    PubMed

    Dindia, Laura; Murray, Josh; Faught, Erin; Davis, Tracy L; Leonenko, Zoya; Vijayan, Mathilakath M

    2012-01-01

    Stress-induced glucocorticoid elevation is a highly conserved response among vertebrates. This facilitates stress adaptation and the mode of action involves activation of the intracellular glucocorticoid receptor leading to the modulation of target gene expression. However, this genomic effect is slow acting and, therefore, a role for glucocorticoid in the rapid response to stress is unclear. Here we show that stress levels of cortisol, the primary glucocorticoid in teleosts, rapidly fluidizes rainbow trout (Oncorhynchus mykiss) liver plasma membranes in vitro. This involved incorporation of the steroid into the lipid domains, as cortisol coupled to a membrane impermeable peptide moiety, did not affect membrane order. Studies confirmed that cortisol, but not sex steroids, increases liver plasma membrane fluidity. Atomic force microscopy revealed cortisol-mediated changes to membrane surface topography and viscoelasticity confirming changes to membrane order. Treating trout hepatocytes with stress levels of cortisol led to the modulation of cell signaling pathways, including the phosphorylation status of putative PKA, PKC and AKT substrate proteins within 10 minutes. The phosphorylation by protein kinases in the presence of cortisol was consistent with that seen with benzyl alcohol, a known membrane fluidizer. Our results suggest that biophysical changes to plasma membrane properties, triggered by stressor-induced glucocorticoid elevation, act as a nonspecific stress response and may rapidly modulate acute stress-signaling pathways. PMID:23056491

  11. Mechanisms involved in the chemoprotective effects of rosemary extract studied in human liver and bronchial cells.

    PubMed

    Offord, E A; Macé, K; Avanti, O; Pfeifer, A M

    1997-03-19

    Natural polyphenols found in rosemary have not only potent antioxidant activities but also anticarcinogenic properties. We have studied some of the molecular mechanisms involved in their chemopreventive action using in vitro human liver and bronchial cell models. Rosemary extract, or its active components, carnosol or carnosic acid are potent inhibitors of DNA adduct formation induced by benzo(a)pyrene or aflatoxin B1. At least two mechanisms are involved in the anticarcinogenic action of rosemary extract: (i) inhibition of the metabolic activation of procarcinogens catalysed by the phase I cytochrome P450 enzymes; (ii) induction of the detoxification pathway catalysed by the phase II enzymes such as glutathione S-transferase. PMID:9103309

  12. Involvement of TGF-β1/Smad3 Signaling in Carbon Tetrachloride-Induced Acute Liver Injury in Mice

    PubMed Central

    Niu, Liman; Cui, Xueling; Qi, Yan; Xie, Dongxue; Wu, Qian; Chen, Xinxin; Ge, Jingyan; Liu, Zhonghui

    2016-01-01

    Transforming growth factor-beta1 (TGF-β1) is a major factor in pathogenesis of chronic hepatic injury. Carbon tetrachloride (CCl4) is a liver toxicant, and CCl4-induced liver injury in mouse is a classical animal model of chemical liver injury. However, it is still unclear whether TGF-β1 is involved in the process of CCl4-induced acute chemical liver injury. The present study aimed to evaluate the role of TGF-β1 and its signaling molecule Smad3 in the acute liver injury induce by CCl4. The results showed that CCl4 induced acute liver injury in mice effectively confirmed by H&E staining of liver tissues, and levels of not only liver injury markers serum ALT and AST, but also serum TGF-β1 were elevated significantly in CCl4-treated mice, compared with the control mice treated with olive oil. Our data further revealed that TGF-β1 levels in hepatic tissue homogenate increased significantly, and type II receptor of TGF-β (TβRII) and signaling molecules Smad2, 3, mRNA expressions and Smad3 and phospho-Smad3 protein levels also increased obviously in livers of CCl4-treated mice. To clarify the effect of the elevated TGF-β1/Smad3 signaling on CCl4-induced acute liver injury, Smad3 in mouse liver was overexpressed in vivo by tail vein injection of Smad3-expressing plasmids. Upon CCl4 treatment, Smad3-overexpressing mice showed more severe liver injury identified by H&E staining of liver tissues and higher serum ALT and AST levels. Simultaneously, we found that Smad3-overexpressing mice treated with CCl4 showed more macrophages and neutrophils infiltration in liver and inflammatory cytokines IL-1β and IL-6 levels increment in serum when compared with those in control mice treated with CCl4. Moreover, the results showed that the apoptosis of hepatocytes increased significantly, and apoptosis-associated proteins Bax, cytochrome C and the cleaved caspase 3 expressions were up-regulated in CCl4-treated Smad3-overexpressing mice as well. These results suggested that TGF

  13. A form of mitofusin 2 (Mfn2) lacking the transmembrane domains and the COOH-terminal end stimulates metabolism in muscle and liver cells.

    PubMed

    Segalés, Jessica; Paz, José C; Hernández-Alvarez, María Isabel; Sala, David; Muñoz, Juan Pablo; Noguera, Eduard; Pich, Sara; Palacín, Manuel; Enríquez, José Antonio; Zorzano, Antonio

    2013-11-15

    Mitofusin 2 (Mfn2), a protein that participates in mitochondrial fusion, is required to maintain normal mitochondrial metabolism in skeletal muscle and liver. Given that muscle Mfn2 is repressed in obese or type 2 diabetic subjects, this protein may have a potential pathophysiological role in these conditions. To evaluate whether the metabolic effects of Mfn2 can be dissociated from its function in mitochondrial dynamics, we studied a form of human Mfn2, lacking the two transmembrane domains and the COOH-terminal coiled coil (ΔMfn2). This form localized in mitochondria but did not alter mitochondrial morphology in cells or in skeletal muscle fibers. The expression of ΔMfn2 in mouse skeletal muscle stimulated glucose oxidation and enhanced respiratory control ratio, which occurred in the absence of changes in mitochondrial mass. ΔMfn2 did not stimulate mitochondrial respiration in Mfn2-deficient muscle cells. The expression of ΔMfn2 in mouse liver or in hepatoma cells stimulated gluconeogenesis. In addition, ΔMfn2 activated basal and maximal respiration both in muscle and liver cells. In all, we show that a form of Mfn2 lacking mitochondrial fusion activity stimulates mitochondrial function and enhances glucose metabolism in muscle and liver tissues. This study suggests that Mfn2 regulates metabolism independently of changes in mitochondrial morphology. PMID:23941871

  14. Cadmium and lead in animal tissue (muscle, liver and kidney), cow milk and dairy products in Korea.

    PubMed

    Kim, Dong-Gyu; Kim, MeeKyung; Shin, Jin Young; Son, Seong-Wan

    2016-03-01

    A survey of Cd and Pb in animal tissue, milk and dairy products was conducted. Muscle, liver and kidney of domestically produced cows, pigs, chickens and ducks were collected from eight regions in Korea. Raw cow milk was collected from 9 regions, and imported dairy products (butter, cheese, cream and powdered milk) were collected from 15 countries. Cd and Pb were analysed by inductively coupled plasma mass spectrometry (ICP-MS) after microwave digestion. Concentrations of Cd and Pb did not exceed the Korean legal maximum levels in any of the samples. Correlation coefficients were estimated between concentration of Cd or Pb and animal age and between muscle, liver and kidney. In cows, there were good correlations between age and Cd in kidney (r = 0.748) and between Cd in liver and in kidney (r = 0.878). Continuous monitoring will be an important role to safeguard consumers in the event of a food contamination incident. PMID:26588172

  15. Thermoregulatory uncoupling in heart muscle mitochondria: involvement of the ATP/ADP antiporter and uncoupling protein.

    PubMed

    Simonyan, R A; Skulachev, V P

    1998-09-25

    Possible involvement of the ATP/ADP antiporter and uncoupling protein (UCP) in thermoregulatory uncoupling of oxidative phosphorylation in heart muscle has been studied. To this end, effects of carboxyatractylate (cAtr) and GDP, specific inhibitors of the antiporter and UCP, on the membrane potential of the oligomycin-treated mitochondria from cold-exposed (6 degrees C, 48 h) and control rats have been measured. It is found that cAtr increases the membrane potential level in both cold-exposed and non-exposed groups, the effect being strongly enhanced by cooling. As for GDP, it is effective only in mitochondria from the cold-exposed rats. In these mitochondria, the coupling effect of GDP is smaller than that of cAtr. CDP, which does not interact with UCP, is without any influence on membrane potential. The cold exposure is found to increase the uncoupling efficiency of added natural (palmitate) or artificial (SF6847) uncouplers, the increase being cAtr- and GDP-sensitive in the case of palmitate. The fatty acid-free bovine serum albumin enhances delta psi in both cold-exposed and control groups, the effect being much larger in the former case. It is concluded that in heart muscle mitochondria the ATP/ADP antiporter is responsible for the 'mild uncoupling' under normal conditions and for major portion of the thermoregulatory uncoupling in the cold whereas the rest of thermoregulatory uncoupling is served by UCP (presumably by UCP2 since the UCP2 mRNA level is shown to strongly increase in rat heart muscle under the cold exposure conditions used). PMID:9771898

  16. Molecular mechanisms involved in muscle wasting in cancer and ageing: cachexia versus sarcopenia.

    PubMed

    Argilés, Josep M; Busquets, Sílvia; Felipe, Antonio; López-Soriano, Francisco J

    2005-05-01

    The aim of the present review is to summarize and evaluate the different mechanisms and catabolic mediators involved in cancer cachexia and ageing sarcopenia since they may represent targets for future promising clinical investigations. Cancer cachexia is a syndrome characterized by a marked weight loss, anorexia, asthenia and anemia. In fact, many patients who die with advanced cancer suffer from cachexia. The degree of cachexia is inversely correlated with the survival time of the patient and it always implies a poor prognosis. Unfortunately, at the clinical level, cachexia is not treated until the patient suffers from a considerable weight loss and wasting. At this point, the cachectic syndrome is almost irreversible. The cachectic state is often associated with the presence and growth of the tumour and leads to a malnutrition status due to the induction of anorexia. In recent years, age-related diseases and disabilities have become of major health interest and importance. This holds particularly for muscle wasting, also known as sarcopenia, that decreases the quality of life of the geriatric population, increasing morbidity and decreasing life expectancy. The cachectic factors (associated with both depletion of fat stores and muscular tissue) can be divided into two categories: of tumour origin and humoural factors. In conclusion, more research should be devoted to the understanding of muscle wasting mediators, both in cancer and ageing, in particular the identification of common mediators may prove as a good therapeutic strategies for both prevention and treatment of wasting both in disease and during healthy ageing. PMID:15743680

  17. Identification of the human liver enzymes involved in the metabolism of the antimigraine agent almotriptan.

    PubMed

    Salva, Miquel; Jansat, Josep M; Martinez-Tobed, Antonio; Palacios, Jose M

    2003-04-01

    Almotriptan is a novel highly selective 5-hydroxytryptamine(1B/1D) agonist developed for the acute oral treatment of migraine. The in vitro metabolism of almotriptan has been investigated using human liver subcellular fractions and cDNA-expressed human enzymes, to study the metabolic pathways and identify the enzymes responsible for the formation of the major metabolites. Specific enzymes were identified by correlation analysis, chemical inhibition studies, and incubation with various cDNA expressed human enzymes. Human liver microsomes and S9 fraction metabolize almotriptan by 2-hydroxylation of the pyrrolidine group to form a carbinolamine metabolite intermediate, a reaction catalyzed by CYP3A4 and CYP2D6. This metabolite is further oxidized by aldehyde dehydrogenase to the open ring gamma-aminobutyric acid metabolite. Almotriptan is also metabolized at the dimethylaminoethyl group by N-demethylation, a reaction that is carried out by five different cytochrome P450s, flavin monooxygenase-3 mediated N-oxidation, and MAO-A catalyzed oxidative deamination to form the indole acetic acid and the indole ethyl alcohol derivatives of almotriptan. The use of human liver mitochondria confirmed the contribution of MAO-A to the metabolism of almotriptan. Both, the gamma-aminobutyric acid and the indole acetic acid metabolites have been found to be the major in vivo metabolites of almotriptan in humans. In addition, different clinical trials conducted to study the effects of CYP3A4, CYP2D6, and MAO-A on the pharmacokinetics of almotriptan confirmed the involvement of these enzymes in the metabolic clearance of this drug and that no dose changes are required in the presence of inhibitors of these enzymes. PMID:12642466

  18. Elucidating Molecular Networks That Either Affect or Respond to Plasma Cortisol Concentration in Target Tissues of Liver and Muscle

    PubMed Central

    Ponsuksili, Siriluck; Du, Yang; Murani, Eduard; Schwerin, Manfred; Wimmers, Klaus

    2012-01-01

    Cortisol is a steroid hormone with important roles in regulating immune and metabolic functions and organismal responses to external stimuli are mediated by the glucocorticoid system. Dysregulation of the afferent and efferent axis of glucocorticoid signaling have adverse effects on growth, health status, and well-being. Glucocorticoid secretion and signaling show large interindividual variation that has a considerable genetic component; however, little is known about the underlying genetic variants. Here, we used trait-correlated expression analysis, screening for expression quantitative trait loci (eQTL), genome-wide association (GWA) studies, and causality modeling to identify candidate genes in porcine liver and muscle that affect or respond to plasma cortisol levels. Through trait-correlated expression, we characterized transcript activities in many biological functions in liver and muscle. Candidates from the list of trait-correlated expressed genes were narrowed using only those genes with an eQTL, and these were further prioritized by determining whether their expression was predicted to be related to variation in plasma cortisol levels. Using network edge orienting (NEO), a causality modeling algorithm, 26 of 990 candidates in liver were predicted to affect and 70 to respond to plasma cortisol levels. Of 593 candidates in muscle that were correlated with cortisol levels and were regulated by eQTL, 2 and 25 were predicted as effective and responsive, respectively, to plasma cortisol levels. Comprehensive data integration has helped to elucidate the complex molecular networks contributing to cortisol levels and thus its subsequent metabolic effects. The discrimination of up- and downstream effects of transcripts affecting or responding to plasma cortisol concentrations improves the understanding of the biology of complex traits related to growth, health, and well-being. PMID:22904034

  19. Differential Fmo3 Gene Expression in Various Liver Injury Models Involving Hepatic Oxidative Stress in Mice

    PubMed Central

    Rudraiah, Swetha; Moscovitz, Jamie E.; Donepudi, Ajay C.; Campion, Sarah N.; Slitt, Angela L.; Aleksunes, Lauren M.; Manautou, José E.

    2015-01-01

    treatment in mice markedly increasedFmo3 gene expression. While BDL increased Fmo3 mRNA expression, protein level did not change. The discrepancy with Fmo3 induction in cholestatic models, ANIT and BDL, is not entirely clear. Results from Nrf2 KO mice with APAP suggest that the transcriptional regulation of Fmo3 during liver injury may not involve Nrf2. PMID:25193093

  20. Stromal Derived Factor-1/CXCR4 Axis Involved in Bone Marrow Mesenchymal Stem Cells Recruitment to Injured Liver

    PubMed Central

    Xiao Ling, Kuai; Peng, Li; Jian Feng, Zhang; Wei, Cao; Wei Yan, Yuan; Nan, Shao; Cheng Qi, Guan; Zhi Wei, Wang

    2016-01-01

    The molecular mechanism of bone marrow mesenchymal stromal stem cells (BMSCs) mobilization and migration to the liver was poorly understood. Stromal cell-derived factor-1 (SDF-1) participates in BMSCs homing and migration into injury organs. We try to investigate the role of SDF-1 signaling in BMSCs migration towards injured liver. The expression of CXCR4 in BMSCs at mRNA level and protein level was confirmed by RT-PCR, flow cytometry, and immunocytochemistry. The SDF-1 or liver lysates induced BMSCs migration was detected by transwell inserts. CXCR4 antagonist, AMD3100, and anti-CXCR4 antibody were used to inhibit the migration. The Sprague-Dawley rat liver injury model was established by intraperitoneal injection of thioacetamide. The concentration of SDF-1 increased as modeling time extended, which was determined by ELISA method. The Dir-labeled BMSCs were injected into the liver of the rats through portal vein. The cell migration in the liver was tracked by in vivo imaging system and the fluorescent intensity was measured. In vivo, BMSCs migrated into injured liver which was partially blocked by AMD3100 or anti-CXCR4 antibody. Taken together, the results demonstrated that the migration of BMSCs was regulated by SDF-1/CXCR4 signaling which involved in BMSCs recruitment to injured liver. PMID:26880995

  1. Colon cancer metastasis to mediastinal lymph nodes without liver or lung involvement: A case report.

    PubMed

    El-Halabi, Mustapha M; Chaaban, Said A; Meouchy, Joseph; Page, Seth; Salyers, William J

    2014-11-01

    Colon cancer is the second most common type of cancer in females and the third in males, worldwide. The most common sites of colon cancer metastasis are the regional lymph nodes, liver, lung, bone and brain. In this study, an extremely rare case of colon adenocarcinoma with extensive metastasis to the mediastinal lymph nodes without any other organ involvement is presented. A 44-year-old Caucasian male presented with abdominal pain, a change in bowel habits, melena and weight loss. Colonoscopy revealed a large friable, ulcerated, circumferential mass in the ascending colon. Biopsies were consistent with the diagnosis of invasive moderately differentiated adenocarcinoma. Subsequently, right colon resection was performed, and pathological analysis revealed moderately differentiated adenocarcinoma of the right colon with extensive regional lymph node involvement. Computed tomography (CT) scans of the chest, abdomen and pelvis were performed preoperatively as part of routine staging for colon cancer. No liver or lung pathology was identified; however, multiple pathologically enlarged mediastinal lymph nodes were observed. Endoscopic ultrasound with fine needle aspiration of the largest mediastinal lymph node, which measured 5.2×3.5 cm on CT scans, was performed. The pathology was again consistent with the diagnosis of metastatic colorectal primary adenocarcinoma. At present, no optimum treatment has been identified for metastatic colon cancer to the mediastinal lymph nodes. The patient in the current case received chemotherapy with folinic acid, fluorouracil and oxaliplatin (FOLFOX), as well as with bevacizumab. Initial follow-up CT scans of the chest revealed a positive response to treatment. Physicians, in particular, radiologists, must consider the mediastinum during the first evaluation and further follow-up of patients with colorectal carcinoma even in the absence of metastasis. PMID:25289100

  2. Sublethal toxicity of commercial formulations of deltamethrin and permethrin on selected biochemical constituents and enzyme activities in liver and muscle tissues of Anabas testudineus.

    PubMed

    Sapana Devi, Maisnam; Gupta, Abhik

    2014-10-01

    The freshwater fish Anabas testudineus was exposed for 21 days to two commercial formulations of synthetic pyrethroids deltamethrin and permethrin at sublethal concentrations of 0.007 and 0.0007 mg L(-1), and 0.093 and 0.0093 mg L(-1), that represented 10% and 1%, respectively, of the 96 h LC50 of these two pesticides for this fish. The glycogen, protein and lactic acid contents, along with succinate dehydrogenase (SDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) enzyme activities in liver and muscle tissues of control and pesticide-exposed fish were estimated. When compared with those of control fish, significant depletion of glycogen content was observed in liver, and that of protein in muscle tissue of fish treated with both the pesticides at their higher as well as lower concentrations. Lactic acid reduction was significant only in fish muscle treated with deltamethrin. SDH level was reduced significantly in both liver and muscle tissues except in fish exposed to 0.0093 mg L(-1) permethrin. AST level was reduced significantly in liver and muscle tissues and ALT in muscle tissue of deltamethrin treated fish only. It is concluded that deltamethrin, a type-II pyrethroid, is more toxic to fish than the type-I pyrethroid permethrin and is capable of rendering toxicity at a dose as low as 1% of its LC50 value. PMID:25307465

  3. Insulin signaling in skeletal muscle and liver of neonatal pigs during endotoxemia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sepsis has been associated with tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO) overproduction, insulin resistance, and a profound suppression of muscle protein synthesis. However, lesser suppression of muscle protein synthesis in neonatal pigs occurs in response to endotoxin (LPS) whe...

  4. Three days of intermittent stretching after muscle disuse alters the proteins involved in force transmission in muscle fibers in weanling rats

    PubMed Central

    Gianelo, M.C.S.; Polizzelo, J.C.; Chesca, D.; Mattiello-Sverzut, A.C.

    2015-01-01

    The aim of this study was to determine the effects of intermittent passive manual stretching on various proteins involved in force transmission in skeletal muscle. Female Wistar weanling rats were randomly assigned to 5 groups: 2 control groups containing 21- and 30-day-old rats that received neither immobilization nor stretching, and 3 test groups that received 1) passive stretching over 3 days, 2) immobilization for 7 days and then passive stretching over 3 days, or 3) immobilization for 7 days. Maximal plantar flexion in the right hind limb was imposed, and the stretching protocol of 10 repetitions of 30 s stretches was applied. The soleus muscles were harvested and processed for HE and picrosirius staining; immunohistochemical analysis of collagen types I, III, IV, desmin, and vimentin; and immunofluorescence labeling of dystrophin and CD68. The numbers of desmin- and vimentin-positive cells were significantly decreased compared with those in the control following immobilization, regardless of whether stretching was applied (P<0.05). In addition, the semi-quantitative analysis showed that collagen type I was increased and type IV was decreased in the immobilized animals, regardless of whether the stretching protocol was applied. In conclusion, the largest changes in response to stretching were observed in muscles that had been previously immobilized, and the stretching protocol applied here did not mitigate the immobilization-induced muscle changes. Muscle disuse adversely affected several proteins involved in the transmission of forces between the intracellular and extracellular compartments. Thus, the 3-day rehabilitation period tested here did not provide sufficient time for the muscles to recover from the disuse maladaptations in animals undergoing postnatal development. PMID:26648091

  5. Relaxin protects cardiac muscle cells from hypoxia/reoxygenation injury: involvement of the Notch-1 pathway.

    PubMed

    Boccalini, Giulia; Sassoli, Chiara; Formigli, Lucia; Bani, Daniele; Nistri, Silvia

    2015-01-01

    In animal models, the cardiotropic hormone relaxin has been shown to protect the heart against ischemia and reperfusion-induced damage, acting by multiple mechanisms that primarily involve the coronary vessels. This in vitro study evaluates whether relaxin also has a direct protective action on cardiac muscle cells. H9c2 rat cardiomyoblasts and primary mouse cardiomyocytes were subjected to hypoxia and reoxygenation. In some experiments, relaxin was added preventatively before hypoxia; in others, at reoxygenation. To elucidate its mechanisms of action, we focused on Notch-1, which is involved in heart pre- and postconditioning to ischemia. Inactivated RLX was used as negative control. Relaxin (17 nmol/L, EC50 4.7 nmol/L), added 24 h before hypoxia or at reoxygenation, protected against cardiomyocyte injury. In fact, relaxin significantly increased cell viability (assayed by trypan blue and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), decreased apoptosis (assayed by TUNEL and bax/bcl-2 ratio), and reduced nitroxidative damage (assayed by nitrotyrosine expression and 8-hydroxy-deoxyguanosine levels). These effects were partly attributable to the ability of relaxin to upregulate Notch-1 signaling; indeed, blockade of Notch-1 activation with the specific inhibitor DAPT reduced relaxin-induced cardioprotection during hypoxia and reoxygenation. This study adds new mechanistic insights on the cardioprotective role of relaxin on ischemic and oxidative damage. PMID:25342127

  6. Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability

    PubMed Central

    Ahmed, Naghia; Ronchi, Dario; Comi, Giacomo Pietro

    2015-01-01

    Replication and maintenance of mtDNA entirely relies on a set of proteins encoded by the nuclear genome, which include members of the core replicative machinery, proteins involved in the homeostasis of mitochondrial dNTPs pools or deputed to the control of mitochondrial dynamics and morphology. Mutations in their coding genes have been observed in familial and sporadic forms of pediatric and adult-onset clinical phenotypes featuring mtDNA instability. The list of defects involved in these disorders has recently expanded, including mutations in the exo-/endo-nuclease flap-processing proteins MGME1 and DNA2, supporting the notion that an enzymatic DNA repair system actively takes place in mitochondria. The results obtained in the last few years acknowledge the contribution of next-generation sequencing methods in the identification of new disease loci in small groups of patients and even single probands. Although heterogeneous, these genes can be conveniently classified according to the pathway to which they belong. The definition of the molecular and biochemical features of these pathways might be helpful for fundamental knowledge of these disorders, to accelerate genetic diagnosis of patients and the development of rational therapies. In this review, we discuss the molecular findings disclosed in adult patients with muscle pathology hallmarked by mtDNA instability. PMID:26251896

  7. Impact of dietary fatty acids on muscle composition, liver lipids, milt composition and sperm performance in European eel.

    PubMed

    Butts, Ian Anthony Ernest; Baeza, Rosa; Støttrup, Josianne Gatt; Krüger-Johnsen, Maria; Jacobsen, Charlotte; Pérez, Luz; Asturiano, Juan F; Tomkiewicz, Jonna

    2015-05-01

    In order for European eel aquaculture to be sustainable, the life cycle should be completed in captivity. Development of broodstock diets may improve the species' reproductive success in captivity, through the production of high-quality gametes. Here, our aim was to evaluate the influence of dietary regime on muscle composition, and liver lipids prior to induced maturation, and the resulting sperm composition and performance. To accomplish this fish were reared on three "enhanced" diets and one commercial diet, each with different levels of fatty acids, arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Neutral lipids from the muscle and liver incorporated the majority of the fatty acid profile, while phospholipids incorporated only certain fatty acids. Diet had an effect on the majority of sperm fatty acids, on the total volume of extractable milt, and on the percentage of motile sperm. Here, our results suggest that the total volume of extractable milt is a DHA-dependent process, as we found the diets with the highest DHA levels induced the most milt while the diet with the lowest DHA level induced the least amount of milt. The diet with the highest level of ARA induced medium milt volumes but had the highest sperm motility. EPA also seems important for sperm quality parameters since diets with higher EPA percentages had a higher volume of milt and higher sperm motility. In conclusion, dietary fatty acids had an influence on fatty acids in the tissues of male eel and this impacted sperm performance. PMID:25638567

  8. Biomarkers of oxidative stress and tissue damage released by muscle and liver after a single bout of swimming exercise.

    PubMed

    Ramos, Dionizio; Martins, Eduarda Gabrielle; Viana-Gomes, Diego; Casimiro-Lopes, Gustavo; Salerno, Verônica P

    2013-05-01

    Both acute exercise and excessive training can cause oxidative stress. The resulting increase in free radicals and the inadequate response from antioxidant systems can lead to a framework of cellular damage. An association between affected tissue and the biomarkers of oxidative stress that appear in plasma has not been clearly established. The aim of this study was to evaluate the source of oxidative stress biomarkers found in the plasma of untrained rats after a single bout of swimming exercise at 2 different intensities: low intensity (SBLIE) or high intensity (SBHIE). Immediately after the exercise, aspartate transaminase (AST), alanine transaminase (ALT), γ-glutamyltransferase (GGT), and lactate dehydrogenase (LDH) were measured in plasma to characterize cell damage. Oxidative stress was assessed using protein carbonylation (PC), total antioxidant capacity (TAC), and thiobarbituric acid reactive substances (TBARS) quantified by malondialdehyde concentration. SBHIE raised levels of plasma AST (93%) and ALT (17%), and both exercise regimens produced an increase in GGT (7%) and LDH (∼55%). Plasma levels of PC and TBARS were greater in the SBHIE group; there were no changes in TAC. SBLIE caused only a modest increase in TBARS. In muscle, there were no changes in TAC, PC, or TBARS, regardless of exercise intensity, In the liver, TAC and TBARS increased significantly in both the SBLIE and SBHIE groups. This indicates that the oxidative stress biomarkers measured in the plasma immediately after a single bout of swimming exercise were generated primarily in the liver, not in muscle. PMID:23668757

  9. Muscle and liver protein synthesis in growing rats fed diets containing raw legumes as the main source of protein

    SciTech Connect

    Goena, M.; Santidrian, S.; Cuevillas, F.; Larralde, J.

    1986-03-01

    Although legumes are widely used as protein sources, their effects on protein metabolism remain quite unexplored. The authors have measured the rates of gastrocnemius muscle and liver protein synthesis in growing rats fed ad libitum over periods of 12 days on diets containing raw field bean (Vicia faba L.), raw kidney bean (Phaseolus vulgaris L.), and raw bitter vetch (Vicia ervilia L.) as the major sources of protein. Diets were isocaloric and contained about 12% protein. Protein synthesis was evaluated by the constant-intravenous-infusion method, using L-//sup 14/C/-tyrosine, as well as by the determination of the RNA-activity (g of newly synthesized protein/day/g RNA). Results showed that, as compared to well-fed control animals, those fed the raw legume diets exhibited a marked reduction in the rate of growth with no changes in the amount of food intake (per 100 g b.wt.). These changes were accompanied by a significant reduction in the rate of muscle protein synthesis in all legume-treated rats, being this reduction greater in the animals fed the Ph. vulgaris and V. ervilia diets. Liver protein synthesis was slightly higher in the rats fed the V. faba and V. ervilia diets, and smaller in the Ph. vulgaris-fed rats. It is suggested that both sulfur amino acid deficiency and the presence of different anti-nutritive factors in raw legumes may account for these effects.

  10. Motoneuronal and muscle synergies involved in cat hindlimb control during fictive and real locomotion: a comparison study.

    PubMed

    Markin, Sergey N; Lemay, Michel A; Prilutsky, Boris I; Rybak, Ilya A

    2012-04-01

    We compared the activity profiles and synergies of spinal motoneurons recorded during fictive locomotion evoked in immobilized decerebrate cat preparations by midbrain stimulation to the activity profiles and synergies of the corresponding hindlimb muscles obtained during forward level walking in cats. The fictive locomotion data were collected in the Spinal Cord Research Centre, University of Manitoba, and provided by Dr. David McCrea; the real locomotion data were obtained in the laboratories of M. A. Lemay and B. I. Prilutsky. Scatterplot representation and minimum spanning tree clustering algorithm were used to identify the possible motoneuronal and muscle synergies operating during both fictive and real locomotion. We found a close similarity between the activity profiles and synergies of motoneurons innervating one-joint muscles during fictive locomotion and the profiles and synergies of the corresponding muscles during real locomotion. However, the activity patterns of proximal nerves controlling two-joint muscles, such as posterior biceps and semitendinosus (PBSt) and rectus femoris (RF), were not uniform in fictive locomotion preparations and differed from the activity profiles of the corresponding two-joint muscles recorded during forward level walking. Moreover, the activity profiles of these nerves and the corresponding muscles were unique and could not be included in the synergies identified in fictive and real locomotion. We suggest that afferent feedback is involved in the regulation of locomotion via motoneuronal synergies controlled by the spinal central pattern generator (CPG) but may also directly affect the activity of motoneuronal pools serving two-joint muscles (e.g., PBSt and RF). These findings provide important insights into the organization of the spinal CPG in mammals, the motoneuronal and muscle synergies engaged during locomotion, and their afferent control. PMID:22190626

  11. Motoneuronal and muscle synergies involved in cat hindlimb control during fictive and real locomotion: a comparison study

    PubMed Central

    Markin, Sergey N.; Lemay, Michel A.; Prilutsky, Boris I.

    2012-01-01

    We compared the activity profiles and synergies of spinal motoneurons recorded during fictive locomotion evoked in immobilized decerebrate cat preparations by midbrain stimulation to the activity profiles and synergies of the corresponding hindlimb muscles obtained during forward level walking in cats. The fictive locomotion data were collected in the Spinal Cord Research Centre, University of Manitoba, and provided by Dr. David McCrea; the real locomotion data were obtained in the laboratories of M. A. Lemay and B. I. Prilutsky. Scatterplot representation and minimum spanning tree clustering algorithm were used to identify the possible motoneuronal and muscle synergies operating during both fictive and real locomotion. We found a close similarity between the activity profiles and synergies of motoneurons innervating one-joint muscles during fictive locomotion and the profiles and synergies of the corresponding muscles during real locomotion. However, the activity patterns of proximal nerves controlling two-joint muscles, such as posterior biceps and semitendinosus (PBSt) and rectus femoris (RF), were not uniform in fictive locomotion preparations and differed from the activity profiles of the corresponding two-joint muscles recorded during forward level walking. Moreover, the activity profiles of these nerves and the corresponding muscles were unique and could not be included in the synergies identified in fictive and real locomotion. We suggest that afferent feedback is involved in the regulation of locomotion via motoneuronal synergies controlled by the spinal central pattern generator (CPG) but may also directly affect the activity of motoneuronal pools serving two-joint muscles (e.g., PBSt and RF). These findings provide important insights into the organization of the spinal CPG in mammals, the motoneuronal and muscle synergies engaged during locomotion, and their afferent control. PMID:22190626

  12. Evidence for the involvement of the CXCL12 system in the adaptation of skeletal muscles to physical exercise.

    PubMed

    Puchert, Malte; Adams, Volker; Linke, Axel; Engele, Jürgen

    2016-09-01

    The chemokine CXCL12 and its primary receptor, CXCR4, not only promote developmental myogenesis, but also muscle regeneration. CXCL12 chemoattracts CXCR4-positive satellite cells/blood-borne progenitors to the injured muscle, promotes myoblast fusion, partially with existing myofibers, and induces angiogenesis in regenerating muscles. Interestingly, the mechanisms underlying muscle regeneration are in part identical to those involved in muscular adaptation to intensive physical exercise. These similarities now prompted us to determine whether physical exercise would impact the CXCL12 system in skeletal muscle. We found that CXCL12 and CXCR4 are upregulated in the gastrocnemius muscle of rats that underwent a four-week period of constrained daily running exercise on a treadmill. Double-staining experiments confirmed that CXCL12 and CXCR4 are predominantly expressed in MyHC-positive muscle fibers. Moreover, these training-dependent increases in CXCL12 and CXCR4 expression also occurred in rats with surgical coronary artery occlusion, implying that the muscular CXCL12 system is still active in skeletal myopathy resulting from chronic heart failure. Expression of the second CXCL12 receptor, CXCR7, which presumably acts as a scavenger receptor in muscle, was not affected by training. Attempts to dissect the molecular events underlying the training-dependent effects of CXCL12 revealed that the CXCL12-CXCR4 axis activates anabolic mTOR-p70S6K signaling and prevents upregulation of the catabolic ubiquitin ligase MurF-1 in C2C12 myotubes, eventually increasing myotube diameters. Together, these findings point to a pivotal role of the CXCL12-CXCR4 axis in exercise-induced muscle maintenance and/or growth. PMID:27237374

  13. Determination of endocrine disrupting compounds in fish liver, brain, and muscle using focused ultrasound solid-liquid extraction and dispersive solid phase extraction as clean-up strategy.

    PubMed

    Ros, Oihana; Vallejo, Asier; Olivares, Maitane; Etxebarria, Nestor; Prieto, Ailette

    2016-08-01

    This study describes a new method for the simultaneous extraction of several endocrine disrupting compounds, including alkylphenols (APs), estrogen, bisphenol-A (BPA) and one phthalate metabolite (mono-2-ethylhexyl ester, MEHP) in fish liver, brain, and muscle. Parameters affecting the extraction (extraction solvent and temperature) and the clean-up (dispersive phase nature and amount) steps were evaluated. The extraction was performed by means of focused ultrasound solid-liquid extraction (FUSLE) using 10 mL of n-hexane:acetone (50:50, v/v) for 5 min at ~0 °C, and the clean-up was done by means of dispersive solid phase extraction (dSPE) using 100 mg of ENVI-CARB and 100 mg of MgSO4 for the cleaning of brain and muscle extracts together with 100 mg of PSA in the case of liver extracts. Good apparent recoveries were obtained in the case of liver (62-132 %), brain (66-120 %), and muscle (74-129 %), relative standard deviation (RSD%) was always below 26 %, and the method detection limits (MDLs) were at low ng/g level. The developed method was applied to fish captured in Urdaibai estuary (Bay of Biscay) in December 2015, and the concentrations obtained were in the range MDL-1115 ng/g in brain, MDL-962 ng/g in muscle, and MDL-672 ng/g in liver. In general, the highest concentrations were measured in liver, followed by brain and muscle. In addition, diethylstilbestrol was only detected in fish brain. Graphical Abstract MS method scheme for the/MS method scheme for the determination of EDCs in fish liver, brain and muscle. PMID:27342793

  14. Variation in metabolic enzymatic activity in white muscle and liver of blue tilapia, Oreochromis aureus, in response to long-term thermal acclimatization

    NASA Astrophysics Data System (ADS)

    Younis, Elsayed M.

    2015-05-01

    The effects of rearing temperature on white muscle and hepatic phosphofructokinase (PFK), pyruvate kinase (PK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were examined in fingerlings of blue tilapia, Oreochromis aureus. The experiment was conducted for 14 weeks at temperatures of 18, 22, 26, 30, and 34°C. The activity of the glycolytic enzymes PFK, PK, and LDH in white muscle increased significantly with increase in water temperature. A reverse trend was observed for these enzymes in the liver, except for LDH, which behaved in the same manner as in white muscle. Cytosolic AST and ALT activity increased in both white muscle and liver in response to warm thermal acclimatization, while a reduction in mitochondrial AST and ALT activity was noticed at high temperatures in comparison with those at a lower temperature.

  15. Pterostilbene improves glycaemic control in rats fed an obesogenic diet: Involvement of skeletal muscle and liver

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study aimed to determine whether pterostilbene improved glycaemic control in rats showing insulin resistance induced by an obesogenic diet. Rats were divided into 3 groups: control group and two groups treated with either 15 mg/kg/d (PT15) or 30 mg/kg/d of pterostilbene (PT30). HOMA-IR was decr...

  16. Exercise Intensity Modulates Glucose-Stimulated Insulin Secretion when Adjusted for Adipose, Liver and Skeletal Muscle Insulin Resistance

    PubMed Central

    Malin, Steven K.; Rynders, Corey A.; Weltman, Judy Y.; Barrett, Eugene J.; Weltman, Arthur

    2016-01-01

    Little is known about the effects of exercise intensity on compensatory changes in glucose-stimulated insulin secretion (GSIS) when adjusted for adipose, liver and skeletal muscle insulin resistance (IR). Fifteen participants (8F, Age: 49.9±3.6yr; BMI: 31.0±1.5kg/m2; VO2peak: 23.2±1.2mg/kg/min) with prediabetes (ADA criteria, 75g OGTT and/or HbA1c) underwent a time-course matched Control, and isocaloric (200kcal) exercise at moderate (MIE; at lactate threshold (LT)), and high-intensity (HIE; 75% of difference between LT and VO2peak). A 75g OGTT was conducted 1 hour post-exercise/Control, and plasma glucose, insulin, C-peptide and free fatty acids were determined for calculations of skeletal muscle (1/Oral Minimal Model; SMIR), hepatic (HOMAIR), and adipose (ADIPOSEIR) IR. Insulin secretion rates were determined by deconvolution modeling for GSIS, and disposition index (DI; GSIS/IR; DISMIR, DIHOMAIR, DIADIPOSEIR) calculations. Compared to Control, exercise lowered SMIR independent of intensity (P<0.05), with HIE raising HOMAIR and ADIPOSEIR compared with Control (P<0.05). GSIS was not reduced following exercise, but DIHOMAIR and DIADIPOSEIR were lowered more following HIE compared with Control (P<0.05). However, DISMIR increased in an intensity based manner relative to Control (P<0.05), which corresponded with lower post-prandial blood glucose levels. Taken together, pancreatic insulin secretion adjusts in an exercise intensity dependent manner to match the level of insulin resistance in skeletal muscle, liver and adipose tissue. Further work is warranted to understand the mechanism by which exercise influences the cross-talk between tissues that regulate blood glucose in people with prediabetes. PMID:27111219

  17. The Involving Roles of Intrahepatic and Extrahepatic Stem/Progenitor Cells (SPCs) to Liver Regeneration

    PubMed Central

    Liu, Wei-hui; Ren, Li-na; Wang, Tao; Navarro-Alvarez, Nalu; Tang, Li-jun

    2016-01-01

    Liver regeneration is usually attributed to mature hepatocytes, which possess a remarkable potential to proliferate under mild to moderate injury. However, when the liver is severely damaged or hepatocyte proliferation is greatly inhibited, liver stem/progenitor cells (LSPCs) will contribute to the liver regeneration process. LSPCs in the developing liver have been extensively characterized, however, their contributing role to liver regeneration has not been completely understood. In addition to the restoration of the liver parenchymal tissue by hepatocytes or/and LSPCs, or in some cases bone marrow (BM) derived cells, such as hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs), the wound healing after injury in terms of angiopoiesis by liver sinusoidal endothelial cells (LSECs) or/and sinusoidal endothelial progenitor cells (SEPCs) is another important aspect taking place during regeneration. To conclude, liver regeneration can be mainly divided into three distinct restoring levels according to the cause and severity of injury: hepatocyte dominant regeneration, LSPCs mediated regeneration, extrahepatic stem cells participative regeneration. In this review, we focus on the recent findings of liver regeneration, especially on those related to stem/progenitor cells (SPCs)-mediated regeneration and their potential clinical applications and challenges. PMID:27489499

  18. Validation of Mitochondrial Gene Delivery in Liver and Skeletal Muscle via Hydrodynamic Injection Using an Artificial Mitochondrial Reporter DNA Vector.

    PubMed

    Yasuzaki, Yukari; Yamada, Yuma; Ishikawa, Takuya; Harashima, Hideyoshi

    2015-12-01

    For successful mitochondrial transgene expression, two independent processes, i.e., developing a mitochondrial gene delivery system and construction of DNA vector to achieve mitochondrial gene expression, are required. To date, very few studies dealing with mitochondrial gene delivery have been reported and, in most cases, transgene expression was not validated, because the construction of a reporter DNA vector for mitochondrial gene expression is the bottleneck. In this study, mitochondrial transgene expression by the in vivo mitochondrial gene delivery of an artificial mitochondrial reporter DNA vector via hydrodynamic injection is demonstrated. In the procedure, a large volume of naked plasmid DNA (pDNA) is rapidly injected. We designed and constructed pHSP-mtLuc (CGG) as a mitochondrial reporter DNA vector that possesses a mitochondrial heavy strand promoter (HSP) and an artificial mitochondrial genome with the reporter NanoLuc (Nluc) luciferase gene that records adjustments to the mitochondrial codon system. We delivered the pDNA into mouse liver mitochondria by hydrodynamic injection, and detected exogenous mRNA in the liver using reverse transcription PCR analysis. The hydrodynamic injection of pHSP-mtLuc (CGG) resulted in the expression of the Nluc luciferase protein in liver and skeletal muscle. Our mitochondrial transgene expression reporter system would contribute to mitochondrial gene therapy and further studies directed at mitochondrial molecular biology. PMID:26567847

  19. Liver.

    PubMed

    Kim, W R; Lake, J R; Smith, J M; Skeans, M A; Schladt, D P; Edwards, E B; Harper, A M; Wainright, J L; Snyder, J J; Israni, A K; Kasiske, B L

    2016-01-01

    The median waiting time for patients with MELD ≥ 35 decreased from 18 days in 2012 to 9 days in 2014, after implementation of the Share 35 policy in June 2013. Similarly, mortality among candidates listed with MELD ≥ 35 decreased from 366 per 100 waitlist years in 2012 to 315 in 2014. The number of new active candidates added to the pediatric liver transplant waiting list in 2014 was 655, down from a peak of 826 in 2005. The number of prevalent candidates (on the list on December 31 of the given year) continued to decline, 401 active and 173 inactive. The number of deceased donor pediatric liver transplants peaked at 542 in 2008 and was 478 in 2014. The number of living donor liver pediatric transplants was 52 in 2014; most were from donors closely related to the recipients. Graft survival continued to improve among pediatric recipients of deceased donor and living donor livers. PMID:26755264

  20. Transient elastography-derived liver stiffness measurements were found to be useful for predicting liver infiltration in a case of mature T-cell neoplasm involving liver dysfunction

    PubMed Central

    Ichikawa, Kunimoto; Narita, Yutaka; Ota, Yasunori; Komatsu, Norio; Koike, Michiaki

    2015-01-01

    Transient elastography (TE) is a novel, non-invasive imaging technique for measuring liver stiffness (LS). It is considered to be useful for predicting the severity of fibrosis and the risk of cirrhosis or hepatocellular carcinoma. However, the association between the presence of diffuse regions of increased cell density in the liver and elevated LS values has not been assessed. We experienced a case in which a mature T-cell neoplasm had invaded the liver, but the infiltrating lesion was not detected by contrast-enhanced computed tomography (CT) or fluorodeoxyglucose positron emission tomography/CT scans. Instead, the tumor’s presence was indicated by the change in the patient’s TE-derived LS values after chemotherapy. At diagnosis liver dysfunction was detected in a biochemical examination, and mean LS value was as high as 25.4 kPa [interquartile range (IQR): 0.3, success rate (SR):100%]. After chemotherapy, the patient’s mean LS value fell to 4.3 kPa (IQR: 0.8, SR:100%). A follow-up pathological investigation demonstrated that proliferating abnormal T-cells were no longer present in the patient’s liver. This is the first report to describe the use of LS data to support a diagnosis of liver infiltration by tumor cells exhibiting a portal and sinusoidal distribution pattern rather than a focal pattern. Elevated TE-derived LS values should lead to hepatic tumor infiltration being considered during initial examinations or a suspicion of recurrence during follow-up examination of lymphoma patients who achieve complete remission, even when radiological investigations do not detect abnormalities in the liver. PMID:26097615

  1. Genes involved in muscle lipid composition in 15 European Bos taurus breeds.

    PubMed

    Dunner, S; Sevane, N; Garcia, D; Levéziel, H; Williams, J L; Mangin, B; Valentini, A

    2013-08-01

    Consumers demand healthy and palatable meat, both factors being affected by fat composition. However, red meat has relatively high concentration of saturated fatty acids and low concentration of the beneficial polyunsaturated fatty acids. To select animals prone to produce particular fat types, it is necessary to identify the genes influencing muscle lipid composition. This paper describes an association study in which a large panel of candidate genes involved in adipogenesis, lipid metabolism and energy homoeostasis was tested for effects on fat composition in 15 European cattle breeds. Sixteen genes were found to have significant effects on different lipid traits, and among these, CFL1 and MYOZ1 were found to have large effects on the ratio of 18:2/18:3, CRI1 on the amount of neutral adrenic acid (22:4 n-6), MMP1 on docosahexaenoic acid (22:6 n-3) and conjugated linoleic acid, PLTP on the ratio of n-6:n-3 and IGF2R on flavour. Several genes - ALDH2, CHRNE, CRHR2, DGAT1, IGFBP3, NEB, SOCS2, SUSP1, TCF12 and FOXO1 - also were found to be associated with both lipid and organoleptic traits although with smaller effect. The results presented here help in understanding the genetic and biochemical background underlying variations in fatty acid composition and flavour in beef. PMID:23611291

  2. Embryonic brain extract induces collagen biosynthesis in cultured muscle cells: involvement in acetylcholine receptor aggregation.

    PubMed Central

    Kalcheim, C; Vogel, Z; Duksin, D

    1982-01-01

    The involvement of extracellular matrix components in induction of the aggregation of acetylcholine (AcCho) receptors by factor(s) present in embryonic brain extract was investigated. Embryonic brain extract induced a three-fold increase in the number of AcCho receptor aggregates on the surface of cultured myotubes and a 5- to 10-fold increase in the synthesis of procollagen, which was secreted into the medium and converted to collagen. Adult brain extract, embryonic serum, and embryonic liver extract were less active in stimulating both collagen synthesis and AcCho receptor aggregation. A physiological connection between the two processes is suggested, since the number of AcCho receptor aggregates could be reduced to control levels by treating brain extract-stimulated myotubes with purified bacterial collagenase. In addition, stimulation of collagen secretion by ascorbic acid (50 micrograms/ml) promoted a 1.6-fold increase in AcCho receptor aggregation. When ascorbic acid was added together with the brain extract, further increases in both collagen synthesis and AcCho receptor aggregation were observed. Images PMID:6285338

  3. Reactive oxygen species and calcium signals in skeletal muscle: A crosstalk involved in both normal signaling and disease.

    PubMed

    Espinosa, Alejandra; Henríquez-Olguín, Carlos; Jaimovich, Enrique

    2016-09-01

    Reactive Oxygen Species (ROS) have been profusely studied as agents of potential damage to living cells and they have been related to a number of pathological processes. Increasing evidence points to a more positive role of ROS in cell signaling and the detailed mechanism that regulates the precise amount of ROS needed for cell functioning without the deleterious effects of excess ROS still needs to be resolved in detail. In skeletal muscle the main source of ROS during normal functioning appears to be NADPH oxidase 2 (NOX2), which is activated by electrical stimuli (or exercise) through a cascade of events that include ATP release through pannexin1 channels. NOX2 is a protein complex that assembles in the T-tubule membrane before activation and ROS production by NOX2 appears to be important for muscle adaptation through gene expression and mitochondrial biogenesis as well as for improving glucose transport after insulin action. Excess ROS production (or diminished antioxidant defenses) plays a role in a number of pathological processes in skeletal muscle. Together with increased reactive nitrogen species, an increase in ROS appears to have a deleterious role in a model of Duchenne muscular dystrophy as well as muscle wasting in other diseases such as aging sarcopenia and cancer cachexia. In addition, ROS is involved in obesity and muscle insulin resistance, both of which are causally related to type 2 diabetes. A detailed description of the fine-tuning of ROS (including all sources of ROS) in skeletal muscle in health and disease will significantly contribute to our knowledge of both muscle adaptation and muscle related pathologies. PMID:26965208

  4. Temporal changes in the involvement of pyruvate dehydrogenase complex in muscle lactate accumulation during lipopolysaccharide infusion in rats

    PubMed Central

    Alamdari, N; Constantin-Teodosiu, D; Murton, A J; Gardiner, S M; Bennett, T; Layfield, R; Greenhaff, P L

    2008-01-01

    A characteristic manifestation of sepsis is muscle lactate accumulation. This study examined any putative (causative) association between pyruvate dehydrogenase complex (PDC) inhibition and lactate accumulation in the extensor digitorum longus (EDL) muscle of rats infused with lipopolysaccharide (LPS), and explored the involvement of increased transcription of muscle-specific pyruvate dehydrogenase kinase (PDK) isoenzymes. Conscious, male Sprague–Dawley rats were infused i.v. with saline (0.4 ml h−1, control) or LPS (150 μg kg−1 h−1) for 2 h, 6 h or 24 h (n = 6–8). Muscle lactate concentration was elevated after 2, 6 and 24 h LPS infusion. Muscle PDC activity was the same at 2 h and 6 h, but was 65% lower after 24 h of LPS infusion (P < 0.01), when there was a 47% decrease in acetylcarnitine concentration (P < 0.05), and a 24-fold increase in PDK4 mRNA expression (P < 0.001). These changes were preceded by marked increases in tumour necrosis factor-α and interleukin-6 mRNA expression at 2 h. The findings indicate that the early (2 and 6 h) elevation in muscle lactate concentration during LPS infusion was not attributable to limited muscle oxygen availability or ATP production (evidenced by unchanged ATP and phosphocreatine (PCr) concentrations) or to PDC inhibition, whereas after 24 h, muscle lactate accumulation appears to have resulted from PDC activation status limiting pyruvate flux, most probably due to cytokine-mediated up-regulation of PDK4 transcription. PMID:18218678

  5. Regulation of retinoid mediated cholesterol efflux involves liver X receptor activation in mouse macrophages.

    PubMed

    Manna, Pulak R; Sennoune, Souad R; Martinez-Zaguilan, Raul; Slominski, Andrzej T; Pruitt, Kevin

    2015-08-14

    Removal of cholesterol from macrophage-derived foam cells is a critical step to the prevention of atherosclerotic lesions. We have recently demonstrated the functional importance of retinoids in the regulation of the steroidogenic acute regulatory (StAR) protein that predominantly mediates the intramitochondrial transport of cholesterol in target tissues. In the present study, treatment of mouse macrophages with retinoids, particularly all-trans retinoic acid (atRA) and 9-cis RA, resulted in increases in cholesterol efflux to apolipoprotein AI (Apo-A1). Activation of the PKA pathway by a cAMP analog, (Bu)2cAMP, markedly augmented retinoid mediated cholesterol efflux. Macrophages overexpressing hormone-sensitive lipase increased the hydrolysis of cholesteryl esters and concomitantly enhanced the efficacy of retinoic acid receptor and liver X receptor (LXR) ligands on StAR and ATP-binding cassette transporter A1 (ABCA1) protein levels. RAs elevated StAR promoter activity in macrophages, and an increase in StAR levels augmented cholesterol efflux to Apo-A1, suggesting retinoid-mediated efflux of cholesterol involves enhanced oxysterol production. Further studies revealed that retinoids activate the LXR regulated genes, sterol receptor-element binding protein-1c and ABCA1. These findings provide insights into the regulatory events in which retinoid signaling effectively enhances macrophage cholesterol efflux and indicate that retinoid therapy may have important implications in limiting and/or regressing atherosclerotic cardiovascular disease. PMID:26119689

  6. Single Muscle Immobilization Decreases Single-Fibre Myosin Heavy Chain Polymorphism: Possible Involvement of p38 and JNK MAP Kinases

    PubMed Central

    Derbré, Frédéric; Droguet, Mickaël; Léon, Karelle; Troadec, Samuel; Pennec, Jean-Pierre; Giroux-Metges, Marie-Agnès; Rannou, Fabrice

    2016-01-01

    Purpose Muscle contractile phenotype is affected during immobilization. Myosin heavy chain (MHC) isoforms are the major determinant of the muscle contractile phenotype. We therefore sought to evaluate the effects of muscle immobilization on both the MHC composition at single-fibre level and the mitogen-activated protein kinases (MAPK), a family of intracellular signaling pathways involved in the stress-induced muscle plasticity. Methods The distal tendon of female Wistar rat Peroneus Longus (PL) was cut and fixed to the adjacent bone at neutral muscle length. Four weeks after the surgery, immobilized and contralateral PL were dissociated and the isolated fibres were sampled to determine MHC composition. Protein kinase 38 (p38), extracellular signal-regulated kinases (ERK1/2), and c-Jun- NH2-terminal kinase (JNK) phosphorylations were measured in 6- and 15-day immobilized and contralateral PL. Results MHC distribution in immobilized PL was as follows: I = 0%, IIa = 11.8 ± 2.8%, IIx = 53.0 ± 6.1%, IIb = 35.3 ± 7.3% and I = 6.1 ± 3.9%, IIa = 22.1 ± 3.4%, IIx = 46.6 ± 4.5%, IIb = 25.2 ± 6.6% in contralateral muscle. The MHC composition in immobilized muscle is consistent with a faster contractile phenotype according to the Hill’s model of the force-velocity relationship. Immobilized and contralateral muscles displayed a polymorphism index of 31.1% (95% CI 26.1–36.0) and 39.3% (95% CI 37.0–41.5), respectively. Significant increases in p38 and JNK phosphorylation were observed following 6 and 15 days of immobilization. Conclusions Single muscle immobilization at neutral length induces a shift of MHC composition toward a faster contractile phenotype and decreases the polymorphic profile of single fibres. Activation of p38 and JNK could be a potential mechanism involved in these contractile phenotype modifications during muscle immobilization. PMID:27383612

  7. Mitochondrial involvement in skeletal muscle insulin resistance: A case of imbalanced bioenergetics.

    PubMed

    Affourtit, Charles

    2016-10-01

    Skeletal muscle insulin resistance in obesity associates with mitochondrial dysfunction, but the causality of this association is controversial. This review evaluates mitochondrial models of nutrient-induced muscle insulin resistance. It transpires that all models predict that insulin resistance arises as a result of imbalanced cellular bioenergetics. The nature and precise origin of the proposed insulin-numbing molecules differ between models but all species only accumulate when metabolic fuel supply outweighs energy demand. This observation suggests that mitochondrial deficiency in muscle insulin resistance is not merely owing to intrinsic functional defects, but could instead be an adaptation to nutrient-induced changes in energy expenditure. Such adaptive effects are likely because muscle ATP supply is fully driven by energy demand. This market-economic control of myocellular bioenergetics offers a mechanism by which insulin-signalling deficiency can cause apparent mitochondrial dysfunction, as insulin resistance lowers skeletal muscle anabolism and thus dampens ATP demand and, consequently, oxidative ATP synthesis. PMID:27473535

  8. A Cell Surface Molecule Involved in Aggregation of Embryonic Liver Cells

    NASA Astrophysics Data System (ADS)

    Bertolotti, Roger; Rutishauser, Urs; Edelman, Gerald M.

    1980-08-01

    Aggregation of chicken embryo hepatocytes can be inhibited by Fab' fragments of antibodies prepared against the cells. An aqueous extract of liver cell membranes contained antigens that neutralized the adhesion-blocking properties of the Fab' fragments. This neutralization activity was associated with a polypeptide of Mr 68,000 in NaDodSO4; the polypeptide was distinct from serum albumin. Specific antibodies prepared against the 80-fold purified active fraction inhibited liver cell adhesion and immunoprecipitated the 68,000 Mr polypeptide from active fractions as well as from a detergent extract of liver cell membranes. In hepatocyte cultures, Fab' fragments of antibodies against the liver molecule prevented both colony formation and appearance of histotypic patterns. Liver cell adhesion was compared at the cellular and molecular levels to that of embryonic neural retina cells. Antibodies against the cell adhesion molecule from neural tissue inhibited retinal but not liver cell aggregation; conversely, antibodies against the liver polypeptide inhibited liver but not retinal cell aggregation. By means of antibody absorption and immunoprecipitation, it was confirmed that the two cell adhesion molecules are antigenically unrelated.

  9. DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells

    SciTech Connect

    Obara, Akio; Fujita, Yoshihito; Abudukadier, Abulizi; Fukushima, Toru; Oguri, Yasuo; Ogura, Masahito; Harashima, Shin-ichi; Hosokawa, Masaya; Inagaki, Nobuya

    2015-05-15

    Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin's anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy. - Highlights: • We elucidated a novel pathway of metformin's anti-cancer action in HCC cells. • DEPTOR is involved in the suppressing effect of metformin on mTOR signaling. • Metformin increases DEPTOR protein levels via suppression of proteasome activity. • DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action.

  10. Vascular smooth muscle cell differentiation to an osteogenic phenotype involves matrix metalloproteinase-2 modulation by homocysteine.

    PubMed

    Liu, Tingjiao; Lin, Jinghan; Ju, Ting; Chu, Lei; Zhang, Liming

    2015-08-01

    Arterial calcification is common in vascular diseases and involves conversion of vascular smooth muscle cells (VSMCs) to an osteoblast phenotype. Clinical studies suggest that the development of atherosclerosis can be promoted by homocysteine (HCY), but the mechanisms remain unclear. Here, we determined whether increases in HCY levels lead to an increase in VSMC calcification and differentiation, and examined the role of an extracellular matrix remodeler, matrix metalloproteinase-2 (MMP-2). Rat VSMCs were exposed to calcification medium in the absence or presence of HCY (10, 100 or 200 μmol/L) or an MMP-2 inhibitor (10(-6) or 10(-5) mol/L). MTT assays were performed to determine the cytotoxicity of the MMP-2 inhibitor in calcification medium containing 200 μmol/L HCY. Calcification was assessed by measurements of calcium deposition and alkaline phosphatase (ALP) activity as well as von Kossa staining. Expression of osteocalcin, bone morphogenetic protein (BMP)-2, and osteopontin, and MMP-2 was determined by immunoblotting. Calcification medium induced osteogenic differentiation of VSMCs. HCY promoted calcification, increased osteocalcin and BMP-2 expression, and decreased expression of osteopontin. MMP-2 expression was increased by HCY in a dose-dependent manner in VSMCs exposed to both control and calcification medium. The MMP-2 inhibitor decreased the calcium content and ALP activity, and attenuated the osteoblastic phenotype of VSMCs. Vascular calcification and osteogenic differentiation of VSMCs were positively regulated by HCY through increased/restored MMP-2 expression, increased expression of calcification proteins, and decreased anti-calcification protein levels. In summary, MMP-2 inhibition may be a protective strategy against VSMC calcification. PMID:25987498

  11. Involvement of catecholaminergic neurons in motor innervation of striated muscle in the mouse esophagus.

    PubMed

    van der Keylen, Piet; Garreis, Fabian; Steigleder, Ruth; Sommer, Daniel; Neuhuber, Winfried L; Wörl, Jürgen

    2016-05-01

    Enteric co-innervation is a peculiar innervation pattern of striated esophageal musculature. Both anatomical and functional data on enteric co-innervation related to various transmitters have been collected in different species, although its function remains enigmatic. However, it is unclear whether catecholaminergic components are involved in such a co-innervation. Thus, we examined to identify catecholaminergic neuronal elements and clarify their relationship to other innervation components in the esophagus, using immunohistochemistry with antibodies against tyrosine hydroxylase (TH), vesicular acetylcholine transporter (VAChT), choline acetyltransferase (ChAT) and protein gene product 9.5 (PGP 9.5), α-bungarotoxin (α-BT) and PCR with primers for amplification of cDNA encoding TH and dopamine-β-hydroxylase (DBH). TH-positive nerve fibers were abundant throughout the myenteric plexus and localized on about 14% of α-BT-labelled motor endplates differing from VAChT-positive vagal nerve terminals. TH-positive perikarya represented a subpopulation of only about 2.8% of all PGP 9.5-positive myenteric neurons. Analysis of mRNA showed both TH and DBH transcripts in the mouse esophagus. As ChAT-positive neurons in the compact formation of the nucleus ambiguus were negative for TH, the TH-positive nerve varicosities on motor endplates are presumably of enteric origin, although a sympathetic origin cannot be excluded. In the medulla oblongata, the cholinergic ambiguus neurons were densely supplied with TH-positive varicosities. Thus, catecholamines may modulate vagal motor innervation of esophageal-striated muscles not only at the peripheral level via enteric co-innervation but also at the central level via projections to the nucleus ambiguus. As Parkinson's disease, with a loss of central dopaminergic neurons, also affects the enteric nervous system and dysphagia is prevalent in patients with this disease, investigation of intrinsic catecholamines in the esophagus may

  12. Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

    SciTech Connect

    Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao; Martyn, J.A. Jeevendra

    2013-02-01

    Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [{sup 3}H]glucose and 2-deoxy[{sup 14}C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats.

  13. Systematic Review and Meta-Analysis of the Impact of Computed Tomography-Assessed Skeletal Muscle Mass on Outcome in Patients Awaiting or Undergoing Liver Transplantation.

    PubMed

    van Vugt, J L A; Levolger, S; de Bruin, R W F; van Rosmalen, J; Metselaar, H J; IJzermans, J N M

    2016-08-01

    Liver transplant outcome has improved considerably as a direct result of optimized surgical and anesthesiological techniques and organ allocation programs. Because there remains a shortage of human organs, strict selection of transplant candidates remains of paramount importance. Recently, computed tomography (CT)-assessed low skeletal muscle mass (i.e. sarcopenia) was identified as a novel prognostic parameter to predict outcome in liver transplant candidates. A systematic review and meta-analysis on the impact of CT-assessed skeletal muscle mass on outcome in liver transplant candidates were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Nineteen studies, including 3803 patients in partly overlapping cohorts, fulfilled the inclusion criteria. The prevalence of sarcopenia ranged from 22.2% to 70%. An independent association between low muscle mass and posttransplantation and waiting list mortality was described in 4 of the 6 and 6 of the 11 studies, respectively. The pooled hazard ratios of sarcopenia were 1.84 (95% confidence interval 1.11-3.05, p = 0.02) and 1.72 (95% confidence interval 0.99-3.00, p = 0.05) for posttransplantation and waiting list mortality, respectively, independent of Model for End-stage Liver Disease score. Less-consistent evidence suggested a higher complication rate, particularly infections, in sarcopenic patients. In conclusion, sarcopenia is an independent predictor for outcome in liver transplantation patients and could be used for risk assessment. PMID:26813115

  14. Cloning and expression of the liver and muscle isoforms of ovine carnitine palmitoyltransferase 1: residues within the N-terminus of the muscle isoform influence the kinetic properties of the enzyme.

    PubMed Central

    Price, Nigel T; Jackson, Vicky N; van der Leij, Feike R; Cameron, Jacqueline M; Travers, Maureen T; Bartelds, Beatrijs; Huijkman, Nicolette C; Zammit, Victor A

    2003-01-01

    The nucleotide sequence data reported will appear in DDBJ, EMBL, GenBank(R) and GSDB Nucleotide Sequence Databases; the sequences of ovine CPT1A and CPT1B cDNAs have the accession numbers Y18387 and AJ272435 respectively and the partial adipose tissue and liver CPT1A clones have the accession numbers Y18830 and Y18829 respectively. Fatty acid and ketone body metabolism differ considerably between monogastric and ruminant species. The regulation of the key enzymes involved may differ accordingly. Carnitine palmitoyltransferase 1 (CPT 1) is the key locus for the control of long-chain fatty acid beta-oxidation and liver ketogenesis. Previously we showed that CPT 1 kinetics in sheep and rat liver mitochondria differ. We cloned cDNAs for both isoforms [liver- (L-) and muscle- (M-)] of ovine CPT 1 in order to elucidate the structural features of these proteins and their genes ( CPT1A and CPT1B ). Their deduced amino acid sequences show a high degree of conservation compared with orthologues from other mammalian species, with the notable exception of the N-terminus of ovine M-CPT 1. These differences were also present in bovine M-CPT 1, whose N-terminal sequence we determined. In addition, the 5'-end of the sheep CPT1B cDNA suggested a different promoter architecture when compared with previously characterized CPT1B genes. Northern blotting revealed differences in tissue distribution for both CPT1A and CPT1B transcripts compared with other species. In particular, ovine CPT1B mRNA was less tissue restricted, and the predominant transcript in the pancreas was CPT1B. Expression in yeast allowed kinetic characterization of the two native enzymes, and of a chimaera in which the distinctive N-terminal segment of ovine M-CPT 1 was replaced with that from rat M-CPT 1. The ovine N-terminal segment influences the kinetics of the enzyme for both its substrates, such that the K (m) for palmitoyl-CoA is decreased and that for carnitine is increased for the chimaera, relative to the

  15. Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

    PubMed Central

    Croft, Ashley M; Herxheimer, Andrew

    2002-01-01

    Background Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. Presentation We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs) may be related to the development of severe or prolonged adverse reactions to mefloquine. Implications We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. Testing Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis. PMID:11914150

  16. Effect of acetic acid feeding on the circadian changes in glycogen and metabolites of glucose and lipid in liver and skeletal muscle of rats.

    PubMed

    Fushimi, Takashi; Sato, Yuzo

    2005-11-01

    The aim of the present study is to investigate the effect of acetic acid feeding on the circadian changes in glycogen concentration in liver and skeletal muscle. Rats were provided meal once daily (09.00-13.00 hours) for 10 d. On the 11th day, they were either killed immediately or given 9 g diet containing either 0 (control) or 0.7 g/kg-diet acetic acid beginning at 09.00 hours for 4 h, as in the previous regimen. Rats in the fed group were killed at 4, 8 or 24 h after the start of feeding. At 4 h after the start of feeding, the acetic acid group had significantly greater liver and gastrocnemius muscle glycogen concentrations (P<0.05). Also, at this same point, liver xylulose-5-phosphate, a key stimulator of glycolysis, the ratio of fructose-1,6-bisphosphate to fructose-6-phosphate in skeletal muscle, which reflects phosphofructokinase-1 activity, and liver malonyl-CoA, an allosteric inhibitor of carnitine palmitoyl-transferase, were significantly lower in the acetic acid group than in the control group (P<0.05). In addition, the acetic acid group had a significantly lower serum lactate concentration and lower ratio of insulin to glucagon than the control group at the same point (P<0.05). We conclude that a diet containing acetic acid may enhance glycogen repletion but not induce supercompensation, a large increase in the glycogen level that is beneficial in improving performance, in liver and skeletal muscle by transitory inhibition of glycolysis. Further, we indicate the possibility of a transient enhancement of fatty acid oxidation in liver by acetic acid feeding. PMID:16277773

  17. Ingestion of glucose or sucrose prevents liver but not muscle glycogen depletion during prolonged endurance-type exercise in trained cyclists.

    PubMed

    Gonzalez, Javier T; Fuchs, Cas J; Smith, Fiona E; Thelwall, Pete E; Taylor, Roy; Stevenson, Emma J; Trenell, Michael I; Cermak, Naomi M; van Loon, Luc J C

    2015-12-15

    The purpose of this study was to define the effect of glucose ingestion compared with sucrose ingestion on liver and muscle glycogen depletion during prolonged endurance-type exercise. Fourteen cyclists completed two 3-h bouts of cycling at 50% of peak power output while ingesting either glucose or sucrose at a rate of 1.7 g/min (102 g/h). Four cyclists performed an additional third test for reference in which only water was consumed. We employed (13)C magnetic resonance spectroscopy to determine liver and muscle glycogen concentrations before and after exercise. Expired breath was sampled during exercise to estimate whole body substrate use. After glucose and sucrose ingestion, liver glycogen levels did not show a significant decline after exercise (from 325 ± 168 to 345 ± 205 and 321 ± 177 to 348 ± 170 mmol/l, respectively; P > 0.05), with no differences between treatments. Muscle glycogen concentrations declined (from 101 ± 49 to 60 ± 34 and 114 ± 48 to 67 ± 34 mmol/l, respectively; P < 0.05), with no differences between treatments. Whole body carbohydrate utilization was greater with sucrose (2.03 ± 0.43 g/min) vs. glucose (1.66 ± 0.36 g/min; P < 0.05) ingestion. Both liver (from 454 ± 33 to 283 ± 82 mmol/l; P < 0.05) and muscle (from 111 ± 46 to 67 ± 31 mmol/l; P < 0.01) glycogen concentrations declined during exercise when only water was ingested. Both glucose and sucrose ingestion prevent liver glycogen depletion during prolonged endurance-type exercise. Sucrose ingestion does not preserve liver glycogen concentrations more than glucose ingestion. However, sucrose ingestion does increase whole body carbohydrate utilization compared with glucose ingestion. This trial was registered at https://www.clinicaltrials.gov as NCT02110836. PMID:26487008

  18. Severe muscle depletion in patients on the liver transplant wait list: its prevalence and independent prognostic value.

    PubMed

    Tandon, Puneeta; Ney, Michael; Irwin, Ivana; Ma, Mang M; Gramlich, Leah; Bain, Vincent G; Esfandiari, Nina; Baracos, Vickie; Montano-Loza, Aldo J; Myers, Robert P

    2012-10-01

    As detected by cross-sectional imaging, severe muscle depletion, which is termed sarcopenia, holds promise for prognostication in patients with cirrhosis. Our aims were to describe the prevalence and predictors of sarcopenia in patients with cirrhosis listed for liver transplantation (LT) and to determine its independent prognostic significance for the prediction of waiting-list mortality. Adults listed for LT who underwent abdominal computed tomography/magnetic resonance imaging within 6 weeks of activation were retrospectively identified. The exclusions were hepatocellular carcinoma, acute liver failure, prior LT, and listing for multivisceral transplantation or living related LT. Sixty percent of the 142 eligible patients were male, the median age was 53 years, and the median Model for End-Stage Liver Disease (MELD) score at listing was 15. Forty-one percent were sarcopenic; sarcopenia was more prevalent in males versus females (54% versus 21%, P < 0.001) and increased with the Child-Pugh class (10% for class A, 34% for class B, and 54% for class C, P = 0.007). Male sex, the dry-weight body mass index (BMI), and Child-Pugh class C cirrhosis (but not the MELD score) were independent predictors of sarcopenia. Sarcopenia was an independent predictor of mortality (hazard ratio = 2.36, 95% confidence interval = 1.23-4.53) after adjustments for age and MELD scores. In conclusion, sarcopenia is associated with increased waiting-list mortality and is poorly predicted by subjective nutritional assessment tools such as BMI and subjective global assessment. If this is validated in larger studies, the objective assessment of sarcopenia holds promise for prognostication in this patient population. PMID:22740290

  19. T-to-R switch of muscle fructose-1,6-bisphosphatase involves fundamental changes of secondary and quaternary structure.

    PubMed

    Barciszewski, Jakub; Wisniewski, Janusz; Kolodziejczyk, Robert; Jaskolski, Mariusz; Rakus, Dariusz; Dzugaj, Andrzej

    2016-04-01

    Fructose-1,6-bisphosphatase (FBPase) catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and is a key enzyme of gluconeogenesis and glyconeogenesis and, more generally, of the control of energy metabolism and glucose homeostasis. Vertebrates, and notably Homo sapiens, express two FBPase isoforms. The liver isozyme is expressed mainly in gluconeogenic organs, where it functions as a regulator of glucose synthesis. The muscle isoform is expressed in all cells, and recent studies have demonstrated that its role goes far beyond the enzymatic function, as it can interact with various nuclear and mitochondrial proteins. Even in its enzymatic function, the muscle enzyme is different from the liver isoform, as it is 100-fold more susceptible to allosteric inhibition by AMP and this effect can be abrogated by complex formation with aldolase. All FBPases are homotetramers composed of two intimate dimers: the upper dimer and the lower dimer. They oscillate between two conformational states: the inactive T form when in complex with AMP, and the active R form. Parenthetically, it is noted that bacterial FBPases behave somewhat differently, and in the absence of allosteric activators exist in a tetramer-dimer equilibrium even at relatively high concentrations. [Hines et al. (2007), J. Biol. Chem. 282, 11696-11704]. The T-to-R transition is correlated with the conformation of the key loop L2, which in the T form becomes `disengaged' and unable to participate in the catalytic mechanism. The T states of both isoforms are very similar, with a small twist of the upper dimer relative to the lower dimer. It is shown that at variance with the well studied R form of the liver enzyme, which is flat, the R form of the muscle enzyme is diametrically different, with a perpendicular orientation of the upper and lower dimers. The crystal structure of the muscle-isozyme R form shows that in this arrangement of the tetramer completely new protein surfaces are exposed

  20. T-to-R switch of muscle fructose-1,6-bisphosphatase involves fundamental changes of secondary and quaternary structure

    PubMed Central

    Barciszewski, Jakub; Wisniewski, Janusz; Kolodziejczyk, Robert; Jaskolski, Mariusz; Rakus, Dariusz; Dzugaj, Andrzej

    2016-01-01

    Fructose-1,6-bisphosphatase (FBPase) catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and is a key enzyme of gluconeogenesis and glyconeogenesis and, more generally, of the control of energy metabolism and glucose homeostasis. Vertebrates, and notably Homo sapiens, express two FBPase isoforms. The liver isozyme is expressed mainly in gluconeogenic organs, where it functions as a regulator of glucose synthesis. The muscle isoform is expressed in all cells, and recent studies have demonstrated that its role goes far beyond the enzymatic function, as it can interact with various nuclear and mitochondrial proteins. Even in its enzymatic function, the muscle enzyme is different from the liver isoform, as it is 100-fold more susceptible to allosteric inhibition by AMP and this effect can be abrogated by complex formation with aldolase. All FBPases are homotetramers composed of two intimate dimers: the upper dimer and the lower dimer. They oscillate between two conformational states: the inactive T form when in complex with AMP, and the active R form. Parenthetically, it is noted that bacterial FBPases behave somewhat differently, and in the absence of allosteric activators exist in a tetramer–dimer equilibrium even at relatively high concentrations. [Hines et al. (2007 ▸), J. Biol. Chem. 282, 11696–11704]. The T-to-R transition is correlated with the conformation of the key loop L2, which in the T form becomes ‘disengaged’ and unable to participate in the catalytic mechanism. The T states of both isoforms are very similar, with a small twist of the upper dimer relative to the lower dimer. It is shown that at variance with the well studied R form of the liver enzyme, which is flat, the R form of the muscle enzyme is diametrically different, with a perpendicular orientation of the upper and lower dimers. The crystal structure of the muscle-isozyme R form shows that in this arrangement of the tetramer completely new protein surfaces

  1. Variations in genes involved in immune response checkpoints and association with outcomes in patients with resected colorectal liver metastases.

    PubMed

    Stremitzer, S; Sunakawa, Y; Zhang, W; Yang, D; Ning, Y; Stintzing, S; Sebio, A; Yamauchi, S; Matsusaka, S; El-Khoueiry, R; Stift, J; Wrba, F; Gruenberger, T; Lenz, H-J

    2015-12-01

    In patients with colorectal liver metastases (CLM), liver resection offers the possibility of cure and long-term survival. The liver is a highly immunogenic organ harboring ~80% of the body's tissue macrophages. Emerging data demonstrate a critical role of the immune response for cancer treatment. We investigated variations within genes involved in immune response checkpoints and their association with outcomes in patients with CLM who underwent neoadjuvant chemotherapy including bevacizumab and liver resection. Single-nucleotide polymorphisms (SNPs) in nine genes (CCL2, CCR2, LAG3, NT5E, PDCD1, CD274, IDO1, CTLA4 and CD24) were analyzed in genomic DNA from 149 patients with resected bevacizumab-pretreated CLM by direct Sanger DNA sequencing, and correlated with response, recurrence-free survival (RFS), overall survival (OS), probability of cure and recurrence patterns. IDO1 (indoleamine 2, 3-dioxygenase) rs3739319 G>A and CD24 rs8734 G>A showed a significant difference in 3-year OS rates. In addition, IDO1 rs3739319 G>A was significantly associated with extrahepatic recurrence. Recursive partitioning analyses revealed that IDO1 rs3739319 G>A was the dominant SNP predicting RFS and OS. Our data suggest that variants within genes involved in immune response checkpoints are associated with outcomes in patients with resected CLM and might lead to improved treatment strategies modulating anti-tumor immune response by targeting novel immune checkpoints. PMID:25752522

  2. Heat-shock responsive genes identified and validated in Atlantic cod (Gadus morhua) liver, head kidney and skeletal muscle using genomic techniques

    PubMed Central

    2010-01-01

    Background Daily and seasonal changes in temperature are challenges that fish within aquaculture settings cannot completely avoid, and are known to elicit complex organismal and cellular stress responses. We conducted a large-scale gene discovery and transcript expression study in order to better understand the genes that are potentially involved in the physiological and cellular aspects of stress caused by heat-shock. We used suppression subtractive hybridization (SSH) cDNA library construction and characterization to identify transcripts that were dysregulated by heat-shock in liver, skeletal muscle and head kidney of Atlantic cod. These tissues were selected due to their roles in metabolic regulation, locomotion and growth, and immune function, respectively. Fish were exposed for 3 hours to an 8°C elevation in temperature, and then allowed to recover for 24 hours at the original temperature (i.e. 10°C). Tissue samples obtained before heat-shock (BHS), at the cessation of heat-shock (CS), and 3, 12, and 24 hours after the cessation of heat-shock (ACS), were used for reciprocal SSH library construction and quantitative reverse transcription - polymerase chain reaction (QPCR) analysis of gene expression using samples from a group that was transferred but not heat-shocked (CT) as controls. Results We sequenced and characterized 4394 ESTs (1524 from liver, 1451 from head kidney and 1419 from skeletal muscle) from three "forward subtracted" libraries (enriched for genes up-regulated by heat-shock) and 1586 from the liver "reverse subtracted" library (enriched for genes down-regulated by heat-shock), for a total of 5980 ESTs. Several cDNAs encoding putative chaperones belonging to the heat-shock protein (HSP) family were found in these libraries, and "protein folding" was among the gene ontology (GO) terms with the highest proportion in the libraries. QPCR analysis of HSP90α and HSP70-1 (synonym: HSPA1A) mRNA expression showed significant up-regulation in all three

  3. Involvement of Mouse Constitutive Androstane Receptor in Acifluorfen-Induced Liver Injury and Subsequent Tumor Development.

    PubMed

    Kuwata, Kazunori; Inoue, Kaoru; Ichimura, Ryohei; Takahashi, Miwa; Kodama, Yukio; Shibutani, Makoto; Yoshida, Midori

    2016-06-01

    Acifluorfen (ACI), a protoporphyrinogen oxidase (PROTOX) inhibitor herbicide, promotes the accumulation of protoporphyrin IX (PPIX), and induces tumors in the rodent liver. Porphyria is a risk factor for liver tumors in humans; however, the specific mechanisms through which ACI induces hepatocarcinogenesis in rodents are unclear. Here, we investigated the mode of action of ACI-induced hepatocarcinogenesis, focusing on constitutive androstane receptor (CAR, NR1I3), which is essential for the development of rodent liver tumors in response to certain cytochrome P450 (CYP) 2B inducers. Dietary treatment with 2500 ppm ACI for up to 13 weeks increased Cyp2b10 expression in the livers of wild-type (WT) mice, but not in CAR-knockout (CARKO) mice. Microscopically, ACI treatment-induced cytotoxic changes, including hepatocellular necrosis and inflammation, and caused regenerative changes accompanied by prolonged increases in the numbers of proliferating cell nuclear antigen-positive hepatocytes in WT mice. In contrast, these cytotoxic and regenerative changes in hepatocytes were significantly attenuated, but still observed, in CARKO mice. ACI treatment also increased liver PPIX levels similarly in both genotypes; however, no morphological evidence of porphyrin deposition was found in hepatocytes from either genotype. Treatment with 2500 ppm ACI for 26 weeks after initiation with diethylnitrosamine increased the incidence and multiplicities of altered foci and adenomas in hepatocytes from WT mice; these effects were significantly reduced in CARKO mice. These results indicated that prolonged cytotoxicity in the liver was a key factor for ACI-induced hepatocarcinogenesis, and that CAR played an important role in ACI-induced liver injury and tumor development in mice. PMID:26928356

  4. Involvement of mTOR in Type 2 CRF Receptor Inhibition of Insulin Signaling in Muscle Cells.

    PubMed

    Chao, Hongxia; Li, Haochen; Grande, Rebecca; Lira, Vitor; Yan, Zhen; Harris, Thurl E; Li, Chien

    2015-06-01

    Type 2 corticotropin-releasing factor receptor (CRFR2) is expressed in skeletal muscle and stimulation of the receptor has been shown to inhibit the effect of insulin on glucose uptake in muscle cells. Currently, little is known about the mechanisms underlying this process. In this study, we first showed that both in vivo and in vitro CRFR2 expression in muscle was closely correlated with insulin sensitivity, with elevated receptor levels observed in insulin resistant muscle cells. Stimulation of CRFR2 by urocortin 2 (Ucn 2), a CRFR2-selective ligand, in C2C12 myotubes greatly attenuated insulin-induced glucose uptake. The inhibitory effect of CRFR2 signaling required cAMP production and is involved the mammalian target of rapamycine pathway, as rapamycin reversed the inhibitory effect of CRFR2 stimulation on insulin-induced glucose uptake. Moreover, stimulation of CRFR2 failed to inhibit glucose uptake in muscle cells induced by platelet-derived growth factor, which, similar to insulin, signals through Akt-mediated pathway but is independently of insulin receptor substrate (IRS) proteins to promote glucose uptake. This result argues that CRFR2 signaling modulates insulin's action likely at the levels of IRS. Consistent with this notion, Ucn 2 reduced insulin-induced tyrosine phosphorylation of IRS-1, and treatment with rapamycin reversed the inhibitory effect of Ucn 2 on IRS-1 and Akt phosphorylation. In conclusion, the inhibitory effect of CRFR2 signaling on insulin action is mediated by cAMP in a mammalian target of rapamycine-dependent manner, and IRS-1 is a key nodal point where CRFR2 signaling modulates insulin-stimulated glucose uptake in muscle cells. PMID:25875045

  5. Involvement of AMPK in regulating slow-twitch muscle atrophy during hindlimb unloading in mice.

    PubMed

    Egawa, Tatsuro; Goto, Ayumi; Ohno, Yoshitaka; Yokoyama, Shingo; Ikuta, Akihiro; Suzuki, Miho; Sugiura, Takao; Ohira, Yoshinobu; Yoshioka, Toshitada; Hayashi, Tatsuya; Goto, Katsumasa

    2015-10-01

    AMPK is considered to have a role in regulating skeletal muscle mass. However, there are no studies investigating the function of AMPK in modulating skeletal muscle mass during atrophic conditions. In the present study, we investigated the difference in unloading-associated muscle atrophy and molecular functions in response to 2-wk hindlimb suspension between transgenic mice overexpressing the dominant-negative mutant of AMPK (AMPK-DN) and their wild-type (WT) littermates. Male WT (n = 24) and AMPK-DN (n = 24) mice were randomly divided into two groups: an untreated preexperimental control group (n = 12 in each group) and an unloading (n = 12 in each group) group. The relative soleus muscle weight and fiber cross-sectional area to body weight were decreased by ∼30% in WT mice by hindlimb unloading and by ∼20% in AMPK-DN mice. There were no changes in puromycin-labeled protein or Akt/70-kDa ribosomal S6 kinase signaling, the indicators of protein synthesis. The expressions of ubiquitinated proteins and muscle RING finger 1 mRNA and protein, markers of the ubiquitin-proteasome system, were increased by hindlimb unloading in WT mice but not in AMPK-DN mice. The expressions of molecules related to the protein degradation system, phosphorylated forkhead box class O3a, inhibitor of κBα, microRNA (miR)-1, and miR-23a, were decreased only in WT mice in response to hindlimb unloading, and 72-kDa heat shock protein expression was higher in AMPK-DN mice than in WT mice. These results imply that AMPK partially regulates unloading-induced atrophy of slow-twitch muscle possibly through modulation of the protein degradation system, especially the ubiquitin-proteasome system. PMID:26244519

  6. Identification of Annexin A4 as a hepatopancreas factor involved in liver cell survival

    PubMed Central

    Zhang, Danhua; Golubkov, Vladislav S.; Han, Wenlong; Correa, Ricardo G.; Zhou, Ying; Lee, Sunyoung; Strongin, Alex Y.; Dong, P. Duc Si

    2014-01-01

    To gain insight into liver and pancreas development, we investigated the target of 2F11, a monoclonal antibody of unknown antigen, widely used in zebrafish studies for labeling hepatopancreatic ducts. Utilizing mass spectrometry and in vivo assays, we determined the molecular target of 2F11 to be Annexin A4 (Anxa4), a calcium binding protein. We further found that in both zebrafish and mouse endoderm, Anxa4 is broadly expressed in the developing liver and pancreas, and later becomes more restricted to the hepatopancreatic ducts and pancreatic islets, including the insulin producing β-cells. Although Anxa4 is a known target of several monogenic diabetes genes and its elevated expression is associated with chemoresistance in malignancy, its in vivo role is largely unexplored. Knockdown of Anxa4 in zebrafish leads to elevated expression of caspase 8 and Δ113p53, and liver bud specific activation of Caspase 3 and apoptosis. Mosaic knockdown reveal that Anxa4 is required cell-autonomously in the liver bud for cell survival. This finding is further corroborated with mosaic anxa4 knockout studies using the CRISPR/Cas9 system. Collectively, we identify Anxa4 as a new, evolutionarily conserved hepatopancreatic factor that is required in zebrafish for liver progenitor viability, through inhibition of the extrinsic apoptotic pathway. A role for Anxa4 in cell survival may have implications for the mechanism of diabetic β-cell apoptosis and cancer cell chemoresistance. PMID:25176043

  7. IL-36-Induced Toxicity in Neonatal Mice Involves TNF-α Production by Liver Myeloid Cells.

    PubMed

    Palomo, Jennifer; Mastelic-Gavillet, Beatris; Woldt, Estelle; Troccaz, Sabina; Rodriguez, Emiliana; Palmer, Gaby; Siegrist, Claire-Anne; Gabay, Cem

    2016-09-15

    Human and mouse neonates exhibit limited vaccine responses characterized by predominant Th2 and limited Th1 responses. Because IL-36 exerts a synergic adjuvant effect with IL-12, enhancing Th1 polarization in adult (AD) mice, we administered IL-36β to neonatal (1-wk old) and AD control mice at the time of immunization with tetanus toxoid adsorbed to aluminum hydroxide (TT/Alum). Unexpectedly, the combination of IL-36β with TT/Alum, which was well tolerated in AD mice, proved toxic and even lethal in neonates. This neonatal toxicity was associated with high Il36r mRNA expression in neonatal liver, resulting in increased cytokine production. Liver Il36r mRNA expression decreased with the termination of fetal liver hematopoiesis, and this decrease correlated with a complete protection from TT/Alum/IL-36β-induced mortality. The combination of IL-36β and TT/Alum induced the rapid production of TNF-α and IFN-γ by liver myeloid and lymphoid cells, respectively. These responses were less marked when IL-36β was used alone, with no adverse effect. The toxicity of IL-36β + TT/Alum was abrogated by the administration of a neutralizing anti-TNF-α Ab, confirming causality. In conclusion, liver myeloid cells in neonatal mice are an important source of proinflammatory cytokines that may lead to TNF-α-mediated toxicity and even lethality. PMID:27527592

  8. Fluoride-induced oxidative stress is involved in the morphological damage and dysfunction of liver in female mice.

    PubMed

    Zhou, Bian-hua; Zhao, Jing; Liu, Jeffrey; Zhang, Ji-liang; Li, Jian; Wang, Hong-wei

    2015-11-01

    Fluoride (F), one of the most toxic environmental and industrial pollutants, is known to exert hepatotoxicity. The contribution of oxidative stress to the F tolerance of liver remains largely unknown. In this study, the morphological and ultrastructural characteristics of liver were observed using hematoxylin and eosin staining and transmission electron microscopy (TEM), respectively. Oxidative-stress participations was analysed and the mRNA expression levels of catalase (Cat), glutathione peroxidase 1 (GSH-Px1), nitric oxide synthase 2 (NOS2), and superoxide dismutase 1 (SOD1) were investigated by real-time PCR. Changes in liver-function parameters were also detected. Results showed that the reactive content of reactive oxygen species increased significantly, whereas SOD and GSH-Px activities, as well as total anti-oxidising capability (T-AOC), decreased significantly, with increased nitric oxide (NO) and malondialdehyde (MDA) contents in liver and serum after 70days of F treatment. The mRNA expression levels of Cat, GSH-Px1, and SOD were significantly downregulated, whereas NOS2 mRNA expression level was up upregulated, after F treatment for 70days. Light microscopy also revealed that hepatocytes were fused into pieces; cell boundaries were unclear, and nuclei were lightly stained. TEM further showed that hepatocytes were characterised by vague nuclear and mitochondrial membranes, dilated endoplasmic reticulum, and aggravated vacuolar degeneration. Activities of alanine transaminase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase, as well as the level of total bilirubin in serum increased. Overall, these results indicated that F interfered with the balance of antioxidase activity and morphological changes in liver, which were involved in mouse liver dysfunction. PMID:26295688

  9. Comparison of total lipids and fatty acids from liver, heart and abdominal muscle of scalloped (Sphyrna lewini) and smooth (Sphyrna zygaena) hammerhead sharks.

    PubMed

    Davidson, Bruce Clement; Nel, Wynand; Rais, Afsha; Namdarizandi, Vahid; Vizarra, Scott; Cliff, Geremy

    2014-01-01

    Liver, heart and abdominal muscle samples from scalloped (Sphyrna lewini) and smooth (Sphyrna zygaena) hammerhead sharks were analysed to characterise their lipid and fatty acid profiles. Samples were compared both between and within species, but there were no significant differences in total lipids for either comparison, although much greater total amounts were found in the liver samples. Within the individual fatty acids, the only significant differences were greater amounts of 22:6n-3, total n-3 polyunsaturates and total polyunsaturates in smooth, when compared to scalloped, hammerhead liver. This may reflect the more wide spread distribution of this species into cooler waters. Within both species the liver levels of the same fatty acid fractions decreased from spring to summer, which may correlate with changes in fatty acid profile to adapt to any differences in amount or species of prey consumed, or other considerations, eg. buoyancy, however there was no data to clarify this. PMID:25279312

  10. Acute Exercise Improves Insulin Clearance and Increases the Expression of Insulin-Degrading Enzyme in the Liver and Skeletal Muscle of Swiss Mice.

    PubMed

    Kurauti, Mirian A; Freitas-Dias, Ricardo; Ferreira, Sandra M; Vettorazzi, Jean F; Nardelli, Tarlliza R; Araujo, Hygor N; Santos, Gustavo J; Carneiro, Everardo M; Boschero, Antonio C; Rezende, Luiz F; Costa-Júnior, José M

    2016-01-01

    The effects of exercise on insulin clearance and IDE expression are not yet fully elucidated. Here, we have explored the effect of acute exercise on insulin clearance and IDE expression in lean mice. Male Swiss mice were subjected to a single bout of exercise on a speed/angle controlled treadmill for 3-h at approximately 60-70% of maximum oxygen consumption. As expected, acute exercise reduced glycemia and insulinemia, and increased insulin tolerance. The activity of AMPK-ACC, but not of IR-Akt, pathway was increased in the liver and skeletal muscle of trained mice. In an apparent contrast to the reduced insulinemia, glucose-stimulated insulin secretion was increased in isolated islets of these mice. However, insulin clearance was increased after acute exercise and was accompanied by increased expression of the insulin-degrading enzyme (IDE), in the liver and skeletal muscle. Finally, C2C12, but not HEPG2 cells, incubated at different concentrations of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) for 3-h, showed increased expression of IDE. In conclusion, acute exercise increases insulin clearance, probably due to an augmentation of IDE expression in the liver and skeletal muscle. The elevated IDE expression, in the skeletal muscle, seems to be mediated by activation of AMPK-ACC pathway, in response to exercise. We believe that the increase in the IDE expression, comprise a safety measure to maintain glycemia at or close to physiological levels, turning physical exercise more effective and safe. PMID:27467214

  11. Acute Exercise Improves Insulin Clearance and Increases the Expression of Insulin-Degrading Enzyme in the Liver and Skeletal Muscle of Swiss Mice

    PubMed Central

    Ferreira, Sandra M.; Vettorazzi, Jean F.; Nardelli, Tarlliza R.; Araujo, Hygor N.; Santos, Gustavo J.; Carneiro, Everardo M.; Boschero, Antonio C.; Rezende, Luiz F.; Costa-Júnior, José M.

    2016-01-01

    The effects of exercise on insulin clearance and IDE expression are not yet fully elucidated. Here, we have explored the effect of acute exercise on insulin clearance and IDE expression in lean mice. Male Swiss mice were subjected to a single bout of exercise on a speed/angle controlled treadmill for 3-h at approximately 60–70% of maximum oxygen consumption. As expected, acute exercise reduced glycemia and insulinemia, and increased insulin tolerance. The activity of AMPK-ACC, but not of IR-Akt, pathway was increased in the liver and skeletal muscle of trained mice. In an apparent contrast to the reduced insulinemia, glucose-stimulated insulin secretion was increased in isolated islets of these mice. However, insulin clearance was increased after acute exercise and was accompanied by increased expression of the insulin-degrading enzyme (IDE), in the liver and skeletal muscle. Finally, C2C12, but not HEPG2 cells, incubated at different concentrations of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) for 3-h, showed increased expression of IDE. In conclusion, acute exercise increases insulin clearance, probably due to an augmentation of IDE expression in the liver and skeletal muscle. The elevated IDE expression, in the skeletal muscle, seems to be mediated by activation of AMPK-ACC pathway, in response to exercise. We believe that the increase in the IDE expression, comprise a safety measure to maintain glycemia at or close to physiological levels, turning physical exercise more effective and safe. PMID:27467214

  12. Enzyme activities support the use of liver lipid-derived ketone bodies as aerobic fuels in muscle tissues of active sharks.

    PubMed

    Watson, R R; Dickson, K A

    2001-01-01

    Few data exist to test the hypothesis that elasmobranchs utilize ketone bodies rather than fatty acids for aerobic metabolism in muscle, especially in continuously swimming, pelagic sharks, which are expected to be more reliant on lipid fuel stores during periods between feeding bouts and due to their high aerobic metabolic rates. Therefore, to provide support for this hypothesis, biochemical indices of lipid metabolism were measured in the slow-twitch, oxidative (red) myotomal muscle, heart, and liver of several active shark species, including the endothermic shortfin mako, Isurus oxyrinchus. Tissues were assayed spectrophotometrically for indicator enzymes of fatty acid oxidation (3-hydroxy-o-acyl-CoA dehydrogenase), ketone-body catabolism (3-oxoacid-CoA transferase), and ketogenesis (hydroxy-methylglutaryl-CoA synthase). Red muscle and heart had high capacities for ketone utilization, low capacities for fatty acid oxidation, and undetectable levels of ketogenic enzymes. Liver demonstrated undetectable activities of ketone catabolic enzymes but high capacities for fatty acid oxidation and ketogenesis. Serum concentrations of the ketone beta-hydroxybutyrate varied interspecifically (means of 0.128-0.978 micromol mL(-1)) but were higher than levels previously reported for teleosts. These results are consistent with the hypothesis that aerobic metabolism in muscle tissue of active sharks utilizes ketone bodies, and not fatty acids, derived from liver lipid stores. PMID:11247746

  13. Exercise-Induced Changes in Caveolin-1, Depletion of Mitochondrial Cholesterol, and the Inhibition of Mitochondrial Swelling in Rat Skeletal Muscle but Not in the Liver.

    PubMed

    Flis, Damian Jozef; Olek, Robert Antoni; Kaczor, Jan Jacek; Rodziewicz, Ewa; Halon, Malgorzata; Antosiewicz, Jedrzej; Wozniak, Michal; Gabbianelli, Rosita; Ziolkowski, Wieslaw

    2016-01-01

    The reduction in cholesterol in mitochondria, observed after exercise, is related to the inhibition of mitochondrial swelling. Caveolin-1 (Cav-1) plays an essential role in the regulation of cellular cholesterol metabolism and is required by various signalling pathways. Therefore, the aim of this study was to investigate the effect of prolonged swimming on the mitochondrial Cav-1 concentration; additionally, we identified the results of these changes as they relate to the induction of changes in the mitochondrial swelling and cholesterol in rat skeletal muscle and liver. Male Wistar rats were divided into a sedentary control group and an exercise group. The exercised rats swam for 3 hours and were burdened with an additional 3% of their body weight. After the cessation of exercise, their quadriceps femoris muscles and livers were immediately removed for experimentation. The exercise protocol caused an increase in the Cav-1 concentration in crude muscle mitochondria; this was related to a reduction in the cholesterol level and an inhibition of mitochondrial swelling. There were no changes in rat livers, with the exception of increased markers of oxidative stress in mitochondria. These data indicate the possible role of Cav-1 in the adaptive change in the rat muscle mitochondria following exercise. PMID:26839631

  14. Whole-Body Muscle MRI in Patients with Hyperkalemic Periodic Paralysis Carrying the SCN4A Mutation T704M: Evidence for Chronic Progressive Myopathy with Selective Muscle Involvement

    PubMed Central

    Lee, Young Han; Lee, Hyung-Soo; Lee, Hyo Eun; Hahn, Seok; Nam, Tai-Seung; Choi, Young-Chul; Kim, Seung Min

    2015-01-01

    Background and Purpose Hyperkalemic periodic paralysis (hyperKPP) is a muscle sodium-ion channelopathy characterized by recurrent paralytic attacks. A proportion of affected individuals develop fixed or chronic progressive weakness that results in significant disability. However, little is known about the pathology of hyperKPP-induced fixed weakness, including the pattern of muscle involvement. The aim of this study was to characterize the patterns of muscle involvement in hyperKPP by whole-body magnetic resonance imaging (MRI). Methods We performed whole-body muscle MRI in seven hyperKPP patients carrying the T704M mutation in the SCN4A skeletal sodium-channel gene. Muscle fat infiltration, suggestive of chronic progressive myopathy, was analyzed qualitatively using a grading system and was quantified by the two-point Dixon technique. Results Whole-body muscle MRI analysis revealed muscle atrophy and fatty infiltration in hyperKPP patients, especially in older individuals. Muscle involvement followed a selective pattern, primarily affecting the posterior compartment of the lower leg and anterior thigh muscles. The muscle fat fraction increased with patient age in the anterior thigh (r=0.669, p=0.009), in the deep posterior compartment of the lower leg (r=0.617, p=0.019), and in the superficial posterior compartment of the lower leg (r=0.777, p=0.001). Conclusions Our whole-body muscle MRI findings provide evidence for chronic progressive myopathy in hyperKPP patients. The reported data suggest that a selective pattern of muscle involvement-affecting the posterior compartment of the lower leg and the anterior thigh-is characteristic of chronic progressive myopathy in hyperKPP. PMID:26256659

  15. The involvement of ankle muscles in maintaining balance in the upright posture is higher in elderly fallers.

    PubMed

    Cattagni, T; Scaglioni, G; Laroche, D; Gremeaux, V; Martin, A

    2016-05-01

    The purpose of this study was to determine whether the mechanical contribution of ankle muscles in the upright stance differed among young adults (YA) (n=10, age: ~24.3), elderly non-fallers (ENF) (n=12, age: ~77.3) and elderly fallers (EF) (n=20, age: ~80.7). Torque and electromyographic (EMG) activity were recorded on the triceps surae and tibialis anterior during maximum and submaximum contractions in the seated position. EMG activity was also recorded in subjects standing still. Plantar flexor (PF) and dorsal flexor (DF) torques generated in the upright posture were estimated from the torque-EMG relationship obtained during submaximum contractions in the seated position. Center of pressure (CoP) displacement was measured to quantify postural stability. Results showed that, in upright standing, EF generated greater ankle muscle relative torque (i.e. PF+DF torque in the upright stance/PF+DF during maximum isometric torque) than non-fallers (i.e. ENF, YA). The greater involvement of ankle muscles in EF was associated with higher CoP displacement. PF+DF torque in the upright stance was no different among the groups, but PF+DF torque during maximum effort was impaired in older groups compared with YA and was lower in EF than ENF. These results suggest that the postural stability impairment observed with aging is highly related to ankle muscle weakness. PMID:26899564

  16. TNF-α is involved in activating DNA fragmentation in skeletal muscle

    PubMed Central

    Carbó, N; Busquets, S; van Royen, M; Alvarez, B; López-Soriano, F J; Argilés, J M

    2002-01-01

    Intraperitoneal administration of 100 μg kg−1 (body weight) of tumour necrosis factor-α to rats for 8 consecutive days resulted in a significant decrease in protein content, which was concomitant with a reduction in DNA content. Interestingly, the protein/DNA ratio was unchanged in the skeletal muscle of the tumour necrosis factor-α-treated animals as compared with the non-treated controls. Analysis of muscle DNA fragmentation clearly showed enhanced laddering in the skeletal muscle of tumour necrosis factor-α-treated animals, suggesting an apoptotic phenomenon. In a different set of experiments, mice bearing a cachexia-inducing tumour (the Lewis lung carcinoma) showed an increase in muscle DNA fragmentation (9.8-fold) as compared with their non-tumour-bearing control counterparts as previously described. When gene-deficient mice for tumour necrosis factor-α receptor protein I were inoculated with Lewis lung carcinoma, they were also affected by DNA fragmentation; however the increase was only 2.1-fold. These results suggest that tumour necrosis factor-α partly mediates DNA fragmentation during experimental cancer-associated cachexia. British Journal of Cancer (2002) 86, 1012–1016. DOI: 10.1038/sj/bjc/6600167 www.bjcancer.com © 2002 Cancer Research UK PMID:11953838

  17. Orbital Volumetry in Graves' Orbitopathy: Muscle and Fat Involvement in relation to Dysthyroid Optic Neuropathy.

    PubMed

    Al-Bakri, Moug; Rasmussen, Ase Krogh; Thomsen, Carsten; Toft, Peter Bjerre

    2014-01-01

    Purpose. We wanted to investigate the relative significance of fat and muscle enlargement in the development of dysthyroid optic neuropathy (DON) in Graves' orbitopathy (GO). Methods. Preoperative coronal CT scans of 13 patients with and without DON who subsequently underwent orbital decompression were retrospectively analyzed. Thirteen patients imaged for unilateral orbital fractures served as controls. Results. The retrobulbar muscle volume was 2.1 ± 0.5 cm(3) (mean ± SD) in controls, 4.3 ± 1.5 cm(3) in GO without DON, and 4.7 ± 1.7 cm(3) in GO with DON. The retrobulbar fat volume was 5.4 ± 1.6 cm(3) in controls, 8.7 ± 8.0 cm(3) in GO without DON, and 9.4 ± 3.1 cm(3) in GO with DON. The muscle and fat volumes were higher in patients with GO than in controls (P < 0.001), but the volumes in orbits with and without DON were not significantly different. The volume of the optic nerve were similar in the 3 groups. The number of apical, coronal 2 mm thick slices with no fat was 2.9 ± 0.9 in normal orbits, it was 4.1 ± 1.0 in GO orbits without DON and 5.3 ± 0.8 in GO orbits with DON (P = 0.007). Conclusion. Apical muscle enlargement may be more important than orbital fat enlargement in the development of DON. However, the fact that apical crowding and muscle enlargement also occur in orbits without DON suggests that other factors also play a role in the development of DON. PMID:25101183

  18. Tc-99m colloid lung uptake in a rare case of toxoplasmosis with liver involvement

    SciTech Connect

    Garty, I.; Tal, I.; Kaynan, A.

    1984-06-01

    Intensive lung accumulation of colloid (Tc-99m phytate) was demonstrated in a child suffering from acquired toxoplasmosis with a rare manifestation of severe liver damage. The possible mechanism and clinical importance of colloid lung concentration in this case is briefly discussed, including a review of the literature on this subject.

  19. Effect of Intermittent Hypoxia and Rimonabant on Glucose Metabolism in Rats: Involvement of Expression of GLUT4 in Skeletal Muscle

    PubMed Central

    Wang, Xiaoya; Yu, Qin; Yue, Hongmei; Zeng, Shuang; Cui, Fenfen

    2015-01-01

    Background Obstructive sleep apnea (OSA) and its main feature, chronic intermittent hypoxia (IH) during sleep, is closely associated with insulin resistance (IR) and diabetes. Rimonabant can regulate glucose metabolism and improve IR. The present study aimed to assess the effect of IH and rimonabant on glucose metabolism and insulin sensitivity, and to explore the possible mechanisms. Material/Methods Thirty-two rats were randomly assigned into 4 groups: Control group, subjected to intermittent air only; IH group, subjected to IH only; IH+NS group, subjected to IH and treated with normal saline; and IH+Rim group, subjected to IH and treated with 10 mg/kg/day of rimonabant. All rats were killed after 28 days of exposure. Then, the blood and skeletal muscle were collected. We measured fasting blood glucose levels, fasting blood insulin levels, and the expression of glucose transporter 4 (GLUT4) in both mRNA and protein levels in skeletal muscle. Results IH can slow weight gain, increase serum insulin level, and reduce insulin sensitivity in rats. The expressions of GLUT4 mRNA, total GLUT4, and plasma membrane protein of GLUT4 (PM GLUT4) in skeletal muscle were decreased. Rimonabant treatment was demonstrated to improve weight gain and insulin sensitivity of the rats induced by IH. Rimonabant significantly upregulated the expression of GLUT4 mRNA, PM GLUT4, and total GLUT4 in skeletal muscle. Conclusions The present study demonstrates that IH can cause IR and reduced expression of GLUT4 in both mRNA and protein levels in skeletal muscle of rats. Rimonabant treatment can improve IH – induced IR, and the upregulation of GLUT4 expression may be involved in this process. PMID:26503060

  20. Striated muscle involvement in experimental oral infection by herpes simplex virus type 1.

    PubMed

    Gonzalez, María Inés; Sanjuan, Norberto A

    2013-07-01

    Herpes simplex virus type 1 is one of the most frequent causes of oral infection in humans, especially during early childhood. Several experimental models have been developed to study the pathogenesis of this virus but all of them employed adult animals. In this work, we developed an experimental model that uses mice younger than 4 days old, to more closely resemble human infection. Mice were infected subcutaneously with the prototype strain McIntyre of Herpes simplex-1, and the progression of infection was studied by immunoperoxidase. All animals died within 24-72 h post-infection, while viral antigens were found in the oral epithelium, nerves and brain. The most striking result was the finding of viral antigens in the nucleus and cytoplasm of cells belonging to striated muscles. Organotypic cultures of striated muscles were performed, and viral replication was observed in them by immunocytochemistry, electron microscopy and viral isolation. We conclude that the infection of striated muscles is present from the onset of oral infection and, eventually, could explain some clinical observations in humans. PMID:23445118

  1. The effect of production system and age on levels of iron, taurine, carnosine, coenzyme Q(10), and creatine in beef muscles and liver.

    PubMed

    Purchas, R W; Busboom, J R

    2005-08-01

    Samples of longissimus (LL) and triceps brachii (TB) muscles from Angus-cross heifers finished either on a high-concentrate ration in Washington, USA, (US cattle, n=15) or on pasture in New Zealand (NZ cattle, n=16) were assessed for composition characteristics. Half of the NZ cattle were of a similar age to the US cattle (NZAge) and half were of a similar weight (NZWt). Iron concentration was higher in TB (20.9 vs. 17.5μgg(-1); P<0.001) and was higher for the NZWt group than the NZAge group or the US cattle. The proportion of iron as haem iron was highest for the NZWt group (87.3%; P<0.01), but the proportion as soluble haem iron was highest for the US cattle. For a sub-group of 10 pasture-finished cattle, iron levels in cheek muscle were higher than for LL or TB, and liver levels were 66% higher than cheek muscle. The proportion of haem iron, however, was lowest in liver (55.3%) and was lower in cheek muscle (78.4%) than LL or TB. Relative to LL, TB had higher levels of taurine and coenzyme Q(10), but lower levels of carnosine, creatine and creatinine, as expected for a muscle with a more aerobic metabolism. These differences were magnified for the even more aerobic cheek muscle. Differences between the two NZ groups were small, but muscles from the US cattle contained less taurine, carnosine, coenzyme Q(10), and creatinine. Reasons for these differences in various meat components for similar cattle from different production systems are not clear. PMID:22063884

  2. Molecular characterization of betaine-homocysteine methyltransferase 1 from the liver, and effects of aestivation on its expressions and homocysteine concentrations in the liver, kidney and muscle, of the African lungfish, Protopterus annectens.

    PubMed

    Ong, Jasmine L Y; Woo, Jia M; Hiong, Kum C; Ching, Biyun; Wong, Wai P; Chew, Shit F; Ip, Yuen K

    2015-05-01

    Homocysteine accumulation has numerous deleterious effects, and betaine-homocysteine S-methyltransferase (BHMT) catalyses the synthesis of methionine from homocysteine and betaine. This study aimed to determine homocysteine concentrations, and mRNA expression levels and protein abundances of bhmt1/Bhmt1 in the liver, kidney and muscle of the African lungfish, Protopterus annectens, during the induction (6 days), maintenance (6 months) or arousal (3 days after arousal) phase of aestivation. The homocysteine concentration decreased significantly in the liver of P. annectens after 6 days or 6 months of aestivation, but it returned to the control level upon arousal. By contrast, homocysteine concentrations in the kidney and muscle remained unchanged during the three phases of aestivation. The complete coding cDNA sequence of bhmt1 from P. annectens consisted of 1236 bp, coding for 412 amino acids. The Bhmt1 from P. annectens had a close phylogenetic relationship with those from tetrapods and Callorhinchus milii. The expression of bhmt1 was detected in multiple organs/tissues of P. annectens, and this is the first report on the expression of bhmt1/Bhmt1 in animal skeletal muscle. The mRNA and protein expression levels of bhmt1/Bhmt1 were up-regulated in the liver of P. annectens during the induction and maintenance phases of aestivation, possibly to regulate the hepatic homocysteine concentration. The significant increase in hepatic Bhmt1 protein abundance during the arousal phase could be a response to increased cellular methylation for the purpose of tissue reconstruction. Unlike the liver, Bhmt1 expression in the kidney and muscle of P. annectens was regulated translationally, and its up-regulation could be crucial to prevent homocysteine accumulation. PMID:25575738

  3. Induction of liver alpha-1 acid glycoprotein gene expression involves both positive and negative transcription factors.

    PubMed Central

    Lee, Y M; Tsai, W H; Lai, M Y; Chen, D S; Lee, S C

    1993-01-01

    Expression of the alpha-1 acid glycoprotein (AGP) gene is liver specific and acute phase responsive. Within the 180-bp region of the AGP promoter, at least five cis elements have been found to interact with trans-acting factors. Four of these elements (A, C, D, and E) interacted with AGP/EBP, a liver-enriched transcription factor, as shown by footprinting analysis and by an anti-AGP/EBP antibody-induced supershift in a gel retardation assay. Modification of these sites by site-directed mutagenesis coupled with transfection analysis indicated that AGP/EBP binding to all of these sites resulted in positive regulation of the promoter. Dose-response data suggest that AGP/EBP binding to these sites results in the cooperative activation of the promoter. In contrast, functional assays showed that element B is a negative regulatory element; this element is recognized by heat-stable DNA-binding factors which are found in many cells and tissues. The regulation of these binding proteins was studied in rat liver treated with lipopolysaccharide (LPS), which induced an acute-phase reaction. We found that LPS treatment resulted in a two- to threefold increase in AGP/EBP activity and a severalfold decrease in the activity of factors that bind to element B in the liver. These results indicate that expression of the AGP gene can be regulated by both positive and negative factors and that the modulation of these factors can account for the LPS induction of the AGP gene. Images PMID:8417341

  4. Hepatoprotective effects of lycopene on liver enzymes involved in methionine and xenobiotic metabolism in hyperhomocysteinemic rats.

    PubMed

    Yefsah-Idres, Aicha; Benazzoug, Yasmina; Otman, Amel; Latour, Alizée; Middendorp, Sandrine; Janel, Nathalie

    2016-06-15

    Hyperhomocysteinemia, defined by an increased plasma homocysteine level, is commonly associated with chronic liver diseases. A link between the elevated homocysteine level and oxidative stress has been demonstrated. Indeed the pathogenesis of liver diseases in the case of hyperhomocysteinemia could be due to this production of oxidative stress. Many studies have demonstrated the antioxidative properties of lycopene, a carotenoid. Therefore, the present study was designed to induce hyperhomocysteinemia in male Wistar rats in order to analyze the effect of lycopene supplementation on homocysteine metabolism, on phase I and phase II xenobiotic-metabolizing enzyme activities, and on liver injury by histological examination and analysis of biochemical markers. We found that rats with a high methionine diet showed abnormal histological features, with an increase of serum homocysteine, alanine aminotransferase and aspartate aminotransferase levels, decreased hepatic cystathionine beta synthase and S-adenosyl-homocysteine hydrolase activities and an increased hepatic malondialdehyde level. We demonstrated the reversal effect of lycopene supplementation on hyperhomocysteinemia. Taken together, these findings provide additional clues on the hepatoprotective effects of lycopene. PMID:27232443

  5. Exogenous hepatitis B virus envelope proteins induce endoplasmic reticulum stress: involvement of cannabinoid axis in liver cancer cells

    PubMed Central

    Montalbano, Roberta; Honrath, Birgit; Wissniowski, Thaddeus Till; Elxnat, Moritz; Roth, Silvia; Ocker, Matthias; Quint, Karl; Churin, Yuri; Roederfeld, Martin; Schroeder, Dirk; Glebe, Dieter; Roeb, Elke; Fazio, Pietro Di

    2016-01-01

    HBV represents the most common chronic viral infection and major cause of hepatocellular carcinoma (HCC), although its exact role in liver tumorigenesis is unclear. Massive storage of the small (SHBs), middle (MHBs) and large surface (LHBs) HBV envelope proteins leads to cell stress and sustained inflammatory responses. Cannabinoid (CB) system is involved in the pathogenesis of liver diseases, stimulating acute and chronic inflammation, liver damage and fibrogenesis; it triggers endoplasmic reticulum (ER) stress response. The aim of our work was to investigate the activation of ER stress pathway after ectopic HBV envelope proteins expression, in liver cancer cells, and the role exerted by CB receptors. PCR, immunofluorescence and western blotting showed that exogenous LHBs and MHBs induce a clear ER stress response in Huh-7 cells expressing CB1 receptor. Up-regulation of the chaperone BiP/GRP78 (Binding Immunoglobulin Protein/Glucose-Regulated Protein 78) and of the transcription factor CHOP/GADD153 (C/EBP Homologous Protein/Growth Arrest and DNA Damage inducible gene 153), phosphorylation of PERK (PKR-like ER Kinase) and eIF2α (Eukaryotic Initiation Factor 2α) and splicing of XBP1 (X-box binding protein 1) was observed. CB1−/− HepG2 cells did not show any ER stress activation. Inhibition of CB1 receptor counteracted BiP expression in transfected Huh-7 and in HBV+ PLC/PRF/5 cells; whereas no effect was observed in HBV− HLF cells. These results suggest that HBV envelope proteins are able to induce the ER stress pathway. CB1 expression is directly correlated with ER stress function. Further investigations are needed to clarify the involvement of cannabinoid in HCC progression after HBV infection. PMID:26967385

  6. Genetic variability of transcript abundance in pig peri-mortem skeletal muscle: eQTL localized genes involved in stress response, cell death, muscle disorders and metabolism

    PubMed Central

    2011-01-01

    Background The genetics of transcript-level variation is an exciting field that has recently given rise to many studies. Genetical genomics studies have mainly focused on cell lines, blood cells or adipose tissues, from human clinical samples or mice inbred lines. Few eQTL studies have focused on animal tissues sampled from outbred populations to reflect natural genetic variation of gene expression levels in animals. In this work, we analyzed gene expression in a whole tissue, pig skeletal muscle sampled from individuals from a half sib F2 family shortly after slaughtering. Results QTL detection on transcriptome measurements was performed on a family structured population. The analysis identified 335 eQTLs affecting the expression of 272 transcripts. The ontologic annotation of these eQTLs revealed an over-representation of genes encoding proteins involved in processes that are expected to be induced during muscle development and metabolism, cell morphology, assembly and organization and also in stress response and apoptosis. A gene functional network approach was used to evidence existing biological relationships between all the genes whose expression levels are influenced by eQTLs. eQTLs localization revealed a significant clustered organization of about half the genes located on segments of chromosome 1, 2, 10, 13, 16, and 18. Finally, the combined expression and genetic approaches pointed to putative cis-drivers of gene expression programs in skeletal muscle as COQ4 (SSC1), LOC100513192 (SSC18) where both the gene transcription unit and the eQTL affecting its expression level were shown to be localized in the same genomic region. This suggests cis-causing genetic polymorphims affecting gene expression levels, with (e.g. COQ4) or without (e.g. LOC100513192) potential pleiotropic effects that affect the expression of other genes (cluster of trans-eQTLs). Conclusion Genetic analysis of transcription levels revealed dependence among molecular phenotypes as being

  7. Effects of acute exercise on lipid content and dietary lipid uptake in liver and skeletal muscle of lean and diabetic rats.

    PubMed

    Janssens, Sharon; Jonkers, Richard A M; Groen, Albert K; Nicolay, Klaas; van Loon, Luc J C; Prompers, Jeanine J

    2015-11-15

    Insulin resistance is associated with ectopic lipid accumulation. Physical activity improves insulin sensitivity, but the impact of exercise on lipid handling in insulin-resistant tissues remains to be elucidated. The present study characterizes the effects of acute exercise on lipid content and dietary lipid partitioning in liver and skeletal muscle of lean and diabetic rats by use of magnetic resonance spectroscopy (MRS). After baseline measurements, rats were randomized to exercise or no-exercise groups. A subset of animals was subjected to MRS directly after 1 h of treadmill running for measurement of total intrahepatocellular lipid (IHCL) and intramyocellular lipid (IMCL) content (n=7 lean and diabetic rats). The other animals were administered 13C-labeled lipids orally after treadmill visit (with or without exercise) followed by MRS measurements after 4 and 24 h to determine the 13C enrichment of IHCL and IMCL (n=8 per group). Total IHCL and IMCL content were fivefold higher in diabetic vs. lean rats (P<0.001). Exercise did not significantly affect IHCL content but reduced IMCL by 25±7 and 33±4% in lean and diabetic rats (P<0.05), respectively. Uptake of dietary lipids in liver and muscle was 2.3-fold greater in diabetic vs. lean rats (P<0.05). Prior exercise did not significantly modulate dietary lipid uptake into muscle, but in liver of both lean and diabetic rats, lipid uptake was 44% reduced after acute exercise (P<0.05). In conclusion, IMCL but not IHCL represents a viable substrate source during exercise in both lean and diabetic rats, and exercise differentially affects dietary lipid uptake in muscle and liver. PMID:26419590

  8. Spectrofluorimetric analysis of ethopabate in veterinary formulations with application to residue determination in chicken muscles and liver.

    PubMed

    Nasr, Jenny Jeehan; Shalan, Shereen

    2014-12-01

    Ethopabate is a veterinary drug used in the prophylaxis and treatment of coccidiosis in chickens. The presence of drug residues in edible tissues can be dangerous to human consumers. It may cause direct toxic effects, allergic reactions and increased bacterial resistance. A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of ethopabate in its veterinary formulations. The proposed method is based on measuring the native fluorescence of ethopabate in water at 364 nm after excitation at 270 nm. The fluorescence-concentration plot was rectilinear over the range of 2-100 ng/mL, with a limit of detection of 2.9 ng/g and a limit of quantification of 9.8 ng/g for ethopabate. The method was successfully applied to the analysis of ethopabate in its commercial veterinary formulations and the results were in good agreement with those obtained with the reference method. The method was extended to the determination of ethopabate residues in chicken muscles and liver, and the results were satisfactory. The recoveries obtained were in the 108.36-113.42% range. No organic solvents are used in the procedure, so it can be considered a type of 'green' chemistry. PMID:24817251

  9. Duration of transport and holding in lairage at constant postprandial delay to slaughter--effects on fatty liver and breast muscle quality in mule ducks.

    PubMed

    Fernandez, X; Bouillier-Oudot, M; Molette, C; Bernadet, M D; Manse, H

    2011-10-01

    The present study was designed to evaluate the effect of preslaughter transport (30 vs. 150 min) and holding of mule ducks in lairage in their transport crates (15 vs. 120 min) on the quality of the meat and fatty liver. A total of 120 birds were allocated in a 2 × 2 factorial design with a constant postprandial delay to slaughter (8 h), to avoid the confounding between the effects of the experimental treatments and those of fasting duration. Under such conditions, extending the transport or holding duration did not induce a loss in preslaughter live weight or liver weight. Similarly, breast muscle glycogen stores were not affected by the treatments, nor was the kinetics of postmortem pH decline affected. The mechanical resistance of raw meat obtained by the compression test significantly increased with holding duration. The gross chemical composition of the livers did not differ significantly among the preslaughter treatments. Residual blood in the liver, as indicated by heme pigment concentration, was enhanced with a longer transport, but this effect was more pronounced after the longest holding duration, as shown by a significant interaction. This, however, did not significantly affect the incidence of appearance defects or the commercial grading of the livers. The percentage of fat loss during the cooking of canned livers was significantly reduced when the transport duration was increased. This effect could not be explained on the basis of the current knowledge for determining the technological quality of fatty liver. The identification of biological markers of liver quality is currently underway in our laboratory. Further investigations studying the differential expression of these biological markers according to preslaughter conditions would provide a better understanding of the effect of transport duration on liver processing yield. PMID:21934021

  10. Placental restriction reduces insulin sensitivity and expression of insulin signaling and glucose transporter genes in skeletal muscle, but not liver, in young sheep.

    PubMed

    De Blasio, Miles J; Gatford, Kathryn L; Harland, M Lyn; Robinson, Jeffrey S; Owens, Julie A

    2012-05-01

    Poor growth before birth is associated with impaired insulin sensitivity later in life, increasing the risk of type 2 diabetes. The tissue sites at which insulin resistance first develops after intrauterine growth restriction (IUGR), and its molecular basis, are unclear. We have therefore characterized the effects of placental restriction (PR), a major cause of IUGR, on whole-body insulin sensitivity and expression of molecular determinants of insulin signaling and glucose uptake in skeletal muscle and liver of young lambs. Whole-body insulin sensitivity was measured at 30 d by hyperinsulinaemic euglycaemic clamp and expression of insulin signaling genes (receptors, pathways, and targets) at 43 d in muscle and liver of control (n = 15) and PR (n = 13) lambs. PR reduced size at birth and increased postnatal growth, fasting plasma glucose (+15%, P = 0.004), and insulin (+115%, P = 0.009). PR reduced whole-body insulin sensitivity (-43%, P < 0.001) and skeletal muscle expression of INSR (-36%), IRS1 (-28%), AKT2 (-44%), GLUT4 (-88%), GSK3α (-35%), and GYS1 (-31%) overall (each P < 0.05) and decreased AMPKγ3 expression in females (P = 0.030). PR did not alter hepatic expression of insulin signaling and related genes but increased GLUT2 expression (P = 0.047) in males. Whole-body insulin sensitivity correlated positively with skeletal muscle expression of IRS1, AKT2, HK, AMPKγ2, and AMPKγ3 in PR lambs only (each P < 0.05) but not with hepatic gene expression in control or PR lambs. Onset of insulin resistance after PR and IUGR is accompanied by, and can be accounted for by, reduced expression of insulin signaling and metabolic genes in skeletal muscle but not liver. PMID:22434080

  11. Perfluoroalkyl sulfonates and carboxylic acids in liver, muscle and adipose tissues of black-footed albatross (Phoebastria nigripes) from Midway Island, North Pacific Ocean.

    PubMed

    Chu, Shaogang; Wang, Jun; Leong, Gladys; Woodward, Lee Ann; Letcher, Robert J; Li, Qing X

    2015-11-01

    The Great Pacific Garbage Patch (GPGP) is a gyre of marine plastic debris in the North Pacific Ocean, and nearby is Midway Atoll which is a focal point for ecological damage. This study investigated 13 C4-C16 perfluorinated carboxylic acids (PFCAs), four (C4, C6, C8 and C10) perfluorinated sulfonates and perfluoro-4-ethylcyclohexane sulfonate [collectively perfluoroalkyl acids (PFAAs)] in black-footed albatross tissues (collected in 2011) from Midway Atoll. Of the 18 PFCAs and PFSAs monitored, most were detectable in the liver, muscle and adipose tissues. The concentrations of PFCAs and PFSAs were higher than those in most seabirds from the arctic environment, but lower than those in most of fish-eating water birds collected in the U.S. mainland. The concentrations of the PFAAs in the albatross livers were 7-fold higher than those in Laysan albatross liver samples from the same location reported in 1994. The concentration ranges of PFOS were 22.91-70.48, 3.01-6.59 and 0.53-8.35 ng g(-1) wet weight (ww), respectively, in the liver, muscle and adipose. In the liver samples PFOS was dominant, followed by longer chain PFUdA (8.04-18.70 ng g(-1) ww), PFTrDA, and then PFNA, PFDA and PFDoA. Short chain PFBA, PFPeA, PFBS and PFODA were below limit of quantification. C8-C13 PFCAs showed much higher composition compared to those found in other wildlife where PFOS typically predominated. The concentrations of PFUdA in all 8 individual albatross muscle samples were even higher than those of PFOS. This phenomenon may be attributable to GPGP as a pollution source as well as PFAA physicochemical properties. PMID:26037817

  12. Fatty-acid profiles of white muscle and liver in stream-maturing steelhead trout Oncorhynchus mykiss from early migration to kelt emigration.

    PubMed

    Penney, Z L; Moffitt, C M

    2015-01-01

    The profiles of specific fatty acids (FA) in white muscle and liver of fasting steelhead trout Oncorhynchus mykiss were evaluated at three periods during their prespawning migration and at kelt emigration in the Snake-Columbia River of Washington, Oregon and Idaho, to improve the understanding of energy change. Twenty-seven FAs were identified; depletion of 10 of these was positively correlated in liver and white muscle of prespawning O. mykiss. To observe relative changes in FA content more accurately over sampling intervals, the lipid fraction of tissues was used to normalize the quantity of individual FA to an equivalent tissue wet mass. Saturated and monounsaturated FAs were depleted between upstream migration in September and kelt emigration in June, whereas polyunsaturated FAs were more conserved. Liver was depleted of FAs more rapidly than muscle. Three FAs were detected across all sampling intervals: 16:0, 18:1 and 22:6n3, which are probably structurally important to membranes. When structurally important FAs of O. mykiss are depleted to provide energy, physiological performance and survival may be affected. PMID:25424636

  13. Fatty-acid profiles of white muscle and liver in stream-maturing steelhead trout Oncorhynchus mykiss from early migration to kelt emigration

    USGS Publications Warehouse

    Penney, Zachary L.; Moffitt, Christine M.

    2015-01-01

    The profiles of specific fatty acids (FA) in white muscle and liver of fasting steelhead troutOncorhynchus mykiss were evaluated at three periods during their prespawning migration and at kelt emigration in the Snake–Columbia River of Washington, Oregon and Idaho, to improve the understanding of energy change. Twenty-seven FAs were identified; depletion of 10 of these was positively correlated in liver and white muscle of prespawning O. mykiss. To observe relative changes in FA content more accurately over sampling intervals, the lipid fraction of tissues was used to normalize the quantity of individual FA to an equivalent tissue wet mass. Saturated and monounsaturated FAs were depleted between upstream migration in September and kelt emigration in June, whereas polyunsaturated FAs were more conserved. Liver was depleted of FAs more rapidly than muscle. Three FAs were detected across all sampling intervals: 16:0, 18:1 and 22:6n3, which are probably structurally important to membranes. When structurally important FAs of O. mykiss are depleted to provide energy, physiological performance and survival may be affected.

  14. Comparative transcriptomic analysis by RNA-seq to discern differential expression of genes in liver and muscle tissues of adult Berkshire and Jeju Native Pig.

    PubMed

    Sodhi, Simrinder Singh; Song, Ki-Duk; Ghosh, Mrinmoy; Sharma, Neelesh; Lee, Sung Jin; Kim, Jeong Hyun; Kim, Nameun; Mongre, Raj Kumar; Adhikari, Pradeep; Kim, Jin Young; Hong, Sang Pyo; Oh, Sung Jong; Jeong, Dong Kee

    2014-08-10

    RNA-seq is being rapidly adopted for the profiling of the transcriptomes in different areas of biology, especially in the studies related to gene regulation. The discovery of differentially expressed genes (DEGs) between adult animals of Jeju Native Pig (JNP) and Berkshire breeds of Sus scrofa, is of particular interest for the current study. For the better understanding of the gene expression profiles of the liver and longissimus dorsi muscle, DEGs were identified via RNA-seq. Sequence reads were obtained from Illumina HiSeq2000 and mapped to the pig reference genome (Sscrofa10.2) using Tophat2. We identified 169 and 39 DEGs in the liver and muscle of JNP respectively, by comparison with Berkshire breed. Out of all identified genes, 41 genes in the liver and 9 genes in the muscle have given significant expression. Gene ontology (GO) terms of developmental process and KEGG pathway analysis showed that metabolic, immune response and protein binding were commonly enriched pathways in the two tissues. Further the heat map analysis by ArrayStar has shown the different levels of expression in JNP with respect to the Berkshire breed. The validation through real time PCR and western blotting also confirmed the differential expression of genes in both breeds. Genes pertaining to metabolic process and inflammatory and immune system are more enriched in Berkshire breed. This comparative transcriptome analysis of two tissues suggests a subset of novel marker genes which expressed differently between the JNP and Berkshire. PMID:24910116

  15. The Transcriptional Effects of PCB118 and PCB153 on the Liver, Adipose Tissue, Muscle and Colon of Mice: Highlighting of Glut4 and Lipin1 as Main Target Genes for PCB Induced Metabolic Disorders

    PubMed Central

    Mesnier, Aurélia; Champion, Serge; Louis, Laurence; Sauzet, Christophe; May, Phealay; Portugal, Henri; Benbrahim, Karim; Abraldes, Joelle; Alessi, Marie-Christine; Amiot-Carlin, Marie-Josephe; Peiretti, Franck; Piccerelle, Philippe; Nalbone, Gilles; Villard, Pierre-Henri

    2015-01-01

    Epidemiological studies have associated environmental exposure to polychlorinated biphenyls (PCBs) with an increased risk of type 2 diabetes; however, little is known about the underlying mechanisms involved in the metabolic side-effects of PCB. Our study evaluated the transcriptional effects of a subchronic exposure (gavage at Day 0 and Day 15 with 10 or 100 μmol/Kg bw) to PCB118 (dioxin-like PCB), PCB153 (non-dioxin-like PCB), or an equimolar mixture of PCB118 and PCB153 on various tissues (liver, visceral adipose tissue, muscle, and colon) in mice. Our results showed that a short-term exposure to PCB118 and/or PCB153 enhanced circulating triglyceride levels but did not affect glycemia. Among the studied tissues, we did not observe any modification of the expression of inflammation-related genes, such as cytokines or chemokines. The main transcriptional effects were observed in visceral adipose and liver tissues. We found a downregulation of lipin1 and glut4 expression in these two target organs. In adipose tissue, we also showed a downregulation of Agpat2, Slc25a1, and Fasn. All of these genes are involved in lipid metabolism and insulin resistance. In muscles, we observed an induction of CnR1 and Foxo3 expression, which may be partly involved in PCB metabolic effects. In summary, our results suggest that lipin1 and glut4, notably in adipose tissue, are the main targeted genes in PCB-induced metabolic disorders, however, further studies are required to fully elucidate the mechanisms involved. PMID:26086818

  16. The Transcriptional Effects of PCB118 and PCB153 on the Liver, Adipose Tissue, Muscle and Colon of Mice: Highlighting of Glut4 and Lipin1 as Main Target Genes for PCB Induced Metabolic Disorders.

    PubMed

    Mesnier, Aurélia; Champion, Serge; Louis, Laurence; Sauzet, Christophe; May, Phealay; Portugal, Henri; Benbrahim, Karim; Abraldes, Joelle; Alessi, Marie-Christine; Amiot-Carlin, Marie-Josephe; Peiretti, Franck; Piccerelle, Philippe; Nalbone, Gilles; Villard, Pierre-Henri

    2015-01-01

    Epidemiological studies have associated environmental exposure to polychlorinated biphenyls (PCBs) with an increased risk of type 2 diabetes; however, little is known about the underlying mechanisms involved in the metabolic side-effects of PCB. Our study evaluated the transcriptional effects of a subchronic exposure (gavage at Day 0 and Day 15 with 10 or 100 μmol/Kg bw) to PCB118 (dioxin-like PCB), PCB153 (non-dioxin-like PCB), or an equimolar mixture of PCB118 and PCB153 on various tissues (liver, visceral adipose tissue, muscle, and colon) in mice. Our results showed that a short-term exposure to PCB118 and/or PCB153 enhanced circulating triglyceride levels but did not affect glycemia. Among the studied tissues, we did not observe any modification of the expression of inflammation-related genes, such as cytokines or chemokines. The main transcriptional effects were observed in visceral adipose and liver tissues. We found a downregulation of lipin1 and glut4 expression in these two target organs. In adipose tissue, we also showed a downregulation of Agpat2, Slc25a1, and Fasn. All of these genes are involved in lipid metabolism and insulin resistance. In muscles, we observed an induction of CnR1 and Foxo3 expression, which may be partly involved in PCB metabolic effects. In summary, our results suggest that lipin1 and glut4, notably in adipose tissue, are the main targeted genes in PCB-induced metabolic disorders, however, further studies are required to fully elucidate the mechanisms involved. PMID:26086818

  17. Exendin-4 agonist and exendin(9-39)amide antagonist of the GLP-1(7-36)amide effects in liver and muscle.

    PubMed

    Alcántara, A I; Morales, M; Delgado, E; López-Delgado, M I; Clemente, F; Luque, M A; Malaisse, W J; Valverde, I; Villanueva-Peñacarrillo, M L

    1997-05-01

    The GLP-1 structurally related peptides exendin-4 and exendin(9-39)amide were found to act, in rat liver and skeletal muscle, as agonist and antagonist, respectively, of the GLP-1(7-36)amide effects on glucose metabolism. Thus, like GLP-1(7-36)amide, exendin-4 increased glycogen synthase a activity and glucose incorporation into glycogen in both tissues and also stimulated exogenous D-glucose utilization and oxidation in muscle. These effects of GLP-1(7-36)amide and exendin-4 were inhibited by exendin(9-39)amide. Our findings provide further support to the proposed use of GLP-1, or exendin-4, as a tool in the treatment of diabetes mellitus. Thus, in addition to the well-known insulinotropic action of the peptides, they act both in liver and in muscle in a manner most suitable for restoration of glucose homeostasis, with emphasis on their positive effects upon glycogen synthesis in the two tissues and on the stimulation of exogenous glucose catabolism in muscle. PMID:9143346

  18. Effects of freshwater clam extract supplementation on time to exhaustion, muscle damage, pro/anti-inflammatory cytokines, and liver injury in rats after exhaustive exercise.

    PubMed

    Huang, Kuo-Chin; Wu, Wen-Tien; Yang, Fwu-Lin; Chiu, Yi-Han; Peng, Tai-Chu; Hsu, Bang-Gee; Liao, Kuang-Wen; Lee, Ru-Ping

    2013-01-01

    The potent anti-inflammatory activities and tissue-protective effects of freshwater clams (Corbicula fluminea) have been well reported. The aim of this study was to determine the effects of freshwater clam extract (FCE) supplementation on time to exhaustion, muscle damage, pro- and anti-inflammatory cytokines, and liver injury in rats after exhaustive exercise. Thirty-two rats were divided into four groups: sedentary control (SC); SC group with FCE supplementation (SC+FCE); exhaustive exercise (E); and E group with FCE supplementation (E+FCE). The SC+FCE and E+FCE groups were treated with gavage administration of 20 mg/kg for seven consecutive days. Blood samples were collected for the evaluation of biochemical parameters. The cytokine levels of TNF-α and IL-10 were also examined. Twenty-four hours after exhaustive exercise, the rat livers were removed for H & E staining. The FCE supplementation could extend the time to exhaustion in exercised rats. The levels of CPK, LDH, AST, ALT, lactate, TNF-α and H & E stains of the liver injury were significantly decreased in the E+FCE group, but the blood glucose and IL-10 were significantly higher in comparison with the E group. This study suggests that FCE supplementation may improve endurance performance and reduce exercise-induced muscle damage, inflammatory stress and liver injury. PMID:23531600

  19. Ethanol consumption and early murine retrovirus infection influence liver, heart, and muscle levels of iron, zinc, and copper in C57BL/6 mice.

    PubMed

    Shahbazian, L M; Wood, S; Watson, R R

    1994-08-01

    The relative and combined roles of ethanol and murine acquired immunodeficiency syndrome (MAIDS) on the mineral status (Fe, Zn, and Cu) of liver (storage site), heart, muscle (nutrient mobile sites) were investigated. C57BL/6 mice were randomly assigned to four groups: (a) uninfected mice fed isocaloric, adequate nutrient diet (NRC), (b) uninfected mice fed the NRC diet with 25% of energy derived from ethanol, (c) LP-BM5 retrovirus-infected mice fed the isocaloric NRC diet, and (d) retrovirus-infected mice fed the NRC diet with 25% of its energy derived from ethanol. The levels of Cu and Zn levels in the liver did not significantly change as a result of ethanol consumption. However hepatic Zn concentration was increased significantly in retrovirus-infected mice. This may be correlated to the increase in their liver weight. Ethanol administration significantly increased Fe concentration in the liver, yet significantly decreased concentration of Cu in the heart. Retrovirus infection alone, which had not proceeded to murine AIDS, resulted in a significant increase in heart Cu and Zn concentration as compared with uninfected mice. Retrovirus infection in C57BL/6 mice significantly increased Fe and Zn level/g of muscle. Early retrovirus infection alters tissue micronutrient levels, and may thus contribute to immunological changes. PMID:7978111

  20. Ectopic lipid storage in non-alcoholic fatty liver disease is not mediated by impaired mitochondrial oxidative capacity in skeletal muscle.

    PubMed

    Cuthbertson, Daniel J; Irwin, Andrew; Sprung, Victoria S; Jones, Helen; Pugh, Christopher J A; Daousi, Christina; Adams, Valerie L; Bimson, William E; Shojaee-Moradie, Fariba; Richardson, Paul; Umpleby, A Margot; Wilding, John P; Kemp, Graham J

    2014-12-01

    Non-alcoholic fatty liver disease (NAFLD), characterized by lipid deposition within the liver [intrahepatocellular lipid (IHCL)], is associated with insulin resistance and the metabolic syndrome (MS). It has been suggested that impaired skeletal muscle mitochondrial function may contribute to ectopic lipid deposition, and the associated MS, by altering post-prandial energy storage. To test this hypothesis, we performed a cross-sectional study of 17 patients with NAFLD [mean±S.D.; age, 45±11 years; body mass index (BMI), 31.6±3.4 kg/m2] and 18 age- and BMI-matched healthy controls (age, 44±11 years; BMI, 30.5±5.2 kg/m2). We determined body composition by MRI, IHCL and intramyocellular (soleus and tibialis anterior) lipids (IMCLs) by proton magnetic resonance spectroscopy (1H-MRS) and skeletal muscle mitochondrial function by dynamic phosphorus magnetic resonance spectroscopy (31P-MRS) of quadriceps muscle. Although matched for BMI and total adiposity, after statistical adjustment for gender, patients with NAFLD (defined by IHCL ≥ 5.5%) had higher IHCLs (25±16% compared with 2±2%; P<0.0005) and a higher prevalence of the MS (76% compared with 28%) compared with healthy controls. Despite this, the visceral fat/subcutaneous fat ratio, IMCLs and muscle mitochondrial function were similar between the NAFLD and control groups, with no significant difference in the rate constants of post-exercise phosphocreatine (PCr) recovery (1.55±0.4 compared with 1.51±0.4 min-1), a measure of muscle mitochondrial function. In conclusion, impaired muscle mitochondrial function does not seem to underlie ectopic lipid deposition, or the accompanying features of the MS, in patients with NAFLD. PMID:24738611

  1. Statin-induced liver injury involves cross-talk between cholesterol and selenoprotein biosynthetic pathways.

    PubMed

    Kromer, Andrea; Moosmann, Bernd

    2009-06-01

    Statins have become the mainstay of hypercholesterolemia treatment. Despite a seemingly clear rationale behind their use, the inhibition of HMG-CoA reductase, these compounds have been shown to elicit a variety of unanticipated and elusive effects and side effects in vivo. Among the most frequently noted side effects of statin treatment are elevations in liver enzymes. Here, we report our finding that atorvastatin, cerivastatin, and lovastatin at clinically common concentrations induce a selective, differential loss of selenoprotein expression in cultured human HepG2 hepatocytes. The primarily affected selenoprotein was glutathione peroxidase (GPx), whose biosynthesis, steady-state expression level, and catalytic activity were significantly reduced with 10 to 100 nM concentrations of the different compounds. Messenger RNA levels of GPx1 and GPx4 were unaffected by statin treatment, pointing at a post-transcriptional mechanism of selenoprotein suppression. Although statins at selenoprotein-modulatory doses were not cytotoxic by themselves, they induced a significantly increased sensitivity of the cells to peroxides, an effect that was largely reversible by supraphysiological concentrations of selenite. We conclude that statins inhibit the expression of inducible selenoproteins by preventing the mevalonate-dependent maturation of the single human selenocysteine-tRNA and may thereby evoke an increased vulnerability of the liver to secondary toxins. Selenoprotein modulation might constitute an important mechanism of statins to bring forth their clinical effects. PMID:19332511

  2. Anti-peptide monoclonal antibody imaging of a common binding domain involved in muscle regulation.

    PubMed Central

    Van Eyk, J. E.; Caday-Malcolm, R. A.; Yu, L.; Irvin, R. T.; Hodges, R. S.

    1995-01-01

    Multiple-component regulatory protein systems function through a generalized mechanism where a single regulatory protein or ligand binds to a variety of receptors to modulate specific functions in a physiologically sensitive context. Muscle contraction is regulated by the interaction of actin with troponin I (TnI) or myosin in a Ca(2+)-sensitive manner. Actin utilizes a single binding domain (residues 1-28) to bind to residues 104-115 of TnI (Van Eyk JE, Sönnichsen FD, Sykes BD, Hodges RS, 1991, In: Rüegg JC, ed, Peptides as probes in muscle research, Heidelberg, Germany: Springer-Verlag, pp 15-31) and to myosin subfragment 1 (S1, an enzymatic fragment of myosin containing both the actin and ATP binding sites) (Van Eyk JE, Hodges RS, 1991, Biochemistry 30:11676-11682) in a Ca(2+)-sensitive manner. We have utilized an anti-TnI peptide (104-115) monoclonal antibody, Mab B4, that binds specifically to TnI, to image the common binding domain of actin and thus mimic the activity of actin including activation of the S1 ATPase activity and TnI-mediated regulation of the S1 ATPase. Mab B4 has also been utilized to identify a receptor binding domain on myosin (residues 633-644) that is recognized by actin. Interestingly, Mab B4 binds to the native protein receptors TnI and S1 with relative affinities of 100- and 25,000-fold higher than the binding affinity to the 12-residue peptide immunogen. Thus, anti-peptide monoclonal antibodies prepared against a receptor binding domain can mimic the ligand binding domain and be utilized as a powerful tool for the detailed analysis of complex multiple-component regulatory systems. PMID:7613476

  3. Integrated analysis of the involvement of nitric oxide synthesis in mitochondrial proliferation, mitochondrial deficiency and apoptosis in skeletal muscle fibres

    PubMed Central

    Rodrigues, Gabriela Silva; Godinho, Rosely Oliveira; Kiyomoto, Beatriz Hitomi; Gamba, Juliana; Oliveira, Acary Souza Bulle; Schmidt, Beny; Tengan, Célia Harumi

    2016-01-01

    Nitric oxide (NO) is an important signaling messenger involved in different mitochondrial processes but only few studies explored the participation of NO in mitochondrial abnormalities found in patients with genetic mitochondrial deficiencies. In this study we verified whether NO synthase (NOS) activity was altered in different types of mitochondrial abnormalities and whether changes in mitochondrial function and NOS activity could be associated with the induction of apoptosis. We performed a quantitative and integrated analysis of NOS activity in individual muscle fibres of patients with mitochondrial diseases, considering mitochondrial function (cytochrome-c-oxidase activity), mitochondrial content, mitochondrial DNA mutation and presence of apoptotic nuclei. Our results indicated that sarcolemmal NOS activity was increased in muscle fibres with mitochondrial proliferation, supporting the relevance of neuronal NOS in the mitochondrial biogenesis process. Sarcoplasmic NOS activity was reduced in cytochrome-c-oxidase deficient fibres, probably as a consequence of the involvement of NO in the regulation of the respiratory chain. Alterations in NOS activity or mitochondrial abnormalities were not predisposing factors to apoptotic nuclei. Taken together, our results show that NO can be considered a potential molecular target for strategies to increase mitochondrial content and indicate that this approach may not be associated with increased apoptotic events. PMID:26856437

  4. Involvement of Interleukin-17A-Induced Hypercontractility of Intestinal Smooth Muscle Cells in Persistent Gut Motor Dysfunction

    PubMed Central

    Akiho, Hirotada; Tokita, Yohei; Nakamura, Kazuhiko; Satoh, Kazuko; Nishiyama, Mitsue; Tsuchiya, Naoko; Tsuchiya, Kazuaki; Ohbuchi, Katsuya; Iwakura, Yoichiro; Ihara, Eikichi; Takayanagi, Ryoichi; Yamamoto, Masahiro

    2014-01-01

    Background and Aim The etiology of post-inflammatory gastrointestinal (GI) motility dysfunction, after resolution of acute symptoms of inflammatory bowel diseases (IBD) and intestinal infection, is largely unknown, however, a possible involvement of T cells is suggested. Methods Using the mouse model of T cell activation-induced enteritis, we investigated whether enhancement of smooth muscle cell (SMC) contraction by interleukin (IL)-17A is involved in postinflammatory GI hypermotility. Results Activation of CD3 induces temporal enteritis with GI hypomotility in the midst of, and hypermotility after resolution of, intestinal inflammation. Prolonged upregulation of IL-17A was prominent and IL-17A injection directly enhanced GI transit and contractility of intestinal strips. Postinflammatory hypermotility was not observed in IL-17A-deficient mice. Incubation of a muscle strip and SMCs with IL-17A in vitro resulted in enhanced contractility with increased phosphorylation of Ser19 in myosin light chain 2 (p-MLC), a surrogate marker as well as a critical mechanistic factor of SMC contractility. Using primary cultured murine and human intestinal SMCs, IκBζ- and p38 mitogen-activated protein kinase (p38MAPK)-mediated downregulation of the regulator of G protein signaling 4 (RGS4), which suppresses muscarinic signaling of contraction by promoting inactivation/desensitization of Gαq/11 protein, has been suggested to be involved in IL-17A-induced hypercontractility. The opposite effect of L-1β was mediated by IκBζ and c-jun N-terminal kinase (JNK) activation. Conclusions We propose and discuss the possible involvement of IL-17A and its downstream signaling cascade in SMCs in diarrheal hypermotility in various GI disorders. PMID:24796324

  5. A Study on Spectrum of Hepatobiliary Dysfunctions and Pattern of Liver Involvement in Dengue Infection

    PubMed Central

    Chattaraj, Sayan; Hajra, Adrija; Mukhopadhyay, Sabyasachi; Ganesan, Vijayan

    2016-01-01

    Introduction The most common arthropod-borne viral (arboviral) disease in humans is dengue. It is transmitted by female Aedes mosquitoes. These mosquitoes are widely distributed in subtropical and tropical areas of the world. Study of dengue infection and its complications are rare from countries like India. Aim In this prospective observational cross-sectional study, we intended to assess the frequency and degree of hepatobiliary dysfunction in adult patients with dengue infection presenting to a tertiary-care medical facility. Materials and Methods The details of all patients with serologically proved dengue fever admitted to a tertiary care hospital in eastern India from July 2014 to June 2015 were prospectively reviewed. We collected data including routine blood count, Liver Function Test (LFT), Prothrombin Time (PT), Activated Partial Prothrombin Time (APTT), abdominal ultrasonography from 110 patients. Results The maximum number of cases were seen in the age group between 46 years and 61 years and of all cases 55.5% were male and 44.5% were female. Pain abdomen and vomiting were the commonest presenting complaints next to fever which was present in all the cases. Elevated liver enzymes, abnormal values of PT and APTT, thrombocytopenia were observed more commonly in Dengue Shock Syndrome (DSS). Gall bladder wall thickening, thrombocytopenia were seen more commonly in both DSS and Dengue Haemorrhagic Fever (DHF). Plasma leakage such as ascites and pleural effusion on USG were seen more frequently in patients with DHF (76.9% and 73.1%) followed by DSS (72% and 68%) and DF (33.9% and 32.2%). Conclusion Hepatobiliary derangement is seen more commonly in severe case of dengue infection. Early recognition of these parameters can also be used as a predictor for assessing the disease severity. PMID:27437266

  6. Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathway.

    PubMed

    Suryawan, Agus; Nguyen, Hanh V; Almonaci, Rosemarie D; Davis, Teresa A

    2012-02-28

    Neonatal growth is characterized by a high protein synthesis rate that is largely due to an enhanced sensitivity to the postprandial rise in insulin and amino acids, especially leucine. The mechanism of leucine's action in vivo is not well understood. In this study, we investigated the effect of leucine infusion on protein synthesis in skeletal muscle and liver of neonatal pigs. To evaluate the mode of action of leucine, we used rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) complex-1 (mTORC1). Overnight-fasted 7-day-old piglets were treated with rapamycin for 1 hour and then infused with leucine (400 μmol·kg(-1)·h(-1)) for 1 hour. Leucine infusion increased the rate of protein synthesis, and ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BP1) phosphorylation in gastrocnemius and masseter muscles (P < 0.05), but not in the liver. The leucine-induced stimulation of protein synthesis and S6K1 and 4E-BP1 phosphorylation were completely blocked by rapamycin, suggesting that leucine action is by an mTORC1-dependent mechanism. Neither leucine nor rapamycin had any effect on the activation of the upstream mTORC1 regulators, AMP-activated protein kinase and protein kinase B, in skeletal muscle or liver. The activation of eIF2α and elongation factor 2 was not affected by leucine or rapamycin, indicating that these two pathways are not limiting steps of leucine-induced protein synthesis. These results suggest that leucine stimulates muscle protein synthesis in neonatal pigs by inducing the activation of mTORC1 and its downstream pathway leading to mRNA translation. PMID:22675606

  7. Therapeutic effect of hybrid training of voluntary and electrical muscle contractions in middle-aged obese women with nonalcoholic fatty liver disease: a pilot trial

    PubMed Central

    Oh, Sechang; Maruyama, Tsuyoshi; Eguchi, Kiyoshi; Shida, Takashi; Arai, Emi; Isobe, Tomonori; Okamoto, Yoshikazu; Shoda, Junichi

    2015-01-01

    Background Exercise training is an effective therapy for nonalcoholic fatty liver disease (NAFLD). Hybrid training (HYB) of voluntary and electrical muscle contractions was developed to prevent disuse atrophy during space flight. HYB can be applied to obtain a strength training effect accompanying articular movement. In this pilot study, we aimed to investigate the therapeutic efficacy of HYB in NAFLD. Methods A total of 15 middle-aged obese women with NAFLD who had no improvement in serum alanine aminotransferase levels and/or liver fat deposition after 12 weeks of lifestyle counseling participated in an HYB program. HYB of the quadriceps and hamstrings was conducted for 20 minutes twice a week for 24 weeks. Results NAFLD patients showed attenuated intramyocellular lipid levels in the quadriceps after the HYB intervention (−15.5%). Levels of leptin (−17.4%), tumor necrosis factor-α (−23.2%), and interleukin-6 (−30.5%) were also decreased after the intervention. HYB led to a significant body weight reduction (−4.7%), which in turn was associated with a significant decrease in serum alanine aminotransferase (−35.8%), gamma-glutamyl transpeptidase (−21.6%), ferritin (−16.0%), oxidative stress (−17.8%) levels, and insulin resistance values (−2.7%). Conclusion In NAFLD, HYB exerts an antiobesity effect and attenuates liver dysfunction and insulin resistance in association with an increase in muscle strength and a decrease in ectopic muscle fat. Therefore, HYB has great potential as a new type of exercise therapy for liver disease in patients with NAFLD. PMID:25767392

  8. Graphene oxide/polyethyleneglycol composite coated stir bar for sorptive extraction of fluoroquinolones from chicken muscle and liver.

    PubMed

    Fan, Wenying; He, Man; Wu, Xiaoran; Chen, Beibei; Hu, Bin

    2015-10-30

    Graphene oxide (GO) is an ideal adsorbent for polar and less polar compounds due to its hexagonal carbon network structure with oxygen-containing groups, while its strong hydrophilicity and water solubility limited its application in sample pretreatment techniques. Herein, GO was composited with polyethyleneglycol (PEG) or polyaniline (PAN) through intermolecular interactions to improve its stability, and the GO/PEG and GO/PAN composite coated stir bars were prepared by sol-gel technique. Compared with GO/PAN composite and polydimethylsiloxane (PDMS) coated stir bar, the prepared GO/PEG composite coated stir bar exhibited higher extraction efficiency for five fluoroquinolones (FQs). Based on it, a method of GO/PEG composite coated stir bar sorptive extraction (SBSE) combined with high-performance liquid chromatography-fluorescence detector (HPLC-FLD) was proposed. The factors influencing SBSE, such as sample pH, salt effect, stirring rate, extraction time, desorption solvent and desorption time, were optimized, and the analytical performance of the developed SBSE-HPLC-FLD method was evaluated. The limits of detection (LODs) for five FQs were in the range of 0.0045-0.0079μgL(-1), and the enrichment factors (EFs) were in the range of 41.5-65.5-fold (theoretical enrichment factor was 100-fold). The reproducibility was also investigated at concentrations of 0.05μgL(-1) and the relative standard deviations (RSDs, n=6) were found to be in the range of 4.6-12.1%. The proposed method was successfully applied for the determination of FQs in chicken muscle and chicken liver samples. PMID:26433263

  9. AMPK, a metabolic sensor, is involved in isoeugenol-induced glucose uptake in muscle cells

    PubMed Central

    Kim, Nami; Lee, Jung Ok; Lee, Hye Jeong; Lee, Yong Woo; Kim, Hyung Ip; Kim, Su Jin; Park, Sun Hwa; Lee, Chul Su; Ryoo, Sun Woo; Hwang, Geum-Sook; Kim, Hyeon Soo

    2016-01-01

    Isoeugenol exerts various beneficial effects on human health. However, the mechanisms underlying these effects are poorly understood. In this study, we observed that isoeugenol activated AMP-activated protein kinase (AMPK) and increased glucose uptake in rat L6 myotubes. Isoeugenol-induced increase in intracellular calcium concentration and glucose uptake was inhibited by STO-609, an inhibitor of calcium/calmodulin-dependent protein kinase kinase (CaMKK). Isoeugenol also increased the phosphorylation of protein kinase C-α (PKCα). Chelation of calcium with BAPTA-AM blocked isoeugenol-induced AMPK phosphorylation and glucose uptake. Isoeugenol stimulated p38MAPK phosphorylation that was inhibited after pretreatment with compound C, an AMPK inhibitor. Isoeugenol also increased glucose transporter type 4 (GLUT4) expression and its translocation to the plasma membrane. GLUT4 translocation was not observed after the inhibition of AMPK and CaMKK. In addition, isoeugenol activated the Akt substrate 160 (AS160) pathway, which is downstream of the p38MAPK pathway. Knockdown of the gene encoding AS160 inhibited isoeugenol-induced glucose uptake. Together, these results indicate that isoeugenol exerts beneficial health effects by activating the AMPK/p38MAPK/AS160 pathways in skeletal muscle. PMID:26585419

  10. Dietary methionine availability affects the main factors involved in muscle protein turnover in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Belghit, Ikram; Skiba-Cassy, Sandrine; Geurden, Inge; Dias, Karine; Surget, Anne; Kaushik, Sadasivam; Panserat, Stéphane; Seiliez, Iban

    2014-08-28

    Methionine is a limiting essential amino acid in most plant-based ingredients of fish feed. In the present study, we aimed to determine the effect of dietary methionine concentrations on several main factors involved in the regulation of mRNA translation and the two major proteolytic pathways (ubiquitin-proteasome and autophagy-lysosomal) in the white muscle of rainbow trout (Oncorhynchus mykiss). The fish were fed for 6 weeks one of the three isonitrogenous diets providing three different methionine concentrations (deficient (DEF), adequate (ADQ) and excess (EXC)). At the end of the experiment, the fish fed the DEF diet had a significantly lower body weight and feed efficiency compared with those fed the EXC and ADQ diets. This reduction in the growth of fish fed the DEF diet was accompanied by a decrease in the activation of the translation initiation factors ribosomal protein S6 and eIF2α. The levels of the main autophagy-related markers (LC3-II and beclin 1) as well as the expression of several autophagy genes (atg4b, atg12 l, Uvrag, SQSTM1, Mul1 and Bnip3) were higher in the white muscle of fish fed the DEF diet. Similarly, the mRNA levels of several proteasome-related genes (Fbx32, MuRF2, MuRF3, ZNF216 and Trim32) were significantly up-regulated by methionine limitation. Together, these results extend our understanding of mechanisms regulating the reduction of muscle growth induced by dietary methionine deficiency, providing valuable information on the biomarkers of the effects of low-fishmeal diets. PMID:24877663

  11. Effect of Inorganic Dietary Selenium Supplementation on Selenoprotein and Lipid Metabolism Gene Expression Patterns in Liver and Loin Muscle of Growing Lambs.

    PubMed

    Juszczuk-Kubiak, Edyta; Bujko, Kamila; Cymer, Monika; Wicińska, Krystyna; Gabryszuk, Mirosław; Pierzchała, Mariusz

    2016-08-01

    Effect of selenium (Se) supplementation on the selenoprotein and lipid metabolism gene expression patterns in ruminants, especially in lambs is not yet fully understood. The aim of study was to evaluate the effect of Se supplementation on the messenger RNA (mRNA) expression patterns of selected selenoproteins and genes related to lipid metabolism in growing lambs. The experiment was conducted on 48 Polish Merino lambs divided into two groups (n = 24): control (C)-lambs fed with a basal diet (BD) with no Se supplementation, and supplemented (S)-lambs fed with a BD, supplemented with 0.5 mg Se/kg as sodium selenate for 8 weeks. Expression of 12 selenoproteins and six genes related to lipid metabolism was analyzed in the liver and longissimus dorsi (LD) muscle of growing lambs by qPCR. Significant differences were found in the expression of GPX1, GPX2, SEPM, SEPW1, SEP15, SEPGS2, and TXNRD1 in the liver, and GPX1, SEPP1, SEPN1, SEPW1, SEP15, and MSRB1 in the LD muscle between S and C lambs. Se supplementation mainly upregulated SEPW1, SEP15 (P < 0.001; P < 0.01) mRNA expression in the liver, and GPX1, SEPP1, SEPN1, SEPW1 (P < 0.001; P < 0.01) in the muscle of S group. On the other hand, significant decrease in GPX2 (P < 0.01), SEPM (P < 0.001), and SEPHS2 (P < 0.01) mRNA expression levels were observed in the liver of S group of lambs. Se supplementation did not affect PON1, LXRα, and PPARα mRNA expression levels, but a significant increase in mRNA levels of APOE and LPL in the LD muscle (P < 0.05) as well as LPL (P < 0.05) in the liver were noticed in the group of Se supplemented lambs. Our study confirmed that, in lambs, similarly to other species, mRNA expression patterns of several selenoproteins highly depend on dietary Se levels, and their expression is ruled by hierarchical principles and tissue-specific mechanisms. Moreover, the study showed that changes Se intake leads to different levels of genes expression related

  12. Bioaccumulation of mercury, cadmium, zinc, chromium, and lead in muscle, liver, and spleen tissues of a large commercially valuable catfish species from Brazil.

    PubMed

    Arantes, Fábio P; Savassi, Lourenço A; Santos, Hélio B; Gomes, Marcos V T; Bazzoli, Nilo

    2016-03-01

    The increasing amounts of heavy metals entering aquatic environments can result in high accumulation levels of these contaminants in fish and their consumers, which pose a serious risk to ecosystems and human health. We investigated the concentrations of mercury (Hg), cadmium (Cd), zinc (Zn), chromium (Cr), and lead (Pb) in muscle, liver, and spleen tissues of Pseudoplatystoma corruscans specimens collected from two sites on the Paraopeba River, Brazil. The level of heavy metals concentrations in the tissues was often higher in viscera (i.e. liver and spleen) than in muscle, and thus, the viscera should not be considered for human consumption. Correlations between metal concentrations and fish size were not significant. Although the levels of muscle bioaccumulation of Hg, Cd, Zn, Cr, and Pb, generally do not exceed the safe levels for human consumption, the constant presence of heavy metals in concentrations near those limits considered safe for human consumption, is a reason for concern, and populations who constantly consume fish from polluted rivers should be warned. Our findings also indicate that in a river network where certain areas are connected to other areas with high rates of environmental pollutants, people should be cautious about the regular consumption of fish, even when the fish consumed are caught in stretches of the basin where contamination levels are considered low, since many of the freshwater fish with high commercial value, such as the catfish surubim, are migratory. PMID:26871492

  13. Effects of a Diet Enriched with Polyunsaturated, Saturated, or Trans Fatty Acids on Cytokine Content in the Liver, White Adipose Tissue, and Skeletal Muscle of Adult Mice

    PubMed Central

    dos Santos, Bruno; Estadella, Debora; Hachul, Ana Cláudia Losinskas; Okuda, Marcos Hiromu; Moreno, Mayara Franzoi; Oyama, Lila Missae; Ribeiro, Eliane Beraldi; Oller do Nascimento, Claudia Maria da Penha

    2013-01-01

    This study analyzed the effect of diet enriched with 30% lipids on cytokines content in different tissues. Swiss male mice were distributed into four groups treated for 8 weeks with control (C, normolipidic diet); soybean oil (S); lard (L); and hydrogenated vegetable fat (H). We observed an increase in carcass fat in groups S and L, and the total amount of fatty deposits was only higher in group L compared with C group. The serum levels of free fatty acids were lower in the L group, and insulin, adiponectin, lipid profile, and glucose levels were similar among the groups. IL-10 was lower in group L in mesenteric and retroperitoneal adipose tissues. H reduced IL-10 only in retroperitoneal adipose tissue. There was an increase in IL-6 in the gastrocnemius muscle of the L group, and a positive correlation between TNF-α and IL-10 was observed in the livers of groups C, L, and H and in the muscles of all groups studied. The results suggested relationships between the quantity and quality of lipids ingested with adiposity, the concentration of free fatty acids, and cytokine production in white adipose tissue, gastrocnemius muscle, and liver. PMID:24027356

  14. Spatial and seasonal variations of trace elements concentrations in liver and muscle of round Sardinelle (Sardinella aurita) and Senegalese sole (Solea senegalensis) along the Senegalese coast.

    PubMed

    Diop, Mamadou; Howsam, Michael; Diop, Cheikh; Cazier, Fabrice; Goossens, Jean F; Diouf, Amadou; Amara, Rachid

    2016-02-01

    Concentrations of 11 elements (As, Cd, Cr, Cu, Fe, Mn, Ni, Pb, Se,V and Zn) were quantified in liver and muscle from two commercially important fish species from the Senegalese coast. The fish, a small pelagic species (the round sardinella) and a benthic species (the Senegalese sole) were collected from five sites during the dry and wet seasons in 2013. For both species, elements were more concentrated in liver than in muscle. There was no clear seasonal pattern in concentration of elements, however inter-site differences were observed. We found significant differences in element concentrations between the two studied species, likely associated with their behavior, feeding and habitat use. The concentrations of Cd, Fe, and Pb were significantly higher in sardinella whereas concentration of As, Cu, Cr, Mn and Se were highest in sole. The concentration of cadmium was particularly high in the liver of sardinella (from 0.9 to 56 mg kg(-1), with a mean ± sd of 17.2 ± 11.5 mg kg(-1)) and may be related to anthropogenic pressure such as the phosphate industry but also to the upwelling current which brings dissolved elements to the surface that are taken up by plankton. The results showed that concentrations of Cd and Pb were below the limit values established by the European Community and pose no threat to public health. PMID:26410572

  15. Circulating ghrelin and leptin concentrations and growth hormone secretagogue receptor abundance in liver, muscle, and adipose tissue of beef cattle exhibiting differences in composition of gain.

    PubMed

    Jennings, J S; Wertz-Lutz, A E; Pritchard, R H; Weaver, A D; Keisler, D H; Bruns, K

    2011-12-01

    Data from species other than cattle indicate that ghrelin and GH secretagogue receptor (GHS-R) could play a key role in fat deposition, energy homeostasis, or glucose metabolism by directly affecting liver and adipose tissue metabolism. Beef steers (n = 72) were used to test the hypothesis that plasma ghrelin and leptin concentrations and abundance of the GHS-R in liver, muscle, and adipose tissues differ in steers exhibiting differences in composition of gain. At trial initiation (d 0), 8 steers were slaughtered for initial carcass composition. The remaining 64 steers were stratified by BW, allotted to pen, and treatment was assigned randomly to pen. Steers were not implanted with anabolic steroids. Treatments were 1) a low-energy (LE) diet fed during the growing period (0 to 111 d) followed by a high-energy (HE) diet during the finishing period (112 to 209 d; LE-HE) or 2) the HE diet for the duration of the trial (1 to 209 d; HE-HE). Eight steers per treatment were slaughtered on d 88, 111, 160, and 209. Carcass ninth, tenth, and eleventh rib sections were dissected for chemical composition and regression equations were developed to predict compositional gain. Liver, muscle, and subcutaneous adipose tissues were frozen in liquid nitrogen for subsequent Western blotting for GHS-R. Replicate blood samples collected before each slaughter were assayed for ghrelin and leptin concentrations. When compared at a common compositional fat end-point, the rate of carcass fat accretion (g·kg of shrunk BW(-1)) was greater (P < 0.001) in HE-HE steers whereas the rate of carcass protein accretion (g·kg of shrunk BW(-1)) was less (P < 0.001) compared with LE-HE steers. When compared at a common compositional fat end-point, plasma leptin, ghrelin, and insulin concentrations were greater (P < 0.05) for HE-HE compared with LE-HE steers. Abundance of the GHS-R, to which ghrelin binds, increased over time in liver and adipose tissue but did not differ as a result of treatment

  16. Melatonin Mediates Monochromatic Light-induced Insulin-like Growth Factor 1 Secretion of Chick Liver: Involvement of Membrane Receptors.

    PubMed

    Li, Suqi; Cao, Jing; Wang, Zixu; Dong, Yulan; Wang, Wenli; Chen, Yaoxing

    2016-07-01

    Monochromatic lights influenced the proliferation and differentiation of skeletal satellite cells in broilers by the enhancement of insulin-like growth factor 1 (IGF-1) secretion. However, whether melatonin (MEL)-mediated monochromatic lights influenced the IGF-1 secretion remains unclear. Newly hatched broilers, including intact, sham operation and pinealectomy groups, were exposed to blue (BL), green (GL), red (RL) and white light (WL) from a light-emitting diode system for 14 days. The results showed that GL effectively promoted the secretion of MEL and IGF-1, the expression of proliferating cell nuclear antigen and MEL receptor subtypes Mel1a, Mel1b and Mel1c in the liver compared to BL and RL in vivo. Moreover, those was a positive correlation between MEL and IGF-1 (r = 0.834). After pinealectomy, however, these parameters declined, and there were no differences between GL and other monochromatic light treatments. In vitro, exogenous MEL increased hepatocyte proliferation and IGF-1 secretion. Meanwhile, the MEL enhancements were suppressed by prazosin (selective Mel1c antagonist), followed by luzindole (nonselective Mel1a/Mel1b antagonist), but not suppressed by 4-phenyl-2-propionamideotetralin (selective Mel1b antagonist). These findings demonstrated that MEL mediated the monochromatic light-induced secretion of IGF-1 in chicks' livers by Mel1c and that Mel1a may be involved in this process. PMID:27128575

  17. Long-chain acyl-CoA synthetase in fatty acid metabolism involved in liver and other diseases: An update

    PubMed Central

    Yan, Sheng; Yang, Xue-Feng; Liu, Hao-Lei; Fu, Nian; Ouyang, Yan; Qing, Kai

    2015-01-01

    Long-chain acyl-CoA synthetase (ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer membrance catalyze fatty acids with chain lengths from 12 to 20 carbon atoms to form acyl-CoAs, which are lipid metabolic intermediates and involved in fatty acid metabolism, membrane modifications and various physiological processes. Gain- or loss-of-function studies have shown that the expression of individual ACSL isoforms can alter the distribution and amount of intracellular fatty acids. Changes in the types and amounts of fatty acids, in turn, can alter the expression of intracellular ACSLs. ACSL family members affect not only the proliferation of normal cells, but the proliferation of malignant tumor cells. They also regulate cell apoptosis through different signaling pathways and molecular mechanisms. ACSL members have individual functions in fatty acid metabolism in different types of cells depending on substrate preferences, subcellular location and tissue specificity, thus contributing to liver diseases and metabolic diseases, such as fatty liver disease, obesity, atherosclerosis and diabetes. They are also linked to neurological disorders and other diseases. However, the mechanisms are unclear. This review addresses new findings in the classification and properties of ACSLs and the fatty acid metabolism-associated effects of ACSLs in diseases. PMID:25834313

  18. Cholinergic activation of the murine trachealis muscle via non-vesicular acetylcholine release involving low-affinity choline transporters.

    PubMed

    Nassenstein, Christina; Wiegand, Silke; Lips, Katrin S; Li, Guanfeng; Klein, Jochen; Kummer, Wolfgang

    2015-11-01

    In addition to quantal, vesicular release of acetylcholine (ACh), there is also non-quantal release at the motor endplate which is insufficient to evoke postsynaptic responses unless acetylcholinesterase (AChE) is inhibited. We here addressed potential non-quantal release in the mouse trachea by organ bath experiments and (immuno)histochemical methods. Electrical field stimulation (EFS) of nerve terminals elicited tracheal constriction that is largely due to ACh release. Classical enzyme histochemistry demonstrated acetylcholinesterase (AChE) activity in nerve fibers in the muscle and butyrylcholinesterase (BChE) activity in the smooth muscle cells. Acute inhibition of both esterases by eserine significantly raised tracheal tone which was fully sensitive to atropine. This effect was reduced, but not abolished, in AChE, but not in BChE gene-deficient mice. The eserine-induced increase in tracheal tone was unaffected by vesamicol (10(-5)M), an inhibitor of the vesicular acetylcholine transporter, and by corticosterone (10(-4)M), an inhibitor of organic cation transporters. Hemicholinium-3, in low concentrations an inhibitor of the high-affinity choline transporter-1 (CHT1), completely abrogated the eserine effects when applied in high concentrations (10(-4)M) pointing towards an involvement of low-affinity choline transporters. To evaluate the cellular sources of non-quantal ACh release in the trachea, expression of low-affinity choline transporter-like family (CTL1-5) was evaluated by RT-PCR analysis. Even though these transporters were largely abundant in the epithelium, denudation of airway epithelial cells had no effect on eserine-induced tracheal contraction, indicating a non-quantal release of ACh from non-epithelial sources in the airways. These data provide evidence for an epithelium-independent non-vesicular, non-quantal ACh release in the mouse trachea involving low-affinity choline transporters. PMID:26278668

  19. Leucine alleviates dexamethasone-induced suppression of muscle protein synthesis via synergy involvement of mTOR and AMPK pathways.

    PubMed

    Wang, Xiao J; Yang, Xin; Wang, Ru X; Jiao, Hong C; Zhao, Jing P; Song, Zhi G; Lin, Hai

    2016-07-01

    Glucocorticoids (GCs) are negative muscle protein regulators that contribute to the whole-body catabolic state during stress. Mammalian target of rapamycin (mTOR)-signalling pathway, which acts as a central regulator of protein metabolism, can be activated by branched-chain amino acids (BCAA). In the present study, the effect of leucine on the suppression of protein synthesis induced by GCs and the pathway involved were investigated. In vitro experiments were conducted using cultured C2C12 myoblasts to study the effect of GCs on protein synthesis, and the involvement of mTOR pathway was investigated as well. After exposure to dexamethasone (DEX, 100 μmol/l) for 24 h, protein synthesis in muscle cells was significantly suppressed (P<0.05), the phosphorylations of mTOR, ribosomal protein S6 protein kinase 1 (p70s6k1) and eukaryotic initiation factor 4E binding protein 1 (4EBP1) were significantly reduced (P<0.05). Leucine supplementation (5 mmol/l, 10 mmol/l and 15 mmol/l) for 1 h alleviated the suppression of protein synthesis induced by DEX (P<0.05) and was accompanied with the increased phosphorylation of mTOR and decreased phosphorylation of AMPK (P<0.05). Branched-chain amino transferase 2 (BCAT2) mRNA level was not influenced by DEX (P>0.05) but was increased by leucine supplementation at a dose of 5 mmol/l (P<0.05). PMID:27129299

  20. Chronic subordination stress selectively downregulates the insulin signaling pathway in liver and skeletal muscle but not in adipose tissue of male mice

    PubMed Central

    Sanghez, Valentina; Cubuk, Cankut; Sebastián-Leon, Patricia; Carobbio, Stefania; Dopazo, Joaquin; Vidal-Puig, Antonio; Bartolomucci, Alessandro

    2016-01-01

    Abstract Chronic stress has been associated with obesity, glucose intolerance, and insulin resistance. We developed a model of chronic psychosocial stress (CPS) in which subordinate mice are vulnerable to obesity and the metabolic-like syndrome while dominant mice exhibit a healthy metabolic phenotype. Here we tested the hypothesis that the metabolic difference between subordinate and dominant mice is associated with changes in functional pathways relevant for insulin sensitivity, glucose and lipid homeostasis. Male mice were exposed to CPS for four weeks and fed either a standard diet or a high-fat diet (HFD). We first measured, by real-time PCR candidate genes, in the liver, skeletal muscle, and the perigonadal white adipose tissue (pWAT). Subsequently, we used a probabilistic analysis approach to analyze different ways in which signals can be transmitted across the pathways in each tissue. Results showed that subordinate mice displayed a drastic downregulation of the insulin pathway in liver and muscle, indicative of insulin resistance, already on standard diet. Conversely, pWAT showed molecular changes suggestive of facilitated fat deposition in an otherwise insulin-sensitive tissue. The molecular changes in subordinate mice fed a standard diet were greater compared to HFD-fed controls. Finally, dominant mice maintained a substantially normal metabolic and molecular phenotype even when fed a HFD. Overall, our data demonstrate that subordination stress is a potent stimulus for the downregulation of the insulin signaling pathway in liver and muscle and a major risk factor for the development of obesity, insulin resistance, and type 2 diabetes mellitus. PMID:26946982

  1. Dietary L-carnitine supplementation increases lipid deposition in the liver and muscle of yellow catfish (Pelteobagrus fulvidraco) through changes in lipid metabolism.

    PubMed

    Zheng, Jia-Lang; Luo, Zhi; Zhuo, Mei-Qing; Pan, Ya-Xiong; Song, Yu-Feng; Hu, Wei; Chen, Qi-Liang

    2014-09-14

    Carnitine has been reported to improve growth performance and reduce body lipid content in fish. Thus, we hypothesised that carnitine supplementation can improve growth performance and reduce lipid content in the liver and muscle of yellow catfish (Pelteobagrus fulvidraco), a commonly cultured freshwater fish in inland China, and tested this hypothesis in the present study. Diets containing l-carnitine at three different concentrations of 47 mg/kg (control, without extra carnitine addition), 331 mg/kg (low carnitine) and 3495 mg/kg (high carnitine) diet were fed to yellow catfish for 8 weeks. The low-carnitine diet significantly improved weight gain (WG) and reduced the feed conversion ratio (FCR). In contrast, the high-carnitine diet did not affect WG and FCR. Compared with the control diet, the low-carnitine and high-carnitine diets increased lipid and carnitine contents in the liver and muscle. The increased lipid content in the liver could be attributed to the up-regulation of the mRNA levels of SREBP, PPARγ, fatty acid synthase (FAS) and ACCa and the increased activities of lipogenic enzymes (such as FAS, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and malic enzyme) and to the down-regulation of the mRNA levels of the lipolytic gene CPT1A. The increased lipid content in muscle could be attributed to the down-regulation of the mRNA levels of the lipolytic genes CPT1A and ATGL and the increased activity of lipoprotein lipase. In conclusion, in contrast to our hypothesis, dietary carnitine supplementation increased body lipid content in yellow catfish. PMID:24933091

  2. Concentrations of trace elements in the kidney, liver, muscle, and skin of short sea snake (Lapemis curtus) from the Strait of Hormuz Persian Gulf.

    PubMed

    Heydari Sereshk, Zahra; Riyahi Bakhtiari, Alireza

    2015-10-01

    To our knowledge, this is the first report into trace elements accumulation in tissues of the short sea snake (Lapemis curtus). Lead (Pb), cadmium (Cd), copper (Cu), vanadium (V), nickel (Ni), and zinc (Zn) were determined in the kidney, liver, skin, and muscle tissues of short sea snake, L. curtus, from the Strait of Hormuz during October 2011. Skins generally displayed the lowest trace element burdens. Kidneys displayed the highest Pb, Cd, V, Ni, and Cu mean concentrations (0.89, 0.04, 1.66, 6.22, and 20.23 μg g(-1) dry weight, respectively), while muscle exhibited the highest Zn levels (493.32 μg g(-1) dry weight). Concentration ranges of the selected trace elements were compared with those reported in other studies. Data presented here may be considered as a baseline for further ecotoxicological studies in sea snakes. PMID:26036580

  3. Determination of monensin, salinomycin and narasin in muscle, liver and eggs from domestic fowl using liquid chromatography-electrospray mass spectrometry.

    PubMed

    Blanchflower, W J; Kennedy, D G

    1996-01-26

    A method is presented for the simultaneous determination of the three ionophores, monensin, salinomycin and narasin in muscle, liver and eggs from domestic fowl. Samples are homogenised in methanol and any ionophores present are extracted into toluene-hexane. The extracts are concentrated and injected into a bench-top electrospray LC-MS system. Chromatography is carried out using an end-capped reversed-phase column, with a mobile phase consisting a mixture of acetonitrile, methanol, tetrahydrofuran, trifluoroacetic acid and water. Using single-ion monitoring, the ionophores can be detected down to the 1 ng/g level. PMID:8852709

  4. Evaluating the effect of 20-hydroxyecdysone (20HE) on mechanistic target of rapamycin complex 1 (mTORC1) signaling in the skeletal muscle and liver of rats.

    PubMed

    Anthony, Tracy G; Mirek, Emily T; Bargoud, Albert Raouf; Phillipson-Weiner, Lindsey; DeOliveira, Christopher M; Wetstein, Berish; Graf, Brittany L; Kuhn, Peter E; Raskin, Ilya

    2015-12-01

    Phytoecdysteroids such as 20-hydroxyecdysone (20HE) are nutritional supplements marketed as enhancers of lean body mass. In this study the impact of 20HE ingestion on protein kinase B/Akt-mechanistic target of rapamycin complex 1 signaling in the skeletal muscle and liver of male rats was found to be limited. Bioavailability of 20HE, whether consumed alone or with leucine, also remained low at all doses ingested. Additional work is necessary to clarify 20HE mechanism of action in vivo. PMID:26584207

  5. Simultaneous determination of perfluorinated compounds and their potential precursors in mussel tissue and fish muscle tissue and liver samples by liquid chromatography-electrospray-tandem mass spectrometry.

    PubMed

    Zabaleta, I; Bizkarguenaga, E; Prieto, A; Ortiz-Zarragoitia, M; Fernández, L A; Zuloaga, O

    2015-03-27

    An analytical method for the simultaneous determination in fish liver and muscle tissue and mussel samples of 14 perfluorinated compounds (PFCs), including three perfluoroalkylsulfonates (PFSAs), seven perfluorocarboxylic acids (PFCAs), three perfluorophosphonic acids (PFPAs) and perfluorooctanesulfonamide (PFOSA), and 10 potential precursors, including four polyfluoroalkyl phosphates (PAPs), four fluorotelomer saturated acids (FTCAs) and two fluorotelomer unsaturated acids (FTUCAs), was developed in the present work. Different clean-up strategies by means of solid-phase extraction (SPE) using a mix-mode weak anion exchanger (WAX), reverse phase Envi-Carb or a combination of them was optimized and evaluated for the clean-up of focused ultrasonic solid-liquid (FUSLE) extracts before the analysis by liquid chromatography-triple quadrupole tandem mass spectrometry (LC-MS/MS). Mix-mode WAX coupled in-line to Envi-Carb was finally selected since it rendered the cleanest extracts and minimum matrix effect. The FUSLE-SPE-LC-MS/MS methodology was validated in terms of recovery, precision and method detection limits (MDLs). Apparent recovery values in the 65-116%, 59-119% and 67-126% range and MDLs in the 0.1-2.7 ng/g, 0.1-3.8 ng/g and 0.2-3.1ng/g range were obtained for liver, mussel and fish muscle tissue samples, respectively. The method developed was applied to the analysis of grey mullet liver (Chelon labrosus) and mussel (Mytilus galloprovincialis) samples from the Basque Coast (North of Spain) and Yellowfin tuna muscle tissue (Thunnus albacares) samples from the Indian Ocean. To the best of our knowledge this is the first method that describes the simultaneous determination of 14 PFCs and 10 potential precursors in fish liver, fish muscle tissue and mussel samples. Besides, this is the first time that 8:2 monosubstituted polyfluorodecyl phosphate (8:2 monoPAP) and 8:2 disubstituted polyfluorodecyl phosphate (8:2 diPAP) were detected in mussel and tuna samples

  6. Metabolic compensations in mitochondria isolated from the heart, liver, kidney, brain and white muscle in the southern catfish (Silurus meridionalis) by seasonal acclimation.

    PubMed

    Yan, Yulian; Xie, Xiaojun

    2015-05-01

    In order to examine the effects of seasonal acclimation on mitochondrial metabolic functions and test tissue-specific pattern of the metabolic compensation within individuals of the southern catfish (Silurus meridionalis Chen), rates of mitochondrial respiration and activities of cytochrome c oxidase (COX) in the heart, liver, kidney, brain and white muscle of this fish in the summer-acclimatized group (153.20±1.66 g) and winter-acclimatized group (177.71±3.04 g) were measured at seven assay temperatures (7.5, 12.5, 17.5, 22.5, 27.5, 32.5 and 37.5°C), respectively. The results show that compensatory adjustments in state III respiratory rate and COX activity occur significantly in the heart, kidney and liver, but do not in the brain and white muscle, which suggest that the metabolic compensation of this fish in response to seasonal acclimation exhibits a tissue-specific pattern. The cold acclimation increases mitochondrial oxidative capacities in the heart, kidney and liver concomitantly with reducing their upper thermal limits of mitochondrial functions at acute warming and the thermal tolerance shifts in the same tissue-specific pattern as the metabolic compensation. When combining the effects of seasonal acclimation on mitochondrial oxidative capacity and organ mass, the metabolic compensation demonstrates an organ-specific pattern with four categories: over-compensation in the heart, complete compensation in the kidney, partial compensation in the liver and no compensation in the brain. The organ-specific pattern of metabolic compensation might be a trade-off strategy of the performance adjustments in the seasonal acclimation for this fish to maximize its fitness. PMID:25498350

  7. Sources of calretinin inputs to motoneurons of extraocular muscles involved in upgaze

    PubMed Central

    Ahlfeld, Julia; Mustari, Michael; Horn, Anja K.E.

    2015-01-01

    Recent monkey studies showed that motoneurons of the oculomotor nucleus involved in upward eye movements receive a selective input from afferents containing calretinin (CR). Here, we investigated the sources of these CR-positive afferents. After injections of tract-tracers into the oculomotor nucleus (nIII) of two monkeys, the retrograde labeling was combined with CR-immunofluorescence in frozen brainstem sections. Three sources of CR inputs to nIII were found: the rostral interstitial nucleus of the medial longitudinal fascicle (RIMLF), the interstitial nucleus of Cajal, and the y-group. CR is not present in all premotor upward-moving pathways. The excitatory secondary vestibulo-ocular neurons in the magnocellular part of the medial vestibular nuclei contained nonphosphorylated neurofilaments, but no CR, and they received a strong supply of large CR-positive boutons. In conclusion, the present study presents evidence that only specific premotor pathways for upward eye movements—excitatory upgaze pathways—contain CR, but not the up vestibulo-ocular reflex pathways. This property may help to differentiate between premotor up- and downgaze pathways in correlative clinico-anatomical studies in humans. PMID:21950981

  8. Polyunsaturated fatty acid biosynthesis is involved in phenylephrine-mediated calcium release in vascular smooth muscle cells.

    PubMed

    Irvine, Nicola A; Lillycrop, Karen A; Fielding, Barbara; Torrens, Christopher; Hanson, Mark A; Burdge, Graham C

    2015-10-01

    Stimulation of vascular smooth muscle (VSM) α1-adrenoceptors induces myosin phosphorylation and vasoconstriction via mobilisation of intracellular calcium and production of specific eicosanoids. Polyunsaturated fatty acid (PUFA) biosynthesis in VSM cells is involved, although the precise mechanism is not known. To address this, we characterised PUFA biosynthesis in VSM cells and determined its role in intracellular calcium release and eicosanoid production. Murine VSM cells converted 18:2n-6 to longer chain PUFA including 22:5n-6. Δ6 (D6d) and Δ5 (D5d) desaturase, and elongase (Elovl) 5 were expressed. Elovl2 was not detected in human, mouse or rat VSM cells, or in rat or mouse aortae, but tit was not associated with hypermethylation of its promoter. D6d or D5d inhibition reduced 18:3n-6 and 20:4n-6 synthesis, respectively, and induced concentration-related decrease in phenylephrine-mediated calcium release, and in PGE2 and PGF2α secretion. Together these findings suggest that PUFA biosynthesis in VSM cells is involved in calcium release associated with vasoconstriction. PMID:26324193

  9. Elevated expression of protein biosynthesis genes in liver and muscle of hibernating black bears (Ursus americanus) Address for reprint requests and other correspondence: V. B. Fedorov, Inst. of Arctic Biology, Univ. of Alaska Fairbanks, Fairbanks, AK 99775 (e-mail: fnvf@uaf.edu). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    PubMed Central

    Fedorov, Vadim B.; Goropashnaya, Anna V.; Tøien, Øivind; Stewart, Nathan C.; Gracey, Andrew Y.; Chang, Celia; Qin, Shizhen; Pertea, Geo; Quackenbush, John; Showe, Louise C.; Showe, Michael K.; Boyer, Bert B.; Barnes, Brian M.

    2009-01-01

    We conducted a large-scale gene expression screen using the 3,200 cDNA probe microarray developed specifically for Ursus americanus to detect expression differences in liver and skeletal muscle that occur during winter hibernation compared with animals sampled during summer. The expression of 12 genes, including RNA binding protein motif 3 (Rbm3), that are mostly involved in protein biosynthesis, was induced during hibernation in both liver and muscle. The Gene Ontology and Gene Set Enrichment analysis consistently showed a highly significant enrichment of the protein biosynthesis category by overexpressed genes in both liver and skeletal muscle during hibernation. Coordinated induction in transcriptional level of genes involved in protein biosynthesis is a distinctive feature of the transcriptome in hibernating black bears. This finding implies induction of translation and suggests an adaptive mechanism that contributes to a unique ability to reduce muscle atrophy over prolonged periods of immobility during hibernation. Comparing expression profiles in bears to small mammalian hibernators shows a general trend during hibernation of transcriptional changes that include induction of genes involved in lipid metabolism and carbohydrate synthesis as well as depression of genes involved in the urea cycle and detoxification function in liver. PMID:19240299

  10. Mode of action analysis for pesticide-induced rodent liver tumours involving activation of the constitutive androstane receptor: relevance to human cancer risk.

    PubMed

    Lake, Brian G; Price, Roger J; Osimitz, Thomas G

    2015-06-01

    A number of non-genotoxic chemicals, including some pesticides, have been shown to increase the incidence of liver tumours in rats and/or mice. Frameworks for analysing the modes of action (MOAs) by which chemicals produce liver tumours in rodents and the relevance of such tumour data for human risk assessment have now been established. One common MOA for rodent liver tumour formation by non-genotoxic chemicals involves activation of the constitutive androstane receptor (CAR). Key and associative events for a CAR-activation MOA include receptor activation, liver hypertrophy, induction of cytochrome P450 enzyme activities, increased replicative DNA synthesis, altered hepatic foci and liver tumours. While some effects of rodent CAR activators can be observed in human liver, a major species difference is that, unlike rodents, CAR activators do not increase replicative DNA synthesis in human hepatocytes. The CAR-activation MOA for rodent liver tumour formation is thus not plausible for humans, and hence such compounds do not pose a hepatocarcinogenic hazard for humans. PMID:25045103

  11. Characterization of human liver enzymes involved in the biotransformation of boceprevir, a hepatitis C virus protease inhibitor.

    PubMed

    Ghosal, Anima; Yuan, Yuan; Tong, Wei; Su, Ai-Duen; Gu, Chunyan; Chowdhury, Swapan K; Kishnani, Narendra S; Alton, Kevin B

    2011-03-01

    Boceprevir (SCH 503034), a protease inhibitor, is under clinical development for the treatment of human hepatitis C virus infections. In human liver microsomes, formation of oxidative metabolites after incubations with [(14)C]boceprevir was catalyzed by CYP3A4 and CYP3A5. In addition, the highest turnover was observed in recombinant CYP3A4 and CYP3A5. After a single radiolabeled dose to human, boceprevir was subjected to two distinct pathways, namely cytochrome P450-mediated oxidation and ketone reduction. Therefore, attempts were made to identify the enzymes responsible for the formation of carbonyl-reduced metabolites. Human liver S9 and cytosol converted ∼ 28 and ∼ 68% of boceprevir to M28, respectively, in the presence of an NADPH-generating system. Screening of boceprevir with recombinant human aldo-keto reductases (AKRs) revealed that AKR1C2 and AKR1C3 exhibited catalytic activity with respect to the formation of M+2 metabolites (M28 and M31). The formation of M28 was inhibited by 100 μM flufenamic acid (80.3%), 200 μM mefenamic acid (83.7%), and 100 μM phenolphthalein (86.1%), known inhibitors of AKRs, suggesting its formation through carbonyl reduction pathway. Formation of M28 was also inhibited by 100 μM diazepam (75.1%), 1 mM ibuprofen (70%), and 200 μM diflunisal (89.4%). These data demonstrated that CYP3A4 and CYP3A5 are primarily responsible for the formation of oxidative metabolites and the formation of M28 and M31, the keto-reduced metabolites, are most likely mediated by AKR1C2 and AKR1C3. Because the biotransformation and clearance of boceprevir involves two different enzymatic pathways, boceprevir is less likely to be a victim of significant drug-drug interaction with concomitant medication affecting either of these pathways. PMID:21123164

  12. Novel p53 target genes secreted by the liver are involved in non-cell-autonomous regulation.

    PubMed

    Charni, M; Molchadsky, A; Goldstein, I; Solomon, H; Tal, P; Goldfinger, N; Yang, P; Porat, Z; Lozano, G; Rotter, V

    2016-03-01

    The tumor-suppressor p53 is a transcription factor that prevents cancer development and is involved in regulation of various physiological processes. This is mediated both by induction of cell cycle arrest and apoptosis and by controlling the expression of a plethora of target genes, including secreted proteins. It has been demonstrated that p53 may exert its effect in non-cell-autonomous manner by modulating the expression of genes that encode for secreted factors. In this study, we utilized our microarray data to identify and characterize novel p53 target genes expressed in human liver cells and associated with steroid hormones processing and transfer. We identified the steroid hormones binding factors, sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG) and cytochrome P450 family 21 subfamily A polypeptide 2, as novel p53 target genes. Their expression and secretion was increased following p53 activation in various hepatic cells. We observed that p53 wild-type mice exhibited higher levels of CBG compared with their p53 null counterparts. We demonstrated that the induction of the steroid hormones binding factors can be mediated by binding to specific p53 responsive elements within their promoters. In addition, utilizing conditioned medium experiments we have shown that p53-dependent induction of SHBG secretion from liver cells enhances apoptosis of breast cancer cells. Moreover, depletion of SHBG abolished the induction of breast cancer cells death. The newly identified p53 target genes suggest a novel non-cell-autonomous tumor-suppressive regulation mediated by p53 that is central for maintaining organism homeostasis. PMID:26358154

  13. Liver Biopsy

    MedlinePlus

    ... PDF, 341 KB)​​​​. Alternate Language URL Español Liver Biopsy Page Content On this page: What is a ... to Remember Clinical Trials What is a liver biopsy? A liver biopsy is a procedure that involves ...

  14. Effect of carnitine supplementation on mitochondrial enzymes in liver and skeletal muscle of rat after dietary lipid manipulation and physical activity.

    PubMed

    Karanth, Jyothsna; Jeevaratnam, K

    2010-05-01

    Effect of carnitine supplementation in enhancing fat utilization was investigated by looking into its effects on mitochondrial respiratory enzymes activity in liver and muscle as well as on membrane fatty acid profile in rats fed with hydrogenated fat (HF) and MUFA-rich peanut oil (PO) with or without exercise. Male Wistar rats were fed HF-diet (4 groups, 8 rats in each group) or PO-diet (4 groups, 8 rats in each group), with or without carnitine for 24 weeks. One group for each diet acted as sedentary control while the other groups were allowed swimming for 1 hr a day, 6 days/week, for 24 weeks. The PO diet as well as exercise increased the activities of mitochondrial enzymes, NADH dehydrogenase, NADH oxidase, cytochrome C reductase, cytochrome oxidase, while carnitine supplementation further augmented the oxidative capacity of both liver and muscle significantly by enhancing the activity of carnitine palmitoyl transferase and the respiratory chain enzymes. These effects can be attributed to the enhanced unsaturated fatty acids in phospholipids of mitochondria and may be due to increased fluidity of the membrane in these rats. Results of this study show a significant health promoting effects of carnitine supplementation which could be further augmented by regular exercise. PMID:20795369

  15. Determination of the Mercury Fraction Linked to Protein of Muscle and Liver Tissue of Tucunaré (Cichla spp.) from the Amazon Region of Brazil.

    PubMed

    Vieira, José C S; Cavecci, Bruna; Queiroz, João V; Braga, Camila P; Padilha, Cilene C F; Leite, Aline L; Figueiredo, Wllyane S; Buzalaf, Marília A R; Zara, Luiz F; Padilha, Pedro M

    2015-11-01

    This study used metalloproteomic techniques to characterize mercury (Hg)-bound proteins in the muscle and liver tissue of Tucunaré (Cichla spp.) collected at the Jirau Hydroelectric Power Plant in Madeira River Basin, Brazil. The proteome of the muscle and liver tissue was obtained after two steps of fractional precipitation and separating the proteins by 2-D polyacrylamide gel electrophoresis. Hg was identified and quantified in the protein spots by graphite furnace atomic absorption spectrometry after acid mineralization in an ultrasound bath. Hg with a molecular weight <20 kDa and a concentration between 13.30 and 33.40 mg g(-1) was found in the protein spots. These protein spots were characterized by electrospray ionization tandem mass spectrometry after trypsin digestion. From a total of 12 analyzed spots, seven proteins showing Hg biomarker characteristics were identified: parvalbumin and its isoforms, ubiquitin-40S ribosomal protein S27a, zinc (Zn) finger and BTB domain-containing protein 24, and dual-specificity protein phosphatase 22-B. PMID:25981407

  16. Myosin Heavy Chain Gene Expression in Developing Neonatal Skeletal Muscle: Involvement of the Nerve, Gravity, and Thyroid State

    NASA Technical Reports Server (NTRS)

    Baldwin, K. M.; Adams, G.; Haddad, F.; Zeng, M.; Qin, A.; Qin, L.; McCue, S.; Bodell, P.

    1999-01-01

    The myosin heavy chain (MHC) gene family encodes at least six MHC proteins (herein designated as neonatal, embryonic, slow type I (beta), and fast IIa, IIx, and IIb) that are expressed in skeletal muscle in a muscle-specific and developmentally-regulated fashion. At birth, both antigravity (e.g. soleus) and locomotor (e.g., plantaris) skeletal muscles are undifferentiated relative to the adult MHC phenotype such that the neonatal and embryonic MHC isoforms account for 80 - 90% of the MHC pool in a fast locomotor muscle; whereas, the embryonic and slow, type I isoforms account for approx. 90% of the pool in a typical antigravity muscle. The goal of this study was to investigate the role of an intact nerve, gravity and thyroid hormone (T3), as well as certain interactions of these interventions, on MHC gene expression in developing neonatal skeletal muscles of rodents.

  17. Metal Ion Imbalance-Related Oxidative Stress Is Involved in the Mechanisms of Liver Injury in a Rat Model of Chronic Aluminum Exposure.

    PubMed

    Yang, Yang; Wang, Hong; Guo, Yuanxin; Lei, Wenjuan; Wang, Jianfeng; Hu, Xinyue; Yang, Junqing; He, Qin

    2016-09-01

    The objective of the study is to investigate the effects of chronic aluminum overload on rat liver function and its induction of pathological changes in metal ion levels and oxidative stress in hepatic tissues. Wistar rats were intragastrically administered aluminum gluconate (200 mg Al(3+)/Kg) once a day, 5 days a week, for 20 weeks. HE staining was used to visualize pathological changes in rat liver tissue. A biochemical method was adopted to detect ALT, AST, ALP, and GGT levels, as well as liver SOD activity and blood plasma MDA content. A plasma atomic emission spectrophotometer was used to detect Al, Mn, Fe, Zn, and Cu ion contents in liver tissue. Our results showed obvious vacuolar degeneration, granular degeneration, and spotty necrosis in chronic Al-overload rat hepatocytes. The levels of ALT, AST, ALP, and GGT were significantly increased. Liver SOD activity was significantly decreased, and MDA content was significantly increased. In Al-overload rat liver, Al, Mn, Fe, and Cu contents were significantly increased, and in Al-overload rat serum, Mn, Fe, Zn, and Cu contents were significantly decreased. However, the Al level in Al-overload rat serum was not significantly different from that in control rat serum. These results suggest that chronic aluminum overload causes obvious damage to rat liver and causes imbalances in Al, Mn, Fe, Zn, and Cu levels in rat liver and serum. Metal ion imbalance-related oxidative stress may be involved in the mechanism of chronic liver injury caused by aluminum overload. PMID:26811106

  18. The Selenium Deficiency Disease Exudative Diathesis in Chicks Is Associated with Downregulation of Seven Common Selenoprotein Genes in Liver and Muscle123

    PubMed Central

    Huang, Jia-Qiang; Li, Dai-Lin; Zhao, Hua; Sun, Lv-Hui; Xia, Xin-Jie; Wang, Kang-Ning; Luo, Xugang; Lei, Xin Gen

    2011-01-01

    Fast-growing broiler chicks are susceptible to Se deficiency diseases including exudative diathesis (ED). Our objective was to determine if ED could be induced by feeding a current, practical diet and if the incidence was related to selenogenome expression in liver and muscle of chicks. Four groups of day-old broiler chicks (n = 60/group) were fed a corn-soy basal diet (BD; 14 μg Se/kg; produced in the Se-deficient area of Sichuan, China and not supplemented with Se or vitamin E), the BD and all-rac-α-tocopheryl acetate at 50 mg/kg and Se (as sodium selenite) at 0.3 mg/kg, or both of these nutrients for 6 wk. A high incidence of ED and mortality of chicks were induced by the BD. The incidences and mortality were completely prevented by supplemental dietary Se but were only partially decreased by supplemental α-tocopherol acetate. Dietary Se deficiency decreased (P < 0.05) mRNA levels of 7 common selenoprotein genes (Gpx1, Gpx4, Sepw1, Sepn1, Sepp1, Selo, and Selk) in muscle and liver. Whereas supplementing α-tocopherol acetate enhanced (P < 0.05) only the muscle Sepx1 mRNA level, it actually decreased (P < 0.05) hepatic Gpx1, Seli, Txnrd1, and Txnrd2 mRNA levels. In conclusion, dietary Se protected chicks from the Se deficiency disease ED, probably by upregulating selenoprotein genes coding for oxidation- and/or lesion-protective proteins. The protection by vitamin E might be mediated via selenoproteins not assayed in this study and/or Se-independent mechanisms. The inverse relationship between hepatic expression of 4 redox-related selenoprotein genes and vitamin E status revealed a novel interaction between Se and vitamin E in vivo. PMID:21795426

  19. The Effects of Group Relaxation Training/Large Muscle Exercise, and Parental Involvement on Attention to Task, Impulsivity, and Locus of Control among Hyperactive Boys.

    ERIC Educational Resources Information Center

    Porter, Sally S.; Omizo, Michael M.

    1984-01-01

    The study examined the effects of group relaxation training/large muscle exercise and parental involvement on attention to task, impulsivity, and locus of control among 34 hyperactive boys. Following treatment both experimental groups recorded significantly higher attention to task, lower impulsivity, and lower locus of control scores. (Author/CL)

  20. Involvement of the Antioxidant Effect and Anti-inflammatory Response in Butyrate-Inhibited Vascular Smooth Muscle Cell Proliferation

    PubMed Central

    Mathew, Omana P.; Ranganna, Kasturi; Milton, Shirlette G.

    2014-01-01

    Epigenetic mechanisms by altering the expression and, in turn, functions of target genes have potential to modify cellular processes that are characteristics of atherosclerosis, including inflammation, proliferation, migration and apoptosis/cell death. Butyrate, a natural epigenetic modifier and a histone deacetylase inhibitor (HDACi), is an inhibitor of vascular smooth muscle cell (VSMC) proliferation, a critical event in atherogenesis. Here, we examined whether glutathione peroxidases (GPxs), a family of antioxidant enzymes, are modulated by butyrate, contributing to its antiproliferation action on VSMC through the regulation of the inflammatory response by using western blotting, immunostaining methods and activity assay. Treatment of VSMC with butyrate not only upregulates glutathione peroxidase (GPx) 3 and GPx4, but also increases the overall catalytic activity of GPx supporting involvement of antioxidant effect in butyrate arrested VSMC proliferation. Moreover, analysis of the redox-sensitive NF-κB transcription factor system, the target of GPx, reveals that butyrate causes downregulation of IKKα, IKKβ, IkBα and NF-κBp65 expression and prevents NF-κBp65 phosphorylation at serine536 causing inhibition of the expression NF-κB target inflammatory genes, including inducible nitric oxide synthase, VCAM-1 and cyclooxygenase-2. Overall, these observations suggest a link between the antioxidant effect and anti-inflammatory response in butyrate-arrested VSMC proliferation, accentuating the atheroprotective and therapeutic potential of natural products, like butyrate, in vascular proliferative diseases. PMID:25390157

  1. The TWEAK-Fn14 dyad is involved in age-associated pathological changes in skeletal muscle

    PubMed Central

    Shin, Jonghyun; Zheng, Timothy S.; Burkly, Linda C.; Kumar, Ashok

    2014-01-01

    Progressive loss of skeletal muscle mass and strength (sarcopenia) is a major clinical problem in the elderly. Recently, proinflammatory cytokine TWEAK and its receptor Fn14 were identified as key mediators of muscle wasting in various catabolic states. However, the role of the TWEAK-Fn14 pathway in pathological changes in skeletal muscle during aging remains unknown. In this study, we demonstrate that the levels of Fn14 are increased in skeletal muscle of 18-month old (aged) mice compared with adult mice. Genetic ablation of Fn14 significantly increased the levels of specific muscle proteins and blunted the age-associated fiber atrophy in mice. While gene expression of two prominent muscle-specific E3 ubiquitin ligases MAFBx and MuRF1 remained comparable, levels of ubiquitinated proteins and the expression of autophagy-related molecule Atg12 was significantly reduced in Fn14-knockout (KO) mice compared with wild-type mice during aging. Ablation of Fn14 significantly diminished the DNA-binding activity of transcription factor nuclear factor-kappa B (NF-κB), gene expression of various inflammatory molecules, and interstitial fibrosis in skeletal muscle of aged mice. Collectively, our study suggests that the TWEAK-Fn14 signaling axis contributes to age-associated muscle atrophy and fibrosis potentially through its local activation of proteolytic systems and inflammatory pathways. PMID:24680686

  2. [Skeletal muscle involvement in enthesopathy of the lateral epicondyle of the humerus (so-called tennis elbow)].

    PubMed

    Janda, J; Koudela, K

    1988-01-01

    Muscle specimens from the origin of the m. extensor carpi radialis brevis, were obtained from 53 patients suffering from chronic enthesopathy of the lateral epicondyle of humerus (EELH). Frank neurogenic atrophy as well as disuse atrophy were caused by radicular irritation due to the cervicobrachial syndrome. The borderline and/or reinnervation patterns of the muscle lesion may be due to the compression neuropathy of the peripheral branches of the radial nerve or may reflect adaptation of the muscle to the chronic nociceptive stimulation in sense of chronic reflex atrophy of the muscle. The elbow joint, and especially the humeroradial joint in cases of EELH represents a functional unit. Any damage to any part leads to secondary reparative and adaptive changes in other structures including the muscle. PMID:2970182

  3. β2-Adrenoceptor is involved in connective tissue remodeling in regenerating muscles by decreasing the activity of MMP-9.

    PubMed

    Silva, Meiricris T; Nascimento, Tábata L; Pereira, Marcelo G; Siqueira, Adriane S; Brum, Patrícia C; Jaeger, Ruy G; Miyabara, Elen H

    2016-07-01

    We investigated the role of β2-adrenoceptors in the connective tissue remodeling of regenerating muscles from β2-adrenoceptor knockout (β2KO) mice. Tibialis anterior muscles from β2KO mice were cryolesioned and analyzed after 3, 10, and 21 days. Regenerating muscles from β2KO mice showed a significant increase in the area density of the connective tissue and in the amount of collagen at 10 days compared with wild-type (WT) mice. A greater increase occurred in the expression levels of collagen I, III, and IV in regenerating muscles from β2KO mice evaluated at 10 days compared with WT mice; this increase continued at 21 days, except for collagen III. Matrix metalloproteinase (MMP-2) activity increased to a similar extent in regenerating muscles from both β2KO and WT mice at 3 and 10 days. This was also the case for MMP-9 activity in regenerating muscles from both β2KO and WT mice at 3 days; however, at 10 days post-cryolesion, this activity returned to baseline levels only in WT mice. MMP-3 activity was unaltered in regenerating muscles at 10 days. mRNA levels of tumor necrosis factor-α increased in regenerating muscles from WT and β2KO mice at 3 days and, at 10 days post-cryolesion, returned to baseline only in WT mice. mRNA levels of interleukin-6 increased in muscles from WT mice at 3 days post-cryolesion and returned to baseline at 10 days post-cryolesion but were unchanged in β2KO mice. Our results suggest that the β2-adrenoceptor contributes to collagen remodeling during muscle regeneration by decreasing MMP-9 activity. PMID:26896238

  4. Cannabinoid receptors are involved in the protective effect of a novel curcumin derivative C66 against CCl4-induced liver fibrosis.

    PubMed

    Huang, Si-Si; Chen, Da-Zhi; Wu, He; Chen, Rui-Cong; Du, Shan-Jie; Dong, Jia-Jia; Liang, Guang; Xu, Lan-Man; Wang, Xiao-Dong; Yang, Yong-Ping; Yu, Zhen-Ping; Feng, Wen-Ke; Chen, Yong-Ping

    2016-05-15

    Liver fibrosis is one of the major causes of morbidity and mortality worldwide and lacks efficient therapy. Recent studies suggest the curcumin protects liver from fibrosis. However, curcumin itself is in low bioavailable concentration when administered orally, and the protective mechanism remains poorly understood. The current study aimed to investigate whether a more stable derivative of curcumin, C66, protects against CCl4-inudced liver fibrosis and examine the underlying mechanism involving cannabinoid receptor (CB receptor). At a dose lower than curcumin itself, C66 displayed a superior anti-fibrotic effect. C66 significantly reduced collagen deposition, pro-inflammatory cytokine expression, and liver enzyme activities. Mechanistic study revealed that C66 treatment decreased CCl4-induced cannabinoid receptor 1 (CB1 receptor) expression and increased cannabinoid receptor 2 (CB2 receptor) expression, along with an inhibition of JNK/NF-κB-mediated inflammatory signaling. In conclusion, this curcumin derivative attenuates liver fibrosis likely involving a CB/JNK/NF-κB-mediated pathway. PMID:26945822

  5. Effects of peroxisome proliferators on rat liver phospholipids: sphingomyelin degradation may be involved in hepatotoxic mechanism of perfluorodecanoic acid.

    PubMed

    Adinehzadeh, M; Reo, N V

    1998-05-01

    Perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), clofibrate, di(2-ethylhexyl)phthalate (DEHP), and Wy-14,643 represent a class of compounds known as peroxisome proliferators (PPs). Such compounds induce biogenesis of liver peroxisomes and cause a varying degree of hepatotoxicity and carcinogenesis in rodents. We examined the effects of these PPs on rat hepatic lipids and phospholipid profiles using phosphorus-31 NMR spectroscopy. All PPs caused a 25-57% increase in hepatic phospholipid content, while all but clofibrate increased the total lipid content by 26-156%. Treatments also influenced the composition of liver phospholipids. Phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEth) contents were significantly increased in all treatment groups. Most notably, PFDA caused the largest increase in PtdCho and PtdEth content (ca. 70%), while PFOA and Wy-14,643 were the only test compounds that influenced the PtdCho:PtdEth ratio. PFDA also caused an ca. 30% decrease in sphingomyelin (SphM) from 24 to 120 h postdose. SphM is a key lipid in signal transduction processes involved in apoptosis. Hydrolysis of SphM can be mediated through the action of tumor necrosis factor (TNF-alpha). We measured the TNF-alpha concentrations in rat sera at 24 h post-PFDA-exposure and found an 8-fold increase relative to vehicle-treated controls. These data demonstrate that an increase in the serum TNF-alpha level correlates with the time frame for the observed reduction in hepatic SphM. PFOA, a structurally similar compound, had no effect on hepatic SphM content, nor did it affect the serum TNF-alpha concentration. These effects may be related to differences in the tumorigenicity associated with these compounds. We postulate that PFDA activates the SphM signal transduction pathway via the release of TNF-alpha. This then stimulates cytotoxic responses and processes of apoptosis and may suppress cell proliferative and mitogenic responses. PMID:9585473

  6. Prostaglandin and myokine involvement in the cyclooxygenase-inhibiting drug enhancement of skeletal muscle adaptations to resistance exercise in older adults.

    PubMed

    Trappe, Todd A; Standley, Robert A; Jemiolo, Bozena; Carroll, Chad C; Trappe, Scott W

    2013-02-01

    Twelve weeks of resistance training (3 days/wk) combined with daily consumption of the cyclooxygenase-inhibiting drugs acetaminophen (4.0 g/day; n = 11, 64 ± 1 yr) or ibuprofen (1.2 g/day; n = 13, 64 ± 1 yr) unexpectedly promoted muscle mass and strength gains 25-50% above placebo (n = 12, 67 ± 2 yr). To investigate the mechanism of this adaptation, muscle biopsies obtained before and ∼72 h after the last training bout were analyzed for mRNA levels of prostaglandin (PG)/cyclooxygenase pathway enzymes and receptors [arachidonic acid synthesis: cytosolic phospholipase A(2) (cPLA(2)) and secreted phospholipase A(2) (sPLA(2)); PGF(2α) synthesis: PGF(2α) synthase and PGE(2) to PGF(2α) reductase; PGE(2) synthesis: PGE(2) synthase-1, -2, and -3; PGF(2α) receptor and PGE(2) receptor-4], cytokines and myokines involved in skeletal muscle adaptation (TNF-α, IL-1β, IL-6, IL-8, IL-10), and regulators of muscle growth [myogenin, myogenic regulatory factor-4 (MRF4), myostatin] and atrophy [Forkhead box O3A (FOXO3A), atrogin-1, muscle RING finger protein 1 (MuRF-1), inhibitory κB kinase β (IKKβ)]. Training increased (P < 0.05) cPLA(2), PGF(2α) synthase, PGE(2) to PGF(2α) reductase, PGE(2) receptor-4, TNF-α, IL-1β, IL-8, and IKKβ. However, the PGF(2α) receptor was upregulated (P < 0.05) only in the drug groups, and the placebo group upregulation (P < 0.05) of IL-6, IL-10, and MuRF-1 was eliminated in both drug groups. These results highlight prostaglandin and myokine involvement in the adaptive response to exercise in older individuals and suggest two mechanisms underlying the enhanced muscle mass gains in the drug groups: 1) The drug-induced PGF(2α) receptor upregulation helped offset the drug suppression of PGF(2α)-stimulated protein synthesis after each exercise bout and enhanced skeletal muscle sensitivity to this stimulation. 2) The drug-induced suppression of intramuscular PGE(2) production increased net muscle protein balance after each exercise bout

  7. Distinct α2 Na,K-ATPase membrane pools are differently involved in early skeletal muscle remodeling during disuse

    PubMed Central

    Kravtsova, Violetta V.; Petrov, Alexey M.; Matchkov, Vladimir V.; Bouzinova, Elena V.; Vasiliev, Alexander N.; Benziane, Boubacar; Zefirov, Andrey L.; Chibalin, Alexander V.; Heiny, Judith A.

    2016-01-01

    The Na,K-ATPase is essential for the contractile function of skeletal muscle, which expresses the α1 and α2 subunit isoforms of Na,K-ATPase. The α2 isozyme is predominant in adult skeletal muscles and makes a greater contribution in working compared with noncontracting muscles. Hindlimb suspension (HS) is a widely used model of muscle disuse that leads to progressive atrophy of postural skeletal muscles. This study examines the consequences of acute (6–12 h) HS on the functioning of the Na,K-ATPase α1 and α2 isozymes in rat soleus (disused) and diaphragm (contracting) muscles. Acute disuse dynamically and isoform-specifically regulates the electrogenic activity, protein, and mRNA content of Na,K-ATPase α2 isozyme in rat soleus muscle. Earlier disuse-induced remodeling events also include phospholemman phosphorylation as well as its increased abundance and association with α2 Na,K-ATPase. The loss of α2 Na,K-ATPase activity results in reduced electrogenic pump transport and depolarized resting membrane potential. The decreased α2 Na,K-ATPase activity is caused by a decrease in enzyme activity rather than by altered protein and mRNA content, localization in the sarcolemma, or functional interaction with the nicotinic acetylcholine receptors. The loss of extrajunctional α2 Na,K-ATPase activity depends strongly on muscle use, and even the increased protein and mRNA content as well as enhanced α2 Na,K-ATPase abundance at this membrane region after 12 h of HS cannot counteract this sustained inhibition. In contrast, additional factors may regulate the subset of junctional α2 Na,K-ATPase pool that is able to recover during HS. Notably, acute, low-intensity muscle workload restores functioning of both α2 Na,K-ATPase pools. These results demonstrate that the α2 Na,K-ATPase in rat skeletal muscle is dynamically and acutely regulated by muscle use and provide the first evidence that the junctional and extrajunctional pools of the α2 Na,K-ATPase are regulated

  8. Levels of metals in kidney, liver and muscle tissue and their relation to the occurrence of parasites in the red fox in the Lower Silesian Forest in Europe.

    PubMed

    Binkowski, Łukasz J; Merta, Dorota; Przystupińska, Anna; Sołtysiak, Zenon; Pacoń, Jarosław; Stawarz, Robert

    2016-04-01

    Together with the occurrence of parasites, increased concentrations of xenobiotics, to which scavengers are greatly exposed, may significantly influence the physiology of red foxes. It is also suspected that these two factors interact. The accumulation of various metals (Ca, Cd, Cu, Fe, Hg, K, Mg, Ni, Pb, Zn) in kidney, liver and muscle tissue was investigated, as well as the occurrence of parasites, and the potential link to the presence of metals. Generally speaking, neither sex nor age influenced these concentrations. K, Mg and Fe were found in the highest concentrations and Hg was found in the lowest. Various relationships between the concentrations of metals were observed in the tissues. 34% of the specimens studied were hosts to parasites. No clear, significant connection between the concentrations and the occurrence of parasites was noted, but the discernible trend confirmed by the logistic regression, needs further study. PMID:26855220

  9. AAV2/8 Vectors Purified from Culture Medium with a Simple and Rapid Protocol Transduce Murine Liver, Muscle, and Retina Efficiently

    PubMed Central

    Doria, Monica; Ferrara, Antonella

    2013-01-01

    Abstract During the production of some adeno-associated virus (AAV) serotypes, a large amount of vectors is found in the medium of producing cells. For their purification, previous protocols used tangential flow filtration (TFF) of the medium followed by iodixanol gradient centrifugation. Taking advantage of the higher purity of the medium than the cell-derived material as the source of AAV, we tested a simple method that combines production of large culture medium volumes containing AAV from cell stacks with medium clarification+TFF without further time-consuming and nonscalable centrifugation. To test this, we selected AAV2/8, which is emerging as a favored serotype for transduction of liver, muscle, and retina and abundantly found in the extracellular medium. We show that yields and in vitro infectivity of AAV2/8 vectors produced from the culture medium using this method are higher than those of vectors purified from the same cell lysate using a conventional CsCl2 gradient ultracentrifugation-based method, although purity appears inferior. In addition, we found that the transduction efficiency of AAV2/8 purified from medium was similar to that of AAV2/8 purified from the same cell lysate in the murine liver, muscle, and retina. Considering that the purification protocol from the medium we describe requires 3 hr as opposed to the 63 hr of a conventional two-round CsCl2-gradient ultracentrifugation+desalting, we conclude that TFF of the medium containing AAV2/8 represents a quick and scalable method to purify research-grade vectors for use in animal models. PMID:24116943

  10. Skeletal muscle as an endogenous nitrate reservoir

    PubMed Central

    Piknova, Barbora; Park, Ji Won; Swanson, Kathryn M.; Dey, Soumyadeep; Noguchi, Constance Tom; Schechter, Alan N

    2015-01-01

    The nitric oxide synthase (NOS) family of enzymes form nitric oxide (NO) from arginine in the presence of oxygen. At reduced oxygen availability NO is also generated from nitrate in a two step process by bacterial and mammalian molybdopterin proteins, and also directly from nitrite by a variety of five-coordinated ferrous hemoproteins. The mammalian NO cycle also involves direct oxidation of NO to nitrite, and both NO and nitrite to nitrate by oxy-ferrous hemoproteins. The liver and blood are considered the sites of active mammalian NO metabolism and nitrite and nitrate concentrations in the liver and blood of several mammalian species, including human, have been determined. However, the large tissue mass of skeletal muscle had not been generally considered in the analysis of the NO cycle, in spite of its long-known presence of significant levels of active neuronal NOS (nNOS or NOS1). We hypothesized that skeletal muscle participates in the NO cycle and, due to its NO oxidizing heme protein, oxymyoglobin, has high concentrations of nitrate ions. We measured nitrite and nitrate concentrations in rat and mouse leg skeletal muscle and found unusually high concentrations of nitrate but similar levels of nitrite, when compared to the liver. The nitrate reservoir in muscle is easily accessible via the bloodstream and therefore nitrate is available for transport to internal organs where it can be reduced to nitrite and NO. Nitrate levels in skeletal muscle and blood in nNOS−/− mice were dramatically lower when compared with controls, which support further our hypothesis. Although the nitrate reductase activity of xanthine oxidoreductase in muscle is less than that of liver, the residual activity in muscle could be very important in view of its total mass and the high basal level of nitrate. We suggest that skeletal muscle participates in overall NO metabolism, serving as a nitrate reservoir, for direct formation of nitrite and NO, and for determining levels of nitrate