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Sample records for lactation promotes nonalcoholic

  1. A maternal "junk food" diet in pregnancy and lactation promotes nonalcoholic Fatty liver disease in rat offspring.

    PubMed

    Bayol, Stéphanie A; Simbi, Bigboy H; Fowkes, Robert C; Stickland, Neil C

    2010-04-01

    With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring.

  2. A Maternal “Junk Food” Diet in Pregnancy and Lactation Promotes Nonalcoholic Fatty Liver Disease in Rat Offspring

    PubMed Central

    Bayol, Stéphanie A.; Simbi, Bigboy H.; Fowkes, Robert C.; Stickland, Neil C.

    2010-01-01

    With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring. PMID:20207831

  3. Monitoring food and non-alcoholic beverage promotions to children.

    PubMed

    Kelly, B; King, L; Baur, L; Rayner, M; Lobstein, T; Monteiro, C; Macmullan, J; Mohan, S; Barquera, S; Friel, S; Hawkes, C; Kumanyika, S; L'Abbé, M; Lee, A; Ma, J; Neal, B; Sacks, G; Sanders, D; Snowdon, W; Swinburn, B; Vandevijvere, S; Walker, C

    2013-10-01

    Food and non-alcoholic beverage marketing is recognized as an important factor influencing food choices related to non-communicable diseases. The monitoring of populations' exposure to food and non-alcoholic beverage promotions, and the content of these promotions, is necessary to generate evidence to understand the extent of the problem, and to determine appropriate and effective policy responses. A review of studies measuring the nature and extent of exposure to food promotions was conducted to identify approaches to monitoring food promotions via dominant media platforms. A step-wise approach, comprising 'minimal', 'expanded' and 'optimal' monitoring activities, was designed. This approach can be used to assess the frequency and level of exposure of population groups (especially children) to food promotions, the persuasive power of techniques used in promotional communications (power of promotions) and the nutritional composition of promoted food products. Detailed procedures for data sampling, data collection and data analysis for a range of media types are presented, as well as quantifiable measurement indicators for assessing exposure to and power of food and non-alcoholic beverage promotions. The proposed framework supports the development of a consistent system for monitoring food and non-alcoholic beverage promotions for comparison between countries and over time.

  4. Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease

    PubMed Central

    Gentric, Géraldine; Maillet, Vanessa; Paradis, Valérie; Couton, Dominique; L’Hermitte, Antoine; Panasyuk, Ganna; Fromenty, Bernard; Celton-Morizur, Séverine; Desdouets, Chantal

    2015-01-01

    Polyploidization is one of the most dramatic changes that can occur in the genome. In the liver, physiological polyploidization events occur during both liver development and throughout adult life. Here, we determined that a pathological polyploidization takes place in nonalcoholic fatty liver disease (NAFLD), a widespread hepatic metabolic disorder that is believed to be a risk factor for hepatocellular carcinoma (HCC). In murine models of NAFLD, the parenchyma of fatty livers displayed alterations of the polyploidization process, including the presence of a large proportion of highly polyploid mononuclear cells, which are rarely observed in normal hepatic parenchyma. Biopsies from patients with nonalcoholic steatohepatitis (NASH) revealed the presence of alterations in hepatocyte ploidy compared with tissue from control individuals. Hepatocytes from NAFLD mice revealed that progression through the S/G2 phases of the cell cycle was inefficient. This alteration was associated with activation of a G2/M DNA damage checkpoint, which prevented activation of the cyclin B1/CDK1 complex. Furthermore, we determined that oxidative stress promotes the appearance of highly polyploid cells, and antioxidant-treated NAFLD hepatocytes resumed normal cell division and returned to a physiological state of polyploidy. Collectively, these findings indicate that oxidative stress promotes pathological polyploidization and suggest that this is an early event in NAFLD that may contribute to HCC development. PMID:25621497

  5. Lactate promotes glutamine uptake and metabolism in oxidative cancer cells.

    PubMed

    Pérez-Escuredo, Jhudit; Dadhich, Rajesh K; Dhup, Suveera; Cacace, Andrea; Van Hée, Vincent F; De Saedeleer, Christophe J; Sboarina, Martina; Rodriguez, Fabien; Fontenille, Marie-Joséphine; Brisson, Lucie; Porporato, Paolo E; Sonveaux, Pierre

    2016-01-01

    Oxygenated cancer cells have a high metabolic plasticity as they can use glucose, glutamine and lactate as main substrates to support their bioenergetic and biosynthetic activities. Metabolic optimization requires integration. While glycolysis and glutaminolysis can cooperate to support cellular proliferation, oxidative lactate metabolism opposes glycolysis in oxidative cancer cells engaged in a symbiotic relation with their hypoxic/glycolytic neighbors. However, little is known concerning the relationship between oxidative lactate metabolism and glutamine metabolism. Using SiHa and HeLa human cancer cells, this study reports that intracellular lactate signaling promotes glutamine uptake and metabolism in oxidative cancer cells. It depends on the uptake of extracellular lactate by monocarboxylate transporter 1 (MCT1). Lactate first stabilizes hypoxia-inducible factor-2α (HIF-2α), and HIF-2α then transactivates c-Myc in a pathway that mimics a response to hypoxia. Consequently, lactate-induced c-Myc activation triggers the expression of glutamine transporter ASCT2 and of glutaminase 1 (GLS1), resulting in improved glutamine uptake and catabolism. Elucidation of this metabolic dependence could be of therapeutic interest. First, inhibitors of lactate uptake targeting MCT1 are currently entering clinical trials. They have the potential to indirectly repress glutaminolysis. Second, in oxidative cancer cells, resistance to glutaminolysis inhibition could arise from compensation by oxidative lactate metabolism and increased lactate signaling.

  6. Lactate promotes glutamine uptake and metabolism in oxidative cancer cells

    PubMed Central

    Pérez-Escuredo, Jhudit; Dadhich, Rajesh K; Dhup, Suveera; Cacace, Andrea; Van Hée, Vincent F; De Saedeleer, Christophe J; Sboarina, Martina; Rodriguez, Fabien; Fontenille, Marie-Joséphine; Brisson, Lucie; Porporato, Paolo E; Sonveaux, Pierre

    2016-01-01

    ABSTRACT Oxygenated cancer cells have a high metabolic plasticity as they can use glucose, glutamine and lactate as main substrates to support their bioenergetic and biosynthetic activities. Metabolic optimization requires integration. While glycolysis and glutaminolysis can cooperate to support cellular proliferation, oxidative lactate metabolism opposes glycolysis in oxidative cancer cells engaged in a symbiotic relation with their hypoxic/glycolytic neighbors. However, little is known concerning the relationship between oxidative lactate metabolism and glutamine metabolism. Using SiHa and HeLa human cancer cells, this study reports that intracellular lactate signaling promotes glutamine uptake and metabolism in oxidative cancer cells. It depends on the uptake of extracellular lactate by monocarboxylate transporter 1 (MCT1). Lactate first stabilizes hypoxia-inducible factor-2α (HIF-2α), and HIF-2α then transactivates c-Myc in a pathway that mimics a response to hypoxia. Consequently, lactate-induced c-Myc activation triggers the expression of glutamine transporter ASCT2 and of glutaminase 1 (GLS1), resulting in improved glutamine uptake and catabolism. Elucidation of this metabolic dependence could be of therapeutic interest. First, inhibitors of lactate uptake targeting MCT1 are currently entering clinical trials. They have the potential to indirectly repress glutaminolysis. Second, in oxidative cancer cells, resistance to glutaminolysis inhibition could arise from compensation by oxidative lactate metabolism and increased lactate signaling. PMID:26636483

  7. Nonalcoholic Steatohepatitis Induced by a High-Fat Diet Promotes Diethylnitrosamine Initiated Early Hepatocarcinogenesis in Rats

    USDA-ARS?s Scientific Manuscript database

    It has been suggested that patients with nonalcoholic steatohepatitis (NASH) have a high risk for liver cancer. However, it is unknown whether high-fat diet induced NASH promotes chemical carcinogen-initiated hepatocarcinogenesis. In the present study, Sprague-Dawley rats were injected with a low d...

  8. Nonalcoholic steatohepatitis induced by a high-fat diet promotes diethylnitrosamine initiated early hepatocarcinogenesis in rats

    USDA-ARS?s Scientific Manuscript database

    It has been suggested that patients with nonalcoholic steatohepatitis (NASH) are at a high risk for liver cancer. However, it is unknown whether high-fat diet induced NASH promotes hepatocarcinogenesis. In the present study, Sprague-Dawley rats were injected with a low dose of hepatic carcinogen die...

  9. Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease.

    PubMed

    Jiang, Changtao; Xie, Cen; Li, Fei; Zhang, Limin; Nichols, Robert G; Krausz, Kristopher W; Cai, Jingwei; Qi, Yunpeng; Fang, Zhong-Ze; Takahashi, Shogo; Tanaka, Naoki; Desai, Dhimant; Amin, Shantu G; Albert, Istvan; Patterson, Andrew D; Gonzalez, Frank J

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a major worldwide health problem. Recent studies suggest that the gut microbiota influences NAFLD pathogenesis. Here, a murine model of high-fat diet-induced (HFD-induced) NAFLD was used, and the effects of alterations in the gut microbiota on NAFLD were determined. Mice treated with antibiotics or tempol exhibited altered bile acid composition, with a notable increase in conjugated bile acid metabolites that inhibited intestinal farnesoid X receptor (FXR) signaling. Compared with control mice, animals with intestine-specific Fxr disruption had reduced hepatic triglyceride accumulation in response to a HFD. The decrease in hepatic triglyceride accumulation was mainly due to fewer circulating ceramides, which was in part the result of lower expression of ceramide synthesis genes. The reduction of ceramide levels in the ileum and serum in tempol- or antibiotic-treated mice fed a HFD resulted in downregulation of hepatic SREBP1C and decreased de novo lipogenesis. Administration of C16:0 ceramide to antibiotic-treated mice fed a HFD reversed hepatic steatosis. These studies demonstrate that inhibition of an intestinal FXR/ceramide axis mediates gut microbiota-associated NAFLD development, linking the microbiome, nuclear receptor signaling, and NAFLD. This work suggests that inhibition of intestinal FXR is a potential therapeutic target for NAFLD treatment.

  10. Impaired SUMOylation of nuclear receptor LRH-1 promotes nonalcoholic fatty liver disease.

    PubMed

    Stein, Sokrates; Lemos, Vera; Xu, Pan; Demagny, Hadrien; Wang, Xu; Ryu, Dongryeol; Jimenez, Veronica; Bosch, Fatima; Lüscher, Thomas F; Oosterveer, Maaike H; Schoonjans, Kristina

    2017-02-01

    Hepatic steatosis is caused by metabolic imbalances that could be explained in part by an increase in de novo lipogenesis that results from increased sterol element binding protein 1 (SREBP-1) activity. The nuclear receptor liver receptor homolog 1 (LRH-1) is an important regulator of intermediary metabolism in the liver, but its role in regulating lipogenesis is not well understood. Here, we have assessed the contribution of LRH-1 SUMOylation to the development of nonalcoholic fatty liver disease (NAFLD). Mice expressing a SUMOylation-defective mutant of LRH-1 (LRH-1 K289R mice) developed NAFLD and early signs of nonalcoholic steatohepatitis (NASH) when challenged with a lipogenic, high-fat, high-sucrose diet. Moreover, we observed that the LRH-1 K289R mutation induced the expression of oxysterol binding protein-like 3 (OSBPL3), enhanced SREBP-1 processing, and promoted de novo lipogenesis. Mechanistically, we demonstrated that ectopic expression of OSBPL3 facilitates SREBP-1 processing in WT mice, while silencing hepatic Osbpl3 reverses the lipogenic phenotype of LRH-1 K289R mice. These findings suggest that compromised SUMOylation of LRH-1 promotes the development of NAFLD under lipogenic conditions through regulation of OSBPL3.

  11. Impaired SUMOylation of nuclear receptor LRH-1 promotes nonalcoholic fatty liver disease

    PubMed Central

    Lemos, Vera; Xu, Pan; Jimenez, Veronica; Bosch, Fatima; Lüscher, Thomas F.; Oosterveer, Maaike H.

    2017-01-01

    Hepatic steatosis is caused by metabolic imbalances that could be explained in part by an increase in de novo lipogenesis that results from increased sterol element binding protein 1 (SREBP-1) activity. The nuclear receptor liver receptor homolog 1 (LRH-1) is an important regulator of intermediary metabolism in the liver, but its role in regulating lipogenesis is not well understood. Here, we have assessed the contribution of LRH-1 SUMOylation to the development of nonalcoholic fatty liver disease (NAFLD). Mice expressing a SUMOylation-defective mutant of LRH-1 (LRH-1 K289R mice) developed NAFLD and early signs of nonalcoholic steatohepatitis (NASH) when challenged with a lipogenic, high-fat, high-sucrose diet. Moreover, we observed that the LRH-1 K289R mutation induced the expression of oxysterol binding protein-like 3 (OSBPL3), enhanced SREBP-1 processing, and promoted de novo lipogenesis. Mechanistically, we demonstrated that ectopic expression of OSBPL3 facilitates SREBP-1 processing in WT mice, while silencing hepatic Osbpl3 reverses the lipogenic phenotype of LRH-1 K289R mice. These findings suggest that compromised SUMOylation of LRH-1 promotes the development of NAFLD under lipogenic conditions through regulation of OSBPL3. PMID:28094767

  12. Lactation

    PubMed Central

    1989-01-01

    Lactation is the most energy-efficient way to provide for the dietary needs of young mammals, their mother's milk being actively protective, immunomodulatory, and ideal for their needs. Intrauterine mammary gland development in the human female is already apparent by the end of the sixth week of gestation. During puberty and adolescence secretions of the anterior pituitary stimulate the maturation of the graafian follicles in the ovaries and stimulate the secretion of follicular estrogens, which stimulate development of the mammary ducts. Pregnancy has the most dramatic effect on the breast, but development of the glandular breast tissue and deposition of fat and connective tissue continue under the influence of cyclic sex-hormone stimulation. Many changes occur in the nipple and breast during pregnancy and at delivery as a prelude to lactation. Preparation of the breasts is so effective that lactation could commence even if pregnancy were discontinued at 16 weeks. Following birth, placental inhibition of milk synthesis is removed, and a woman's progesterone blood levels decline rapidly. The breasts fill with milk, which is a high-density, low-volume feed called colostrum until about 30 hours after birth. Because it is not the level of maternal hormones, but the efficiency of infant suckling and/or milk removal that governs the volume of milk produced in each breast, mothers who permit their infants to feed ad libitum commonly observe that they have large volumes of milk 24-48 hours after birth. The two maternal reflexes involved in lactation are the milk-production and milk-ejection reflex. A number of complementary reflexes are involved when the infant feeds: the rooting reflex (which programmes the infant to search for the nipple), the sucking reflex (rhythmic jaw action creating negative pressure and a peristaltic action of the tongue), and the swallowing reflex. The infant's instinctive actions need to be consolidated into learned behaviour in the postpartum

  13. Lactation Consultant

    MedlinePlus

    ... human lactation. Job description Lactation consultants educate women, families, health professionals, and the community about breast feeding and human lactation; facilitate the development of policies which protect, promote, and support breastfeeding; ...

  14. Oligodendrocyte Progenitor Cells Directly Utilize Lactate for Promoting Cell Cycling and Differentiation.

    PubMed

    Ichihara, Yoshinori; Doi, Toru; Ryu, Youngjae; Nagao, Motoshi; Sawada, Yasuhiro; Ogata, Toru

    2017-05-01

    Oligodendrocyte progenitor cells (OPCs) undergo marked morphological changes to become mature oligodendrocytes, but the metabolic resources for this process have not been fully elucidated. Although lactate, a metabolic derivative of glycogen, has been reported to be consumed in oligodendrocytes as a metabolite, and to ameliorate hypomyelination induced by low glucose conditions, it is not clear about the direct contribution of lactate to cell cycling and differentiation of OPCs, and the source of lactate for remyelination. Therefore, we evaluated the effect of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB), an inhibitor of the glycogen catabolic enzyme glycogen phosphorylase, in a mouse cuprizone model. Cuprizone induced demyelination in the corpus callosum and remyelination occurred after cuprizone treatment ceased. This remyelination was inhibited by the administration of DAB. To further examine whether lactate affects proliferation or differentiation of OPCs, we cultured mouse primary OPC-rich cells and analyzed the effect of lactate. Lactate rescued the slowed cell cycling induced by 0.4 mM glucose, as assessed by the BrdU-positive cell ratio. Lactate also promoted OPC differentiation detected by monitoring the mature oligodendrocyte marker myelin basic protein, in the presence of both 36.6 mM and 0.4 mM glucose. Furthermore, these lactate-mediated effects were suppressed by the reported monocarboxylate transporter inhibitor, α-cyano-4-hydroxy-cinnamate. These results suggest that lactate directly promotes the cell cycling rate and differentiation of OPCs, and that glycogen, one of the sources of lactate, contributes to remyelination in vivo. J. Cell. Physiol. 232: 986-995, 2017. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

  15. Oligodendrocyte Progenitor Cells Directly Utilize Lactate for Promoting Cell Cycling and Differentiation

    PubMed Central

    Ichihara, Yoshinori; Doi, Toru; Ryu, Youngjae; Nagao, Motoshi; Sawada, Yasuhiro

    2016-01-01

    Oligodendrocyte progenitor cells (OPCs) undergo marked morphological changes to become mature oligodendrocytes, but the metabolic resources for this process have not been fully elucidated. Although lactate, a metabolic derivative of glycogen, has been reported to be consumed in oligodendrocytes as a metabolite, and to ameliorate hypomyelination induced by low glucose conditions, it is not clear about the direct contribution of lactate to cell cycling and differentiation of OPCs, and the source of lactate for remyelination. Therefore, we evaluated the effect of 1,4‐dideoxy‐1,4‐imino‐d‐arabinitol (DAB), an inhibitor of the glycogen catabolic enzyme glycogen phosphorylase, in a mouse cuprizone model. Cuprizone induced demyelination in the corpus callosum and remyelination occurred after cuprizone treatment ceased. This remyelination was inhibited by the administration of DAB. To further examine whether lactate affects proliferation or differentiation of OPCs, we cultured mouse primary OPC‐rich cells and analyzed the effect of lactate. Lactate rescued the slowed cell cycling induced by 0.4 mM glucose, as assessed by the BrdU‐positive cell ratio. Lactate also promoted OPC differentiation detected by monitoring the mature oligodendrocyte marker myelin basic protein, in the presence of both 36.6 mM and 0.4 mM glucose. Furthermore, these lactate‐mediated effects were suppressed by the reported monocarboxylate transporter inhibitor, α‐cyano‐4‐hydroxy‐cinnamate. These results suggest that lactate directly promotes the cell cycling rate and differentiation of OPCs, and that glycogen, one of the sources of lactate, contributes to remyelination in vivo. J. Cell. Physiol. 232: 986–995, 2017. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:27861886

  16. Galactose promotes fat mobilization in obese lactating and non-lactating women

    USDA-ARS?s Scientific Manuscript database

    Galactose consumption results in a lower rise in plasma glucose and insulin concentrations when compared to glucose. The lower insulin might promote lipolysis during meal absorption. An isocaloric galactose drink, when compared to glucose, will sustain fat mobilization during meal consumption while...

  17. Galactose promotes fat mobilization in obese lactating and nonlactating women

    USDA-ARS?s Scientific Manuscript database

    Galactose consumption as the only carbohydrate source, results in little increase in plasma glucose and insulin concentrations when compared with fasting. Lower insulin might promote endogenous lipolysis during meal absorption, which may facilitate fat loss. The objective was to test the hypothesis ...

  18. Dietary lycopene and tomato extract supplementations inhibit nonalcoholic steatohepatitis-promoted hepatocarcinogenesis in rats

    USDA-ARS?s Scientific Manuscript database

    Epidemiological and experimental studies provide supportive evidence that lycopene (LY), a major carotenoid from tomatoes and tomato products, may act as a chemopreventive agent against certain types of cancers. We recently showed that high-fat diet (HFD)-induced nonalcoholic steatohepatitis (NASH) ...

  19. Increased Nitroxidative Stress Promotes Mitochondrial Dysfunction in Alcoholic and Nonalcoholic Fatty Liver Disease

    PubMed Central

    Song, Byoung-Joon; Abdelmegeed, Mohamed A.; Henderson, Lauren E.; Yoo, Seong-Ho; Wan, Jie; Purohit, Vishnudutt; Hardwick, James P.; Moon, Kwan-Hoon

    2013-01-01

    Increased nitroxidative stress causes mitochondrial dysfunctions through oxidative modifications of mitochondrial DNA, lipids, and proteins. Persistent mitochondrial dysfunction sensitizes the target cells/organs to other pathological risk factors and thus ultimately contributes to the development of more severe disease states in alcoholic and nonalcoholic fatty liver disease. The incidences of nonalcoholic fatty liver disease continuously increase due to high prevalence of metabolic syndrome including hyperlipidemia, hypercholesterolemia, obesity, insulin resistance, and diabetes. Many mitochondrial proteins including the enzymes involved in fat oxidation and energy supply could be oxidatively modified (including S-nitrosylation/nitration) under increased nitroxidative stress and thus inactivated, leading to increased fat accumulation and ATP depletion. To demonstrate the underlying mechanism(s) of mitochondrial dysfunction, we employed a redox proteomics approach using biotin-N-maleimide (biotin-NM) as a sensitive biotin-switch probe to identify oxidized Cys residues of mitochondrial proteins in the experimental models of alcoholic and acute liver disease. The aims of this paper are to briefly describe the mechanisms, functional consequences, and detection methods of mitochondrial dysfunction. We also describe advantages and limitations of the Cys-targeted redox proteomics method with alternative approaches. Finally, we discuss various applications of this method in studying oxidatively modified mitochondrial proteins in extrahepatic tissues or different subcellular organelles and translational research. PMID:23691267

  20. The promoting vibration in human heart lactate dehydrogenase is a preferred vibrational channel.

    PubMed

    Davarifar, Ardy; Antoniou, Dimitri; Schwartz, Steven D

    2011-12-29

    We examine whether the rate-promoting vibration of lactate dehydrogenase is a preferred axis of thermal energy transfer. While it seems plausible that such a mechanistically important motion is also a favored direction of energy transfer, none of the previous studies of rate-promoting vibrations in enzymatic catalysis have addressed this question. It is equally likely that the promoting vibration, though catalytically important, has no different properties than any other axis in the protein. Resolution of this issue is important for two reasons: First, if energy is transferred along this axis in a preferred fashion, it shows that the protein is engineered in a way that transfers thermal energy into a motion that is coupled to the chemical step. Second, the discovery of a preferred direction of thermal transfer provides a potential route to experimental verification of the promoting vibration concept. Our computational experiments are specifically designed to mimic potential laser experiment with the deposition of thermal energy in an active-site chromophore with subsequent measurement of temperature at various points in the protein. Our results indicate that the promoting vibration is indeed a preferred channel of energy transfer. In addition, we study the vibrational structure of the protein via the dynamical structure factor to show preferred vibrational motion along the promoting vibration axis is an inherent property of the protein structure via thermal fluctuations. © 2011 American Chemical Society

  1. Promoting Women’s Health in Hospitals: A Focus on Breastfeeding and Lactation Support for Employees and Patients

    PubMed Central

    Belay, Brook; Allen, Jessica; Williams, Nancy; Dooyema, Carrie; Foltz, Jennifer

    2015-01-01

    Hospitals often are one of the largest employers in communities, and nationwide, they employ more than 6.3 million employees. Hospitals also serve tens of millions of inpatients annually. Hospitals, therefore, can be leaders in worksite wellness and promoting breastfeeding and lactation support for new mothers. By adopting model standards and practices that promote breastfeeding, hospitals can influence women’s health. This article focuses on the efforts of the Centers for Disease Control and Prevention’s Division of Nutrition, Physical Activity, and Obesity to promote breastfeeding and lactation support for hospital employees and patients. PMID:23215865

  2. OXPHOS-Mediated Induction of NAD+ Promotes Complete Oxidation of Fatty Acids and Interdicts Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Nam, Minwoo; Lei, Shi; Cooper, Marcus P.

    2015-01-01

    OXPHOS is believed to play an important role in non-alcoholic fatty liver disease (NAFLD), however, precise mechanisms whereby OXPHOS influences lipid homeostasis are incompletely understood. We previously reported that ectopic expression of LRPPRC, a protein that increases cristae density and OXPHOS, promoted fatty acid oxidation in cultured primary hepatocytes. To determine the biological significance of that observation and define underlying mechanisms, we have ectopically expressed LRPPRC in mouse liver in the setting of NAFLD. Interestingly, ectopic expression of LRPPRC in mouse liver completely interdicted NAFLD, including inflammation. Consistent with mitigation of NAFLD, two markers of hepatic insulin resistance—ROS and PKCε activity—were both modestly reduced. As reported by others, improvement of NAFLD was associated with improved whole-body insulin sensitivity. Regarding hepatic lipid homeostasis, the ratio of NAD+ to NADH was dramatically increased in mouse liver replete with LRPPRC. Pharmacological activators and inhibitors of the cellular respiration respectively increased and decreased the [NAD+]/[NADH] ratio, indicating respiration-mediated control of the [NAD+]/[NADH] ratio. Supporting a prominent role for NAD+, increasing the concentration of NAD+ stimulated complete oxidation of fatty acids. Importantly, NAD+ rescued impaired fatty acid oxidation in hepatocytes deficient for either OXPHOS or SIRT3. These data are consistent with a model whereby augmented hepatic OXPHOS increases NAD+, which in turn promotes complete oxidation of fatty acids and protects against NAFLD. PMID:25933096

  3. p16 deficiency promotes nonalcoholic steatohepatitis via regulation of hepatic oxidative stress.

    PubMed

    Lv, Fangqiao; Wu, Jun; Miao, Dengshun; An, Wei; Wang, Yutong

    2017-03-10

    Nonalcoholic steatohepatitis (NASH) is characterized by excess accumulation of lipids in liver, accompanied with hepatocyte injury, cell death and inflammation. Although p16 is known as tumor suppressor in multiple cancer types, it remains unclear whether p16 plays a critical role in NASH. To determine whether p16 could play a role in the pathogenesis of NASH, wild-type mice and p16(-/-) mice were fed on a methionine and choline-deficient (MCD) diet for 3 weeks, and liver steatosis, fibrosis, and inflammation were evaluated. Our data show that p16(-/-) mice fed with MCD diet displayed more significant hepatic steatosis, hepatocyte damage, increased oxidative stress and inflammatory cell infiltration compared to MCD-fed WT mice. It was also clear that the increased ROS and the accumulation of lipid in BEL-7402 cells occurred when p16 expression was depleted with siRNA. These findings indicate that p16 may play a critical role in the development of NASH by reining in ROS production and by inhabiting inflammatory response.

  4. High dietary fat intake during lactation promotes development of diet-induced obesity in male offspring of mice.

    PubMed

    Tsuduki, Tsuyoshi; Kitano, Yasuna; Honma, Taro; Kijima, Ryo; Ikeda, Ikuo

    2013-01-01

    The maternal nutritional status during pregnancy and lactation influences the risk of obesity in offspring, but the details of this phenomenon are unclear. In particular, there is little information on the influence on the offspring of the maternal nutritional status during lactation only. Therefore, in this study, we examined the influence of high dietary fat intake in dams during lactation on the risk of obesity in offspring, using C57BL/6J mice. The mice were fed a control diet (CD) during pregnancy. After birth, dams were fed a CD or a high-fat diet (HD) during lactation (3 wk). Fat and energy were significantly increased in milk from dams fed a HD during lactation. Male offspring were weaned at 3 wk old and fed a CD for 4 wk, which resulted in no significant difference in their physique. Four weeks after weaning, the offspring (7 wk old) were fed a CD or HD for 4 wk to induce obesity. High dietary fat intake in dams and offspring promoted lipid accumulation in white adipose tissue and adipocyte hypertrophy in male offspring. The underlying mechanism may involve an increase in expression of Lpl and a decrease in expression of Hsl in white adipose tissue of offspring. In conclusion, our results show that high dietary fat intake during lactation promotes development of diet-induced obesity in male offspring.

  5. Myeloperoxidase–Hepatocyte–Stellate Cell Cross Talk Promotes Hepatocyte Injury and Fibrosis in Experimental Nonalcoholic Steatohepatitis

    PubMed Central

    Pulli, Benjamin; Ali, Muhammad; Iwamoto, Yoshiko; Zeller, Matthias W.G.; Schob, Stefan; Linnoila, Jenny J.

    2015-01-01

    Abstract Aims: Myeloperoxidase (MPO), a highly oxidative enzyme secreted by leukocytes has been implicated in human and experimental nonalcoholic steatohepatitis (NASH), but the underlying mechanisms remain unknown. In this study, we investigated how MPO contributes to progression from steatosis to NASH. Results: In C57Bl/6J mice fed a diet deficient in methionine and choline to induce NASH, neutrophils and to a lesser extent inflammatory monocytes are markedly increased compared with sham mice and secrete abundant amounts of MPO. Through generation of HOCl, MPO directly causes hepatocyte death in vivo. In vitro experiments demonstrate mitochondrial permeability transition pore induction via activation of SAPK/JNK and PARP. MPO also contributes to activation of hepatic stellate cells (HSCs), the most important source of collagen in the liver. In vitro MPO-activated HSCs have an activation signature (MAPK and PI3K-AKT phosphorylation) and upregulate COL1A1, α-SMA, and CXCL1. MPO-derived oxidative stress also activates transforming growth factor β (TGF-β) in vitro, and TGF-β signaling inhibition with SB-431542 decreased steatosis and fibrosis in vivo. Conversely, congenital absence of MPO results in reduced hepatocyte injury, decreased levels of TGF-β, fewer activated HSCs, and less severe fibrosis in vivo. Innovation and Conclusion: Cumulatively, these findings demonstrate important cross talk between inflammatory myeloid cells, hepatocytes, and HSCs via MPO and establish MPO as part of a proapoptotic and profibrotic pathway of progression in NASH, as well as a potential therapeutic target to ameliorate this disease. Antioxid. Redox Signal. 23, 1255–1269. PMID:26058518

  6. From efficacy to effectiveness: selecting indicators for a community-based lactational amenorrhoea method promotion programme.

    PubMed

    Bender, D E; Dusch, E; McCann, M F

    1998-04-01

    This paper reviews the results of clinical trials and community studies of lactational amenorrhoea and its role as a contraceptive method (LAM). Indicators which are used in efficacy trials and effectiveness interventions are compared and sets of indicators of effectiveness appropriate to community-based LAM programmes are recommended. A five-tiered ecological framework is used to facilitate selection of indicators which range from individual to policy level outcomes. The indicator framework is intended as a tool for health practitioners in family planning and maternal and child health service delivery settings who are interested in designing programmatic interventions for the promotion of LAM, particularly among less well-educated women of lower socioeconomic communities.

  7. Lactate promotes PGE2 synthesis and gluconeogenesis in monocytes to benefit the growth of inflammation-associated colorectal tumor

    PubMed Central

    Wei, Libin; Zhou, Yuxin; Yao, Jing; Qiao, Chen; Ni, Ting; Guo, Ruichen; Guo, Qinglong; Lu, Na

    2015-01-01

    Reprogramming energy metabolism, such as enhanced glycolysis, is an Achilles' heel in cancer treatment. Most studies have been performed on isolated cancer cells. Here, we studied the energy-transfer mechanism in inflammatory tumor microenvironment. We found that human THP-1 monocytes took up lactate secreted from tumor cells through monocarboxylate transporter 1. In THP-1 monocytes, the oxidation product of lactate, pyruvate competed with the substrate of proline hydroxylase and inhibited its activity, resulting in the stabilization of HIF-1α under normoxia. Mechanistically, activated hypoxia-inducible factor 1-α in THP-1 monocytes promoted the transcriptions of prostaglandin-endoperoxide synthase 2 and phosphoenolpyruvate carboxykinase, which were the key enzyme of prostaglandin E2 synthesis and gluconeogenesis, respectively, and promote the growth of human colon cancer HCT116 cells. Interestingly, lactate could not accelerate the growth of colon cancer directly in vivo. Instead, the human monocytic cells affected by lactate would play critical roles to ‘feed’ the colon cancer cells. Thus, recycling of lactate for glucose regeneration was reported in cancer metabolism. The anabolic metabolism of monocytes in inflammatory tumor microenvironment may be a critical event during tumor development, allowing accelerated tumor growth. PMID:25938544

  8. A 470 bp WAP-promoter fragment confers lactation independent, progesterone regulated mammary-specific gene expression in transgenic mice.

    PubMed

    Lipnik, Karoline; Petznek, Helga; Renner-Müller, Ingrid; Egerbacher, Monika; Url, Angelika; Salmons, Brian; Günzburg, Walter H; Hohenadl, Christine

    2005-04-01

    The ability of a 470 bp sub-fragment of the murine whey acidic protein (WAP) promoter in the context of a retroviral expression plasmid to direct gene expression to mammary epithelial cells was analysed in a number of independent transgenic mouse lines. In contrast to previous findings with the genuine 2.5 kb promoter fragment, our studies revealed a highly mammary gland-specific expression detectable only in non-lactating animals. This suggested a mainly progesterone-regulated activity of the short fragment. Therefore, transgene expression was examined in the progesterone-determined estrous cycle and during pregnancy. In accordance with in vitro data from stably transfected cell lines, in both situations expression was upregulated at stages associated with high progesterone levels. Taken together these data provide deeper insight into WAP-promoter regulation and stress the usefulness of the shortened fragment for a lactation independent mammary-targeted expression.

  9. The Comparative Effects of Sports Massage, Active Recovery, and Rest in Promoting Blood Lactate Clearance After Supramaximal Leg Exercise

    PubMed Central

    Martin, Nancy A.; Zoeller, Robert F.; Robertson, Robert J.; Lephart, Scott M.

    1998-01-01

    Objective: To determine the comparative effect of sports massage, active recovery, and rest on promoting blood lactate clearance after maximal anaerobic (supramaximal) leg exercise. Design and Setting: A counterbalanced experimental design with repeated measures was used. The repeated measures were the three treatment conditions. The order of the conditions was determined by random assignment to a counterbalanced test sequence. All data were collected in the Human Energy Research Laboratory at the University of Pittsburgh. Subjects: Ten male competitive cyclists volunteered for this investigation. Measurements: Serial venous blood samples were drawn and analyzed for blood lactate concentration for each test condition. Results: There were significant main effects for both absolute and relative values of blood lactate concentration between the three treatment groups and across time within groups. Conclusions: After supramaximal leg exercise, active recovery produced significant decreases in both absolute and relative measures of blood lactate concentration when compared with the sports massage and rest conditions. No significant difference was found between sports massage and rest for either absolute or relative changes in blood lactate concentration. PMID:16558481

  10. Gibberellic acid promoting phytic acid degradation in germinating soybean under calcium lactate treatment.

    PubMed

    Hui, Qianru; Wang, Mian; Wang, Pei; Ma, Ya; Gu, Zhenxin; Yang, Runqiang

    2017-06-30

    Phytic acid as a phosphorus storage vault provides phosphorus for plant development. It is an anti-nutritional factor for humans and some animals. However, its degradation products lower inositol phosphates have positive effects on human health. In this study, the effect of gibberellic acid (GA) on phytic acid degradation under calcium lactate (Ca) existence was investigated. The results showed that Ca + GA treatment promoted the growth status, hormone metabolism and phytic acid degradation in germinating soybean. At the same time, the availability of phosphorus, the activity of phytic acid degradation-associated enzyme and phosphoinositide-specific phospholipase C (PI-PLC) increased. However, the relative genes expression of phytic acid degradation-associated enzymes did not vary in accordance with their enzymes activity. The results revealed that GA could mediate the transport and function of calcium and a series of physiological and biochemical changes to regulate phytic acid degradation of soybean sprouts. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  11. The demands of lactation promote differential regulation of lipid stores in fasting elephant seals.

    PubMed

    Fowler, Melinda A; Debier, Cathy; Champagne, Cory D; Crocker, Daniel E; Costa, Daniel P

    2016-01-01

    Fasting animals must ration stored reserves appropriately for metabolic demands. Animals that experience fasting concomitant with other metabolically demanding activities are presented with conflicting demands of energy conservation and expenditure. Our objective was to understand how fasting northern elephant seals regulate the mobilization of lipid reserves and subsequently milk lipid content during lactation. We sampled 36 females early and 39 at the end of lactation. To determine the separate influences of lactation from fasting, we also sampled fasting but non-lactating females early and late (8 and 6 seals, respectively) in their molting fasting period. Mass and adiposity were measured, as well as circulating non-esterified fatty acid (NEFA), triacylglycerol (TAG), cortisol, insulin and growth hormone levels. Milk was collected from lactating females. Milk lipid content increased from 31% in early to 51% in late lactation. In lactating females plasma NEFA was positively related to cortisol and negatively related to insulin, but in molting seals, only variation in cortisol was related to NEFA. Milk lipid content varied with mass, adiposity, NEFA, TAG, cortisol and insulin. Surprisingly, growth hormone concentration was not related to lipid metabolites or milk lipid. Suppression of insulin release appears to be the differential regulator of lipolysis in lactating versus molting seals, facilitating mobilization of stored lipids and maintenance of high NEFA concentrations for milk synthesis. Milk lipid was strongly impacted by the supply of substrate to the mammary gland, indicating regulation at the level of mobilization of lipid reserves. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Nocturnal hypoxia-induced oxidative stress promotes progression of pediatric non-alcoholic fatty liver disease.

    PubMed

    Sundaram, Shikha S; Halbower, Ann; Pan, Zhaoxing; Robbins, Kristen; Capocelli, Kelley E; Klawitter, Jelena; Shearn, Colin T; Sokol, Ronald J

    2016-09-01

    Oxidative stress is proposed as a central mediator in NAFLD pathogenesis, but the specific trigger for reactive oxygen species generation has not been clearly delineated. In addition, emerging evidence shows that obesity related obstructive sleep apnea (OSA) and nocturnal hypoxia are associated with NAFLD progression in adults. The aim of this study was to determine if OSA/nocturnal hypoxia-induced oxidative stress promotes the progression of pediatric NAFLD. Subjects with biopsy proven NAFLD and lean controls were studied. Subjects underwent polysomnograms, liver histology scoring, laboratory testing, urine F(2)-isoprostanes (measure of lipid peroxidation) and 4-hydroxynonenal liver immunohistochemistry (in situ hepatic lipid peroxidation). We studied 36 adolescents with NAFLD and 14 lean controls. The OSA/hypoxia group (69% of NAFLD subjects) had more severe fibrosis (64% stage 0-2; 36% stage 3) than those without OSA/hypoxia (100% stage 0-2), p=0.03. Higher F(2)-isoprostanes correlated with apnea/hypoxia index (r=0.39, p=0.03), % time SaO2 <90% (r=0.56, p=0.0008) and inversely with SaO2 nadir (r=-0.46, p=0.008). OSA/hypoxia was most severe in subjects with the greatest 4HNE staining (p=0.03). Increasing F(2)-isoprostanes(r=0.32, p=0.04) and 4HNE hepatic staining (r=0.47, p=0.007) were associated with worsening steatosis. Greater oxidative stress occurred in subjects with definite NASH as measured by F(2)-isoprostanes (p=0.06) and hepatic 4HNE (p=0.03) compared to those with borderline/not NASH. These data support the role of nocturnal hypoxia as a trigger for localized hepatic oxidative stress, an important factor associated with the progression of NASH and hepatic fibrosis in obese pediatric patients. Obstructive sleep apnea and low nighttime oxygen are associated with NAFLD progression in adults. In this study, we show that adolescents with NAFLD who have OSA and low oxygen have significant scar tissue in their livers. NAFLD subjects affected by OSA and low

  13. High Dietary Fat Intake during Lactation Promotes the Development of Social Stress-Induced Obesity in the Offspring of Mice.

    PubMed

    Tsuduki, Tsuyoshi; Yamamoto, Kazushi; E, Shuang; Hatakeyama, Yu; Sakamoto, Yu

    2015-07-17

    This study examined how a maternal high-fat diet (HD) during lactation and exposure of offspring to isolation stress influence the susceptibility of offspring to the development of obesity. C57BL/6J mice were fed a commercial diet (CD) during pregnancy and a CD or HD during lactation. Male offspring were weaned at three weeks of age, fed a CD until seven weeks of age, and fed a CD or HD until 11 weeks of age. Offspring were housed alone (isolation stress) or at six per cage (ordinary circumstances). Thus, offspring were assigned to one of eight groups: dams fed a CD or HD during lactation and offspring fed a CD or HD and housed under ordinary circumstances or isolation stress. Serum corticosterone level was significantly elevated by isolation stress. High-fat feeding of offspring reduced their serum corticosterone level, which was significantly elevated by a maternal HD. A maternal HD and isolation stress had combined effects in elevating the serum corticosterone level. These findings suggest that a maternal HD during lactation enhances the stress sensitivity of offspring. White adipose tissue weights were significantly increased by a maternal HD and isolation stress and by their combination. In addition, significant adipocyte hypertrophy was induced by a maternal HD and isolation stress and exacerbated by their combination. Thus, a maternal HD and isolation stress promote visceral fat accumulation and adipocyte hypertrophy, accelerating the progression of obesity through their combined effects. The mechanism may involve enhanced fatty acid synthesis and lipid influx from blood into adipose tissue. These findings demonstrate that a maternal HD during lactation may increase the susceptibility of offspring to the development of stress-induced obesity.

  14. Comparison between a pediatric health promotion center and a pediatric obesity clinic in detecting metabolic syndrome and non-alcoholic fatty liver disease in children.

    PubMed

    Yang, Hye Ran; Yi, Dae Yong; Choi, Hyoung Soo

    2014-12-01

    This study was done to evaluate the efficacy of health check-ups in children in detecting metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) by comparing the pediatric health promotion center with the pediatric obesity clinic. Children who visited a pediatric health promotion center (n=218) or a pediatric obesity clinic (n=178) were included. Anthropometric data, blood pressure, laboratory tests, and abdominal ultrasonography were evaluated. Two different criteria were applied to diagnose metabolic syndrome. The prevalence of metabolic syndrome in the 2 units was 3.2%-3.7% in a pediatric health promotion center and 23%-33.2% in a pediatric obesity clinic. Significant differences were observed in the prevalence of each component of metabolic syndrome between the 2 units including abdominal adiposity, blood pressure, serum triglycerides, and fasting blood glucose (P<0.05). The prevalence of NAFLD was 8.7% and 71.9% in the 2 units according to liver enzymes and 5.9% and 61.8% according to ultrasonography (P<0.05). The prevalence of metabolic syndrome and NAFLD was higher among patients visiting the obesity clinic targeting obese children than that among patients visiting the health promotion center offering routine check-ups. An obesity-oriented approach is required to prevent obesity-related health problems in children.

  15. Medium-chain fatty acids inhibit mitochondrial metabolism in astrocytes promoting astrocyte-neuron lactate and ketone body shuttle systems.

    PubMed

    Thevenet, Jonathan; De Marchi, Umberto; Domingo, Jaime Santo; Christinat, Nicolas; Bultot, Laurent; Lefebvre, Gregory; Sakamoto, Kei; Descombes, Patrick; Masoodi, Mojgan; Wiederkehr, Andreas

    2016-05-01

    Medium-chain triglycerides have been used as part of a ketogenic diet effective in reducing epileptic episodes. The health benefits of the derived medium-chain fatty acids (MCFAs) are thought to result from the stimulation of liver ketogenesis providing fuel for the brain. We tested whether MCFAs have direct effects on energy metabolism in induced pluripotent stem cell-derived human astrocytes and neurons. Using single-cell imaging, we observed an acute pronounced reduction of the mitochondrial electrical potential and a concomitant drop of the NAD(P)H signal in astrocytes, but not in neurons. Despite the observed effects on mitochondrial function, MCFAs did not lower intracellular ATP levels or activate the energy sensor AMP-activated protein kinase. ATP concentrations in astrocytes were unaltered, even when blocking the respiratory chain, suggesting compensation through accelerated glycolysis. The MCFA decanoic acid (300 μM) promoted glycolysis and augmented lactate formation by 49.6%. The shorter fatty acid octanoic acid (300 μM) did not affect glycolysis but increased the rates of astrocyte ketogenesis 2.17-fold compared with that of control cells. MCFAs may have brain health benefits through the modulation of astrocyte metabolism leading to activation of shuttle systems that provide fuel to neighboring neurons in the form of lactate and ketone bodies.-Thevenet, J., De Marchi, U., Santo Domingo, J., Christinat, N., Bultot, L., Lefebvre, G., Sakamoto, K., Descombes, P., Masoodi, M., Wiederkehr, A. Medium-chain fatty acids inhibit mitochondrial metabolism in astrocytes promoting astrocyte-neuron lactate and ketone body shuttle systems.

  16. The Role of Morbid Obesity in the Promotion of Metabolic Disruptions and Non-Alcoholic Steatohepatitis by Helicobacter Pylori

    PubMed Central

    Valladares, Silvia; López-Cano, Carolina; Gutiérrez, Liliana; Ciudin, Andreea; Fort, José Manuel; Reñé, Josep Maria; Matias-Guiu, Xavier; de Torres, Inés; Bueno, Marta; Pallarés, Judit; Baena, Juan Antonio

    2016-01-01

    Background Helicobacter pylory (HP) infection has been associated to an increased rate of type 2 diabetes (T2D) and liver disease through its effect on insulin resistance and systemic inflammation. However, results are inconstant and no studies exist in morbidly obese patients, in which both insulin resistance and inflammation coexist. Material and Methods Cross-sectional study to evaluate the relationship between HP infection and alterations in carbohydrate metabolism, lipid profile, inflammation markers, and liver disease in patients awaiting for bariatric surgery. HP infection was histologically assessed in gastric antrum biopsy from 416 subjects. Liver biopsy was also available in 93 subjects. Results Both impaired fasting glucose and T2D were similar when comparing subjects with and without HP infection (24.2% vs. 22%, p = 0.290 and 29.4% vs. 29.1%, p = 0.916, respectively), with no differences between groups in the HOMA-IR, lipid profile neither inflammatory parameters. However, HP infection was higher among subjects with a BMI ≥ 40.0 kg/m2 in comparison with lower degrees of obesity (71.7% vs. 60.0%, p = 0.041). In addition, subjects without HP infection showed higher degrees of steatosis (44.1±26.4% vs. 32.0±20.7%, p = 0.038), as well as a lower prevalence of non-alcoholic steatohepatitis (9.3% vs. 30.7%, p = 0.023). Conclusions In patients with morbid obesity, HP infection does not seem to be associated with abnormal carbohydrate metabolism. In addition, less advanced degrees of non-alcoholic fatty disease were observed. We suggest that low-grade inflammation that accompanies obesity mitigates the diabetogenic effect of HP, so the presence of obesity should be considered in studies that evaluate the HP metabolic effects. PMID:27893763

  17. The Role of Morbid Obesity in the Promotion of Metabolic Disruptions and Non-Alcoholic Steatohepatitis by Helicobacter Pylori.

    PubMed

    Lecube, Albert; Valladares, Silvia; López-Cano, Carolina; Gutiérrez, Liliana; Ciudin, Andreea; Fort, José Manuel; Reñé, Josep Maria; Matias-Guiu, Xavier; de Torres, Inés; Bueno, Marta; Pallarés, Judit; Baena, Juan Antonio

    2016-01-01

    Helicobacter pylory (HP) infection has been associated to an increased rate of type 2 diabetes (T2D) and liver disease through its effect on insulin resistance and systemic inflammation. However, results are inconstant and no studies exist in morbidly obese patients, in which both insulin resistance and inflammation coexist. Cross-sectional study to evaluate the relationship between HP infection and alterations in carbohydrate metabolism, lipid profile, inflammation markers, and liver disease in patients awaiting for bariatric surgery. HP infection was histologically assessed in gastric antrum biopsy from 416 subjects. Liver biopsy was also available in 93 subjects. Both impaired fasting glucose and T2D were similar when comparing subjects with and without HP infection (24.2% vs. 22%, p = 0.290 and 29.4% vs. 29.1%, p = 0.916, respectively), with no differences between groups in the HOMA-IR, lipid profile neither inflammatory parameters. However, HP infection was higher among subjects with a BMI ≥ 40.0 kg/m2 in comparison with lower degrees of obesity (71.7% vs. 60.0%, p = 0.041). In addition, subjects without HP infection showed higher degrees of steatosis (44.1±26.4% vs. 32.0±20.7%, p = 0.038), as well as a lower prevalence of non-alcoholic steatohepatitis (9.3% vs. 30.7%, p = 0.023). In patients with morbid obesity, HP infection does not seem to be associated with abnormal carbohydrate metabolism. In addition, less advanced degrees of non-alcoholic fatty disease were observed. We suggest that low-grade inflammation that accompanies obesity mitigates the diabetogenic effect of HP, so the presence of obesity should be considered in studies that evaluate the HP metabolic effects.

  18. A lactate electrochemical biosensor with a titanate nanotube as direct electron transfer promoter

    NASA Astrophysics Data System (ADS)

    Yang, Mingli; Wang, Jin; Li, Huaqing; Zheng, Jian-Guo; Wu, Nianqiang Nick

    2008-02-01

    Hydrogen titanate (H2Ti3O7) nanotubes (TNTs) have been synthesized by a one-step hydrothermal processing. Lactate oxidase (LOx) enzyme has been immobilized on the three-dimensional porous TNT network to make an electrochemical biosensor for lactate detection. Cyclic voltammetry and amperometry tests reveal that the LOx enzyme, which is supported on TNTs, maintains their substrate-specific catalytic activity. The nanotubes offer the pathway for direct electron transfer between the electrode surface and the active redox centers of LOx, which enables the biosensor to operate at a low working potential and to avoid the influence of the presence of O2 on the amperometric current response. The biosensor exhibits a sensitivity of 0.24 µA cm-2 mM-1, a 90% response time of 5 s, and a linear response in the range from 0.5 to 14 mM and the redox center of enzyme obviates the need of redox mediators for electrochemical enzymatic sensors, which is attractive for the development of reagentless biosensors.

  19. Lactate Dehydrogenase-B Is Silenced by Promoter Methylation in a High Frequency of Human Breast Cancers

    PubMed Central

    Brown, Nicola J.; Higham, Sue E.; Perunovic, Branko; Arafa, Mohammad; Balasubramanian, Sabapathy; Rehman, Ishtiaq

    2013-01-01

    Objective Under normoxia, non-malignant cells rely on oxidative phosphorylation for their ATP production, whereas cancer cells rely on Glycolysis; a phenomenon known as the Warburg effect. We aimed to elucidate the mechanisms contributing to the Warburg effect in human breast cancer. Experimental design Lactate Dehydrogenase (LDH) isoenzymes were profiled using zymography. LDH-B subunit expression was assessed by reverse transcription PCR in cells, and by Immunohistochemistry in breast tissues. LDH-B promoter methylation was assessed by sequencing bisulfite modified DNA. Results Absent or decreased expression of LDH isoenzymes 1-4, were seen in T-47D and MCF7 cells. Absence of LDH-B mRNA was seen in T-47D cells, and its expression was restored following treatment with the demethylating agent 5'Azacytadine. LDH-B promoter methylation was identified in T-47D and MCF7 cells, and in 25/ 25 cases of breast cancer tissues, but not in 5/ 5 cases of normal breast tissues. Absent immuno-expression of LDH-B protein (<10% cells stained), was seen in 23/ 26 (88%) breast cancer cases, and in 4/8 cases of adjacent ductal carcinoma in situ lesions. Exposure of breast cancer cells to hypoxia (1% O2), for 48 hours resulted in significant increases in lactate levels in both MCF7 (14.0 fold, p = 0.002), and T-47D cells (2.9 fold, p = 0.009), but not in MDA-MB-436 (-0.9 fold, p = 0.229), or MCF10AT (1.2 fold, p = 0.09) cells. Conclusions Loss of LDH-B expression is an early and frequent event in human breast cancer occurring due to promoter methylation, and is likely to contribute to an enhanced glycolysis of cancer cells under hypoxia. PMID:23437403

  20. Epigenetic regulation of insulin resistance in nonalcoholic fatty liver disease: impact of liver methylation of the peroxisome proliferator-activated receptor γ coactivator 1α promoter.

    PubMed

    Sookoian, Silvia; Rosselli, Maria Soledad; Gemma, Carolina; Burgueño, Adriana L; Fernández Gianotti, Tomas; Castaño, Gustavo O; Pirola, Carlos J

    2010-12-01

    Insulin resistance (IR) and mitochondrial dysfunction play a central role in the pathophysiology of nonalcoholic fatty liver disease (NAFLD). We hypothesized that genetic factors and epigenetic modifications occurring in the liver contribute to the IR phenotype. We specifically examined whether fatty liver and IR are modified by hepatic DNA methylation of the peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A) and mitochondrial transcription factor A (TFAM) promoters, and also evaluated whether liver mitochondrial DNA (mtDNA) content is associated with NAFLD and IR. We studied liver biopsies obtained from NAFLD patients in a case-control design. After bisulfite treatment of DNA, we used methylation-specific polymerase chain reaction (PCR) to assess the putative methylation of three CpG in the PPARGC1A and TFAM promoters. Liver mtDNA quantification using nuclear DNA (nDNA) as a reference was evaluated by way of real-time PCR. Liver PPARGC1A methylated DNA/unmethylated DNA ratio correlated with plasma fasting insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR); TFAM methylated DNA/unmethylated DNA ratio was inversely correlated with insulin levels. PPARGC1A promoter methylation was inversely correlated with the abundance of liver PPARGC1A messenger RNA. The liver mtDNA/nDNA ratio was significantly higher in control livers compared with NAFLD livers. mtDNA/nDNA ratio was inversely correlated with HOMA-IR, fasting glucose, and insulin and was inversely correlated with PPARGC1A promoter methylation. Our data suggest that the IR phenotype and the liver transcriptional activity of PPARGC1A show a tight interaction, probably through epigenetic modifications. Decreased liver mtDNA content concomitantly contributes to peripheral IR. Copyright © 2010 American Association for the Study of Liver Diseases.

  1. Nicotine promotes Streptococcus mutans extracellular polysaccharide synthesis, cell aggregation and overall lactate dehydrogenase activity.

    PubMed

    Huang, R; Li, M; Gregory, R L

    2015-08-01

    Several epidemiology studies have reported a positive relationship between smoking and dental caries. Nicotine, an alkaloid component of tobacco, has been demonstrated to stimulate biofilm formation and metabolic activity of Streptococcus mutans, one of the most important pathogens of dental caries. The first aim of the present study was to explore the possible mechanisms leading to increased biofilm by nicotine treatment from three aspects, extracellular polysaccharides (EPS) synthesis, glucosyltransferase (Gtf) synthesis and glucan-binding protein (Gbp) synthesis at the mRNA and protein levels. The second aim was to investigate how nicotine affects S. mutans virulence, particular in lactate dehydrogenase (LDH) activity. Confocal laser scanning microscopy results demonstrated that both biofilm bacterial cell numbers and EPS were increased by nicotine. Gtf and GbpA protein expression of S. mutans planktonic cells were upregulated while GbpB protein expression of biofilm cells were downregulated by nicotine. The mRNA expression trends of those genes were mostly consistent with results on protein level but not statistically significant, and gtfD and gbpD of biofilm cells were inhibited. Nicotine was not directly involved in S. mutans LDH activity. However, since it increases the total number of bacterial cells in biofilm, the overall LDH activity of S. mutans biofilm is increased. In conclusion, nicotine stimulates S. mutans planktonic cell Gtf and Gbp expression. This leads to more planktonic cells attaching to the dental biofilm. Increased cell numbers within biofilm results in higher overall LDH activity. This contributes to caries development in smokers.

  2. Acetylation of Mitochondrial Trifunctional Protein α-Subunit Enhances Its Stability To Promote Fatty Acid Oxidation and Is Decreased in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Guo, Liang; Zhou, Shui-Rong; Wei, Xiang-Bo; Liu, Yuan; Chang, Xin-Xia; Liu, Yang; Ge, Xin; Dou, Xin; Huang, Hai-Yan; Qian, Shu-Wen; Li, Xi; Lei, Qun-Ying

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease, and decreased fatty acid oxidation is one of the important contributors to NAFLD. Mitochondrial trifunctional protein α-subunit (MTPα) functions as a critical enzyme for fatty acid β-oxidation, but whether dysregulation of MTPα is pathogenically connected to NAFLD is poorly understood. We show that MTPα is acetylated at lysine residues 350, 383, and 406 (MTPα-3K), which promotes its protein stability by antagonizing its ubiquitylation on the same three lysines (MTPα-3K) and blocking its subsequent degradation. Sirtuin 4 (SIRT4) has been identified as the deacetylase, deacetylating and destabilizing MTPα. Replacement of MTPα-3K with either MTPα-3KR or MTPα-3KQ inhibits cellular lipid accumulation both in free fatty acid (FFA)-treated alpha mouse liver 12 (AML12) cells and primary hepatocytes and in the livers of high-fat/high-sucrose (HF/HS) diet-fed mice. Moreover, knockdown of SIRT4 could phenocopy the effects of MTPα-3K mutant expression in mouse livers, and MTPα-3K mutants more efficiently attenuate SIRT4-mediated hepatic steatosis in HF/HS diet-fed mice. Importantly, acetylation of both MTPα and MTPα-3K is decreased while SIRT4 is increased in the livers of mice and humans with NAFLD. Our study reveals a novel mechanism of MTPα regulation by acetylation and ubiquitylation and a direct functional link of this regulation to NAFLD. PMID:27457618

  3. Long non-coding RNA LINK-A promotes glioma cell growth and invasion via lactate dehydrogenase A.

    PubMed

    Wu, Dejun; Zhao, Bing; Cao, Xiaoyu; Wan, Jinghai

    2017-09-01

    Long non-coding RNAs (lncRNAs) have recently been identified in mammals as new modulators of cancer origin and progression participating in various cellular pro-cesses. Long intergenic non-coding RNA for kinase activation (LINK-A), belonging to one of the intergenic lncRNAs, was reported to regulate signaling pathways correlated with triple-negative breast cancer. However, the expression and the functional role of LINK-A in glioma are still unclear. In the present study, we demonstrated that LINK-A was upregulated in human glioma cells compared with the expression noted in normal astrocytes. Knockdown of LINK-A inhibited cell proliferation, migration and invasion in U87 and U251 glioma cells. In addition, we found that lactate dehydrogenase A (LDH-A) was regulated by LINK-A, and enforced expression of LDH-A promoted glycolysis and proliferation in glioma cells. More importantly, we found that LDH-A was involved in the LINK-A-mediated proliferation and invasion of glioma cells. Collectively, these results provide new evidence of an important role for LINK-A in the development of glioma.

  4. [Lactational amenorrhea: nurses experience and the promotion of this alternative method of contraception].

    PubMed

    Moura, Escolástica Rejane Ferreira; de Freitas, Giselle Lima; Pinheiro, Ana Karina Bezerra; Machado, Márcia Maria Tavares; da Silva, Raimunda Magalhães; de Oliveira Lopes, Marcos Venicios

    2011-03-01

    This is a cross-sectional, field study that used a quantitative approach with the objectives to identify nurses' personal experiences with breastfeeding and with the Lactactional Amenorrhea Method (LAM); learn the reasons for not adhering to breastfeeding or adhering to mixed feeding; establish the relationship between nurses' personal experience with the LAM and their giving orientations about this contraceptive method to users of the Primary Health Care Center. Participants were 137 nurses with the Family Health Strategy in Fortaleza, Ceará, Brazil, and data collection was performed through interviews. Most participants were female; i.e., 121 participants (88.3%). The age range was 26 to 59 years, with an average of 38.3 years. Sixty-six participants (94.2%) had a previous experience with breastfeeding, 61 (92.4%) of which adhered to Exclusive Breastfeeding (EB), 5 (7.6%) to Mixed Feeding (MF); and 4 (5.8%) did not breastfeed. The time of EB ranged from one to six months, with an average 4.31 months. Twelve nurses (19.6%) followed the LAM. The study showed that the nurses' personal experience with the LAM did not affect the promotion of this method to the clientele that they assist.

  5. Ablation of systemic SIRT1 activity promotes nonalcoholic fatty liver disease by affecting liver-mesenteric adipose tissue fatty acid mobilization

    USDA-ARS?s Scientific Manuscript database

    The incidence of nonalcoholic fatty liver disease (NAFLD) is escalating paralleled with obesity rates in both adults and children. Mammalian sirtuin 1 (SIRT1), a highly conserved NAD+-dependent protein deacetylase, has been identified as a metabolic regulator of lipid homeostasis and a potential tar...

  6. Sodium selenite supplementation during pregnancy and lactation promotes anxiolysis and improves mnemonic performance in wistar rats' offspring.

    PubMed

    Laureano-Melo, Roberto; Império, Güínever Eustáquio do; da Silva-Almeida, Claudio; Kluck, George Eduardo Gabriel; Cruz Seara, Fernando de Azevedo; da Rocha, Fábio Fagundes; da Silveira, Anderson Luiz Bezerra; Reis, Luís Carlos; Ortiga-Carvalho, Tania Maria; da Silva Côrtes, Wellington

    2015-11-01

    Selenium is a micronutrient which is part of selenoprotein molecules and participates in a vast number of physiological roles and, among them,we have fetal and neonatal development. Therefore, the aimof this studywas to evaluate possible behavioral changes in offspring of female rats supplemented during pregnancy and lactation with sodium selenite. To address that, we treated two groups of female rats by saline or sodium selenite at a dose of 1mg/kg through oral route and performed neurochemical and behavioral tests. In the offspring, the thyroid profile and hippocampal neurochemistrywere evaluated. Behavioral testswere performed in pups both during childhood and adulthood. We found out that selenium (Se) supplementation increased serum levels of triiodothyronine (25%, p b 0.001) and thyroxine (18%, p b 0.05) and promoted a tryptophan hydroxylase 2 (TPH 2) expression decrease (17%, p b 0.01) and tyrosine hydroxylase (TH) expression increase (202%, p b 0.01) in the hippocampus. The cholinesterase activity was decreased (28%, p b 0.01) in Se supplemented rats, suggesting a neurochemical modulation in the hippocampal activity. During childhood, the Sesupplemented offspring had a reduction in anxiety-like behavior both in elevated plus maze test and in light–dark box test. In adulthood, Se-treated pups had an increase in the locomotor activity (36%, p b 0.05) and in rearing episodes (77%, p b 0.001) in the open field test, while in the elevated plus maze test they also exhibited an increase in the time spent in the open arms (243%, p b 0.01). For the object recognition test, Se-treated offspring showed increase in the absolute (230.16%, p b 0.05) and relative index discrimination (234%, p b 0.05). These results demonstrate that maternal supplementation by sodium selenite promoted psychobiological changes both during childhood and adulthood. Therefore, the behavioral profile observed possibly can be explained by neurochemical changes induced by thyroid hormones during

  7. Nonalcoholic Fatty Liver Disease.

    PubMed

    Thrasher, Tyler; Abdelmalek, Manal F

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, is the leading cause of chronic liver disease. Treatments target lifestyle modification and improvement of underlying risk factors. Noninvasive biomarkers for diagnosis and staging of NAFLD and safe, cost-effective treatments for patients with nonalcoholic steatohepatitis (NASH) and/or NASH-related cirrhosis are currently under investigation. ©2016 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.

  8. Lactate dehydrogenase A negatively regulated by miRNAs promotes aerobic glycolysis and is increased in colorectal cancer.

    PubMed

    Wang, Jian; Wang, Hui; Liu, Aifen; Fang, Changge; Hao, Jianguo; Wang, Zhenghui

    2015-08-14

    Reprogramming metabolism of tumor cells is a hallmark of cancer. Lactate dehydrogenase A (LDHA) is frequently overexpressed in tumor cells. Previous studies has shown higher levels of LDHA is related with colorectal cancer (CRC), but its role in tumor maintenance and underlying molecular mechanisms has not been established. Here, we investigated miRNAs-induced changes in LDHA expression. We reported that colorectal cancer express higher levels of LDHA compared with adjacent normal tissue. Knockdown of LDHA resulted in decreased lactate and ATP production, and glucose uptake. Colorectal cancer cells with knockdown of LDHA had much slower growth rate than control cells. Furthermore, we found that miR-34a, miR-34c, miR-369-3p, miR-374a, and miR-4524a/b target LDHA and regulate glycolysis in cancer cells. There is a negative correlation between these miRNAs and LDHA expression in colorectal cancer tissues. More importantly, we identified a genetic loci newly associated with increased colorectal cancer progression, rs18407893 at 11p15.4 (in 3'-UTR of LDHA), which maps to the seed sequence recognized by miR-374a. Cancer cells overexpressed miR-374a has decreased levels of LDHA compared with miR-374a-MUT (rs18407893 at 11p15.4). Taken together, these novel findings provide more therapeutic approaches to the Warburg effect and therapeutic targets of cancer energy metabolism.

  9. Hypoxia-responsive miR-210 promotes self-renewal capacity of colon tumor-initiating cells by repressing ISCU and by inducing lactate production

    PubMed Central

    Ullmann, Pit; Qureshi-Baig, Komal; Rodriguez, Fabien; Ginolhac, Aurélien; Nonnenmacher, Yannic; Ternes, Dominik; Weiler, Jil; Gäbler, Karoline; Bahlawane, Christelle; Hiller, Karsten; Haan, Serge; Letellier, Elisabeth

    2016-01-01

    Low oxygen concentrations (hypoxia) are known to affect the cellular metabolism and have been suggested to regulate a subpopulation of cancer cells with tumorigenic properties, the so-called tumor-initiating cells (TICs). To better understand the mechanism of hypoxia-induced TIC activation, we set out to study the role of hypoxia-responsive miRNAs in recently established colon cancer patient-derived TICs. We were able to show that low oxygen concentrations consistently lead to the upregulation of miR-210 in different primary TIC-enriched cultures. Both stable overexpression of miR-210 and knockdown of its target gene ISCU resulted in enhanced TIC self-renewal. We could validate the tumorigenic properties of miR- 210 in in vivo experiments by showing that ectopic expression of miR-210 results in increased tumor incidence. Furthermore, enhanced miR-210 expression correlated with reduced TCA cycle activity and increased lactate levels. Importantly, by blocking lactate production via inhibition of LDHA, we could reverse the promoting effect of miR-210 on self-renewal capacity, thereby emphasizing the regulatory impact of the glycolytic phenotype on colon TIC properties. Finally, by assessing expression levels in patient tissue, we could demonstrate the clinical relevance of the miR-210/ISCU signaling axis for colorectal carcinoma. Taken together, our study highlights the importance of hypoxia-induced miR-210 in the regulation of colon cancer initiation. PMID:27589845

  10. Hypoxia-responsive miR-210 promotes self-renewal capacity of colon tumor-initiating cells by repressing ISCU and by inducing lactate production.

    PubMed

    Ullmann, Pit; Qureshi-Baig, Komal; Rodriguez, Fabien; Ginolhac, Aurélien; Nonnenmacher, Yannic; Ternes, Dominik; Weiler, Jil; Gäbler, Karoline; Bahlawane, Christelle; Hiller, Karsten; Haan, Serge; Letellier, Elisabeth

    2016-10-04

    Low oxygen concentrations (hypoxia) are known to affect the cellular metabolism and have been suggested to regulate a subpopulation of cancer cells with tumorigenic properties, the so-called tumor-initiating cells (TICs). To better understand the mechanism of hypoxia-induced TIC activation, we set out to study the role of hypoxia-responsive miRNAs in recently established colon cancer patient-derived TICs. We were able to show that low oxygen concentrations consistently lead to the upregulation of miR-210 in different primary TIC-enriched cultures. Both stable overexpression of miR-210 and knockdown of its target gene ISCU resulted in enhanced TIC self-renewal. We could validate the tumorigenic properties of miR- 210 in in vivo experiments by showing that ectopic expression of miR-210 results in increased tumor incidence. Furthermore, enhanced miR-210 expression correlated with reduced TCA cycle activity and increased lactate levels. Importantly, by blocking lactate production via inhibition of LDHA, we could reverse the promoting effect of miR-210 on self-renewal capacity, thereby emphasizing the regulatory impact of the glycolytic phenotype on colon TIC properties. Finally, by assessing expression levels in patient tissue, we could demonstrate the clinical relevance of the miR-210/ISCU signaling axis for colorectal carcinoma. Taken together, our study highlights the importance of hypoxia-induced miR-210 in the regulation of colon cancer initiation.

  11. Biomimicry Promotes the Efficiency of a 10-Step Sequential Enzymatic Reaction on Nanoparticles, Converting Glucose to Lactate.

    PubMed

    Mukai, Chinatsu; Gao, Lizeng; Nelson, Jacquelyn L; Lata, James P; Cohen, Roy; Wu, Lauren; Hinchman, Meleana M; Bergkvist, Magnus; Sherwood, Robert W; Zhang, Sheng; Travis, Alexander J

    2017-01-02

    For nanobiotechnology to achieve its potential, complex organic-inorganic systems must grow to utilize the sequential functions of multiple biological components. Critical challenges exist: immobilizing enzymes can block substrate-binding sites or prohibit conformational changes, substrate composition can interfere with activity, and multistep reactions risk diffusion of intermediates. As a result, the most complex tethered reaction reported involves only 3 enzymes. Inspired by the oriented immobilization of glycolytic enzymes on the fibrous sheath of mammalian sperm, here we show a complex reaction of 10 enzymes tethered to nanoparticles. Although individual enzyme efficiency was higher in solution, the efficacy of the 10-step pathway measured by conversion of glucose to lactate was significantly higher when tethered. To our knowledge, this is the most complex organic-inorganic system described, and it shows that tethered, multi-step biological pathways can be reconstituted in hybrid systems to carry out functions such as energy production or delivery of molecular cargo.

  12. Mitochondrial oxidative stress in cancer-associated fibroblasts drives lactate production, promoting breast cancer tumor growth: understanding the aging and cancer connection.

    PubMed

    Balliet, Renee M; Capparelli, Claudia; Guido, Carmela; Pestell, Timothy G; Martinez-Outschoorn, Ubaldo E; Lin, Zhao; Whitaker-Menezes, Diana; Chiavarina, Barbara; Pestell, Richard G; Howell, Anthony; Sotgia, Federica; Lisanti, Michael P

    2011-12-01

    Increasing chronological age is the most significant risk factor for cancer. Recently, we proposed a new paradigm for understanding the role of the aging and the tumor microenvironment in cancer onset. In this model, cancer cells induce oxidative stress in adjacent stromal fibroblasts. This, in turn, causes several changes in the phenotype of the fibroblast including mitochondrial dysfunction, hydrogen peroxide production, and aerobic glycolysis, resulting in high levels of L-lactate production. L-lactate is then transferred from these glycolytic fibroblasts to adjacent epithelial cancer cells and used as "fuel" for oxidative mitochondrial metabolism.  Here, we created a new pre-clinical model system to directly test this hypothesis experimentally. To synthetically generate glycolytic fibroblasts, we genetically-induced mitochondrial dysfunction by knocking down TFAM using an sh-RNA approach.  TFAM is mitochondrial transcription factor A, which is important in functionally maintaining the mitochondrial respiratory chain. Interestingly, TFAM-deficient fibroblasts showed evidence of mitochondrial dysfunction and oxidative stress, with the loss of certain mitochondrial respiratory chain components, and the over-production of hydrogen peroxide and L-lactate. Thus, TFAM-deficient fibroblasts underwent metabolic reprogramming towards aerobic glycolysis.  Most importantly, TFAM-deficient fibroblasts significantly promoted tumor growth, as assayed using a human breast cancer (MDA-MB-231) xenograft model. These increases in glycolytic fibroblast driven tumor growth were independent of tumor angiogenesis. Mechanistically, TFAM-deficient fibroblasts increased the mitochondrial activity of adjacent epithelial cancer cells in a co-culture system, as seen using MitoTracker. Finally, TFAM-deficient fibroblasts also showed a loss of caveolin-1 (Cav-1), a known breast cancer stromal biomarker. Loss of stromal fibroblast Cav-1 is associated with early tumor recurrence, metastasis

  13. Synbiotics suppress the release of lactate dehydrogenase, promote non-specific immunity and integrity of jejunum mucosa in piglets.

    PubMed

    Andrejčáková, Zuzana; Sopková, Drahomíra; Vlčková, Radoslava; Kulichová, Lucia; Gancarčíková, Soňa; Almášiová, Viera; Holovská, Katarína; Petrilla, Vladimír; Krešáková, Lenka

    2016-09-01

    The aim of our experiment was to study how synbiotics are able to deal with the problems of post-weaning piglets. Lactobacillus plantarum - Biocenol(TM) LP96 (CCM 7512), Lactobacillus fermentum - Biocenol(TM) LF99 (CCM 7514) and flaxseed (rich in n-3 polyunsaturated fatty acids) were administered to 36 conventional piglets from a problematic breed with confirmed presence of enterotoxigenic Escherichia coli and Coronavirus. The experimental piglets were supplied with probiotic cheeses and crushed flax-seed in the period starting 10 days before weaning and lasting up to 14 days post-weaning. Piglets in the control group were supplied only control cheese. The impact of such additives on the release of lactate dehydrogenase (LDH; spectroscopic and electrophoretic assay), alteration of immunity (index of metabolic activity), jejunum histology (light microscopy), and health of conventional piglets from a problematic breed (monitoring of hematology, consistency and moisture of feces and body temperature) were examined. We found significant decrease in LDH leakage in the blood serum and tissue extracts, indicating better cell membrane integrity in the individual organs of animals. Probiotics and flaxseed applied together seem to be a good source of nutrients to improve the immune status and the integrity of jejunum mucosa during infection. © 2015 Japanese Society of Animal Science. © 2015 Japanese Society of Animal Science.

  14. Microvesicles released from fat-laden cells promote activation of hepatocellular NLRP3 inflammasome: A pro-inflammatory link between lipotoxicity and non-alcoholic steatohepatitis

    PubMed Central

    Bocca, Claudia; Foglia, Beatrice; Benetti, Elisa; Novo, Erica; Chiazza, Fausto; Rogazzo, Mara; Fantozzi, Roberto; Povero, Davide; Sutti, Salvatore; Bugianesi, Elisabetta; Feldstein, Ariel E.; Albano, Emanuele; Collino, Massimo; Parola, Maurizio

    2017-01-01

    Non-Alcoholic Fatty Liver Disease (NAFLD) is a major form of chronic liver disease in the general population in relation to its high prevalence among overweight/obese individuals and patients with diabetes type II or metabolic syndrome. NAFLD can progress to steatohepatitis (NASH), fibrosis and cirrhosis and end-stage of liver disease but mechanisms involved are still incompletely characterized. Within the mechanisms proposed to mediate the progression of NAFLD, lipotoxicity is believed to play a major role. In the present study we provide data suggesting that microvesicles (MVs) released by fat-laden cells undergoing lipotoxicity can activate NLRP3 inflammasome following internalization by either cells of hepatocellular origin or macrophages. Inflammasome activation involves NF-kB-mediated up-regulation of NLRP3, pro-caspase-1 and pro-Interleukin-1, then inflammasome complex formation and Caspase-1 activation leading finally to an increased release of IL-1β. Since the release of MVs from lipotoxic cells and the activation of NLRP3 inflammasome have been reported to occur in vivo in either clinical or experimental NASH, these data suggest a novel rational link between lipotoxicity and increased inflammatory response. PMID:28249038

  15. Lactation in Islam.

    PubMed

    Hefnawi, F I

    1982-01-01

    Preservation and promotion of breastfeeding in Islamic countries could be increased by stressing the religious importance of this practice as prescribed in Islamic religious teachings. The child's right to be breastfed is affirmed by the Quaran, the source of Islamic law and morality. Quranic verse 2:233 recommends a 2 year period of lactation. According to Islam a nursing mother is entitled to receive compensation from the father for nursing the child. The father, though, has the option to engage a paid or unpaid wet-nurse for the child, in which case the mother looses her right to be paid for nursing even is she volunteered to breastfeed. The mother's right to nurse a child without compensation is prior to a father's right to engage a wet-nurse. In another Islamic source the moral importance of breastfeeding is stressed. The mother receives the reward of a good deed for every single drop she gives her child. Islamic precepts on lactation influenced Arabian medicine. Avicenna's view that children should be breastfed for 2 years was approvingly quoted by European physicians in the 17th century. Major Arabian medical texts contain chapters on lactation, on tests for quality of breast milk, and on diets and drugs for improving lactation. Research at Al-Azhar University is directed toward finding a contraceptive that will not inhabit lactation and will not affect the quality of breast milk.

  16. The DNA damage checkpoint protein ATM promotes hepatocellular apoptosis and fibrosis in a mouse model of non-alcoholic fatty liver disease

    PubMed Central

    Daugherity, Erin K.; Balmus, Gabriel; Al Saei, Ahmed; Moore, Elizabeth S.; Abi Abdallah, Delbert; Rogers, Arlin B.; Weiss, Robert S.; Maurer, Kirk J.

    2012-01-01

    Steatoapoptosis is a hallmark of non-alcoholic fatty liver disease (NAFLD) and is an important factor in liver disease progression. We hypothesized that increased reactive oxygen species resulting from excess dietary fat contribute to liver disease by causing DNA damage and apoptotic cell death, and tested this by investigating the effects of feeding mice high fat or standard diets for 8 weeks. High fat diet feeding resulted in increased hepatic H2O2, superoxide production, and expression of oxidative stress response genes, confirming that the high fat diet induced hepatic oxidative stress. High fat diet feeding also increased hepatic steatosis, hepatitis and DNA damage as exemplified by an increase in the percentage of 8-hydroxyguanosine (8-OHG) positive hepatocytes in high fat diet fed mice. Consistent with reports that the DNA damage checkpoint kinase Ataxia Telangiectasia Mutated (ATM) is activated by oxidative stress, ATM phosphorylation was induced in the livers of wild type mice following high fat diet feeding. We therefore examined the effects of high fat diet feeding in Atm-deficient mice. The prevalence of apoptosis and expression of the pro-apoptotic factor PUMA were significantly reduced in Atm-deficient mice fed the high fat diet when compared with wild type controls. Furthermore, high fat diet fed Atm−/− mice had significantly less hepatic fibrosis than Atm+/+ or Atm+/− mice fed the same diet. Together, these data demonstrate a prominent role for the ATM pathway in the response to hepatic fat accumulation and link ATM activation to fatty liver-induced steatoapoptosis and fibrosis, key features of NAFLD progression. PMID:22544329

  17. Targeting lactate metabolism for cancer therapeutics.

    PubMed

    Doherty, Joanne R; Cleveland, John L

    2013-09-01

    Lactate, once considered a waste product of glycolysis, has emerged as a critical regulator of cancer development, maintenance, and metastasis. Indeed, tumor lactate levels correlate with increased metastasis, tumor recurrence, and poor outcome. Lactate mediates cancer cell intrinsic effects on metabolism and has additional non-tumor cell autonomous effects that drive tumorigenesis. Tumor cells can metabolize lactate as an energy source and shuttle lactate to neighboring cancer cells, adjacent stroma, and vascular endothelial cells, which induces metabolic reprogramming. Lactate also plays roles in promoting tumor inflammation and in functioning as a signaling molecule that stimulates tumor angiogenesis. Here we review the mechanisms of lactate production and transport and highlight emerging evidence indicating that targeting lactate metabolism is a promising approach for cancer therapeutics.

  18. Targeting lactate metabolism for cancer therapeutics

    PubMed Central

    Doherty, Joanne R.; Cleveland, John L.

    2013-01-01

    Lactate, once considered a waste product of glycolysis, has emerged as a critical regulator of cancer development, maintenance, and metastasis. Indeed, tumor lactate levels correlate with increased metastasis, tumor recurrence, and poor outcome. Lactate mediates cancer cell intrinsic effects on metabolism and has additional non–tumor cell autonomous effects that drive tumorigenesis. Tumor cells can metabolize lactate as an energy source and shuttle lactate to neighboring cancer cells, adjacent stroma, and vascular endothelial cells, which induces metabolic reprogramming. Lactate also plays roles in promoting tumor inflammation and in functioning as a signaling molecule that stimulates tumor angiogenesis. Here we review the mechanisms of lactate production and transport and highlight emerging evidence indicating that targeting lactate metabolism is a promising approach for cancer therapeutics. PMID:23999443

  19. Dinosaur lactation?

    PubMed

    Else, Paul L

    2013-02-01

    Lactation is a process associated with mammals, yet a number of birds feed their newly hatched young on secretions analogous to the milk of mammals. These secretions are produced from various sections (crop organ, oesophageal lining and proventriculus) of the upper digestive tract and possess similar levels of fat and protein, as well as added carotenoids, antibodies and, in the case of pigeons and doves, epidermal growth factor. Parental care in avian species has been proposed to originate from dinosaurs. This study examines the possibility that some dinosaurs used secretory feeding to increase the rate of growth of their young, estimated to be similar to that of present day birds and mammals. Dinosaur 'lactation' could also have facilitated immune responses as well as extending parental protection as a result of feeding newly hatched young in nest environments. While the arguments for dinosaur lactation are somewhat generic, a case study for lactation in herbivorous site-nesting dinosaurs is presented. It is proposes that secretory feeding could have been used to bridge the gap between hatching and establishment of the normal diet in some dinosaurs.

  20. Metabolic Syndrome: Nonalcoholic Fatty Liver Disease.

    PubMed

    Williams, Tracy

    2015-08-01

    Although nonalcoholic fatty liver disease (NAFLD) is not one of the defining criteria for metabolic syndrome, it is a common hepatic manifestation. NAFLD includes a spectrum of histologic findings ranging from simple steatosis, known as nonalcoholic fatty liver, to nonalcoholic steatohepatitis (NASH). To make the diagnosis of NAFLD, other etiologies of steatosis or hepatitis, such as hepatotoxic drugs, excessive alcohol intake, congenital errors of metabolism, or viral hepatitis, must be ruled out. After ruling out other conditions, the diagnosis of NAFLD often is made clinically, but a definitive diagnosis of NASH requires liver biopsy. As with other complications of metabolic syndrome, insulin resistance is thought to be an underlying etiology of NAFLD. Management strategies attempt to reverse or improve insulin resistance while minimizing liver damage. The strongest evidence supports lifestyle modifications with weight loss, but there is some evidence to support bariatric surgery, medical therapy with insulin-sensitizing agents, and/or pharmacotherapy to promote weight loss. Cardiovascular disease is the major cause of mortality in patients with NAFLD, so management must include modification of cardiovascular risk factors. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  1. Policy considerations for the introduction and promotion of the lactational amenorrhea method: advantages and disadvantages of LAM.

    PubMed

    Kennedy, K I; Kotelchuck, M

    1998-09-01

    Some attributes of LAM are unquestionably positive, such as the fact that it is effective. Clinical trials of LAM have upheld the Bellagio Consensus that the chance of pregnancy is less than 2% in the first 6 months postpartum in amenorrheic women who are fully or nearly fully breastfeeding. Secondary data analyses in numerous settings have drawn the same conclusion. Whether as a strategy or a method, used correctly or even if used imperfectly, LAM is a reliable way to avoid pregnancy. To the extent that LAM represents an additional contraceptive option, this is also clearly positive since a broad array of contraceptive options maximizes the likelihood of finding a good fit between user and method, and increases contraceptive use. Other characteristics of LAM represent potentially positive impacts. If LAM is shown to be an effective conduit to other modern methods, the implications are profoundly positive. If LAM is cost effective, for households and/or for programs, this will also make the method extraordinarily attractive. Conversely, some aspects of LAM are negative, such as the fact that it affords no protection against STDs, it requires counseling from a well-informed provider, and intensive breastfeeding can make heavy demands on the woman's time. Many of the remaining attributes of LAM may not be important to a policy decision about LAM promotion. For example, whether LAM is actualized as a strategy or a method may not be important to a decision to promote LAM, although it has a huge impact on how services are delivered. Some factors may be profound on a local or individual level. For example, one simple factor, such as the absence of full/nearly full breastfeeding, can rule out the method as an option, while another, such as the fact that it provides the needed waiting period during vasectomy counseling, can make LAM the method of choice. Although LAM seems unlikely to have widespread popularity in societies like the United States, within such settings are

  2. Nonalcoholic fatty liver disease.

    PubMed

    Krawczyk, Marcin; Bonfrate, Leonilde; Portincasa, Piero

    2010-10-01

    Non-alcoholic fatty liver disease (NAFLD), the most common liver disorder in the Western world, is a clinico-histopathological entity in which excessive triglyceride accumulation in the liver occurs. Non-alcoholic steatohepatitis (NASH) represents the necroinflammatory form, which can lead to advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. The pathogenesis of NAFLD/NASH is complex but increased visceral adiposity plus insulin resistance with increased free fatty acids release play an initial key role for the onset and perpetuation of liver steatosis. Further events in the liver include oxidative stress and lipid peroxidation, decreased antioxidant defences, early mitochondrial dysfunction, iron accumulation, unbalance of adipose-derived adipokines with a chronic proinflammatory status, and gut-derived microbial adducts. New gene polymorphisms increasing the risk of fatty liver, namely APOC3 and PNPLA3, have been lately identified allowing further insights into the pathogenesis of this condition. In our review pathophysiological, genetic, and essential diagnostic and therapeutic aspects of NAFLD are examined with future trends in this field highlighted. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. A maternal 'junk food' diet in pregnancy and lactation promotes an exacerbated taste for 'junk food' and a greater propensity for obesity in rat offspring.

    PubMed

    Bayol, Stéphanie A; Farrington, Samantha J; Stickland, Neil C

    2007-10-01

    Obesity is generally associated with high intake of junk foods rich in energy, fat, sugar and salt combined with a dysfunctional control of appetite and lack of exercise. There is some evidence to suggest that appetite and body mass can be influenced by maternal food intake during the fetal and suckling life of an individual. However, the influence of a maternal junk food diet during pregnancy and lactation on the feeding behaviour and weight gain of the offspring remains largely uncharacterised. In this study, six groups of rats were fed either rodent chow alone or with a junk food diet during gestation, lactation and/or post-weaning. The daily food intakes and body mass were measured in forty-two pregnant and lactating mothers as well as in 216 offspring from weaning up to 10 weeks of age. Results showed that 10 week-old rats born to mothers fed the junk food diet during gestation and lactation developed an exacerbated preference for fatty, sugary and salty foods at the expense of protein-rich foods when compared with offspring fed a balanced chow diet prior to weaning or during lactation alone. Male and female offspring exposed to the junk food diet throughout the study also exhibited increased body weight and BMI compared with all other offspring. This study shows that a maternal junk food diet during pregnancy and lactation may be an important contributing factor in the development of obesity.

  4. Nonalcoholic Fatty Liver Disease & NASH

    MedlinePlus

    ... liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Weight loss can reduce fat in the liver, inflammation, and fibrosis. No medicines have been approved to treat NAFLD and NASH. Eating, ... Clinical Trials The National Institute ...

  5. Hepatic triglyceride synthesis and nonalcoholic fatty liver disease.

    PubMed

    Choi, Steve S; Diehl, Anna Mae

    2008-06-01

    Nonalcoholic fatty liver disease is a spectrum of diseases ranging from simple steatosis to cirrhosis. The hallmark of nonalcoholic fatty liver disease is hepatocyte accumulation of triglycerides. We will review the role of triglyceride synthesis in nonalcoholic fatty liver disease progression and summarize recent findings about triglyceride synthesis inhibition and prevention of progressive disease. Attempts to inhibit triglyceride synthesis in animal models have resulted in improvement in hepatic steatosis. Studies in animal models of nonalcoholic fatty liver disease demonstrate that inhibition of acyl-coenzyme A:diacylglycerol acyltransferase, the enzyme that catalyzes the final step in triglyceride synthesis, results in improvement in hepatic steatosis and insulin sensitivity. We recently confirmed that hepatic specific inhibition of acyl-coenzyme A:diacylglycerol acyltransferase with antisense oligonucleotides improves hepatic steatosis in obese, diabetic mice but, unexpectedly, exacerbated injury and fibrosis in that model of progressive nonalcoholic fatty liver disease. When hepatocyte triglyceride synthesis was inhibited, free fatty acids accumulated in the liver, leading to induction of fatty acid oxidizing systems that increased hepatic oxidative stress and liver damage. These findings suggest that the ability to synthesize triglycerides may, in fact, be protective in obesity. Nonalcoholic fatty liver disease is strongly associated with obesity and peripheral insulin resistance. Peripheral insulin resistance increases lipolysis in adipose depots, promoting increased free fatty acid delivery to the liver. In states of energy excess, such as obesity, the latter normally triggers hepatic triglyceride synthesis. When hepatic triglyceride synthesis is unable to accommodate increased hepatocyte free fatty acid accumulation, however, lipotoxicity results. Thus, rather than being hepatotoxic, liver triglyceride accumulation is actually hepato-protective in obese

  6. The Riddle of Nonalcoholic Fatty Liver Disease: Progression From Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis

    PubMed Central

    Sharma, Mithun; Mitnala, Shasikala; Vishnubhotla, Ravi K.; Mukherjee, Rathin; Reddy, Duvvur N.; Rao, Padaki N.

    2015-01-01

    Nonalcoholic fatty liver (NAFL) is an emerging global epidemic which progresses to nonalcoholic steatohepatitis (NASH) and cirrhosis in a subset of subjects. Various reviews have focused on the etiology, epidemiology, pathogenesis and treatment of NAFLD. This review highlights specifically the triggers implicated in disease progression from NAFL to NASH. The integrating role of genes, dietary factors, innate immunity, cytokines and gut microbiome have been discussed. PMID:26155043

  7. The Riddle of Nonalcoholic Fatty Liver Disease: Progression From Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis.

    PubMed

    Sharma, Mithun; Mitnala, Shasikala; Vishnubhotla, Ravi K; Mukherjee, Rathin; Reddy, Duvvur N; Rao, Padaki N

    2015-06-01

    Nonalcoholic fatty liver (NAFL) is an emerging global epidemic which progresses to nonalcoholic steatohepatitis (NASH) and cirrhosis in a subset of subjects. Various reviews have focused on the etiology, epidemiology, pathogenesis and treatment of NAFLD. This review highlights specifically the triggers implicated in disease progression from NAFL to NASH. The integrating role of genes, dietary factors, innate immunity, cytokines and gut microbiome have been discussed.

  8. Induced lactation: gaining a better understanding.

    PubMed

    Wittig, Sarah L; Spatz, Diane L

    2008-01-01

    Although a small minority in the United States, a number of adoptive mothers continue to seek information regarding the induction of lactation. Because of the level of support needed by these women to successfully induce lactation, it is necessary for nurses and other healthcare workers to gain a thorough understanding of the various processes and medications frequently used. Often, women who induce lactation cannot produce enough milk to exclusively breastfeed their infant but find satisfaction in this rigorous process because of the maternal-infant bonding it promotes. The adoptive mother seeking to induce lactation is a unique client in need of highly tailored and personalized care.

  9. A maternal cafeteria diet during gestation and lactation promotes adiposity and impairs skeletal muscle development and metabolism in rat offspring at weaning.

    PubMed

    Bayol, Stéphanie A; Simbi, Bigboy H; Stickland, Neil C

    2005-09-15

    We examined the effects of a maternal cafeteria diet on skeletal muscle and adipose tissue development in the offspring at weaning. Rats born to mothers fed the cafeteria diet either during gestation alone or during both gestation and lactation exhibited a 25% reduction in muscle cross-sectional area with approximately 20% fewer fibres compared with pups fed a balanced chow diet. Maintaining the cafeteria diet during lactation increased intramuscular lipid content and fat pad weights characterized by adipocyte hypertrophy but not hyperplasia. These pups also had elevated muscle IGF-1, IGF-1 receptor, and PPARgamma mRNA levels, which may indicate an attempt to maintain normal insulin sensitivity. The increased adiposity and elevated IGF-1, IGF-1 receptor and PPARgamma mRNAs were not seen in the pups rehabilitated to the balanced diet during lactation. However, these pups exhibited reduced muscle cell proliferation (PCNA) with reduced insulin receptor and a trend towards reduced glucose transporter (GLUT)-4 mRNAs when compared with pups fed a balanced chow diet, indicating possible alterations in glucose uptake by muscle tissue. Therefore, rats born to mothers fed a cafeteria diet during gestation alone or during both gestation and lactation exhibited impaired skeletal muscle development and metabolic disorders normally associated with insulin resistance as early as the weaning stage.

  10. Maternal obesity programs offspring non-alcoholic fatty liver disease through disruption of 24-h rhythms in mice.

    PubMed

    Mouralidarane, A; Soeda, J; Sugden, D; Bocianowska, A; Carter, R; Ray, S; Saraswati, R; Cordero, P; Novelli, M; Fusai, G; Vinciguerra, M; Poston, L; Taylor, P D; Oben, J A

    2015-09-01

    Maternal obesity increases offspring propensity to metabolic dysfunctions and to non-alcoholic fatty liver disease (NAFLD), which may lead to cirrhosis or liver cancer. The circadian clock is a transcriptional/epigenetic molecular machinery synchronising physiological processes to coordinate energy utilisation within a 24-h light/dark period. Alterations in rhythmicity have profound effects on metabolic pathways, which we sought to investigate in offspring with programmed NAFLD. Mice were fed a standard or an obesogenic diet (OD), before and throughout pregnancy, and during lactation. Offspring were weaned onto standard or an OD at 3 weeks postpartum and housed in 12:12 light/dark conditions. Biochemical and histological indicators of NAFLD and fibrosis, analysis of canonical clock genes with methylation status and locomotor activity were investigated at 6 months. We show that maternal obesity interacts with an obesogenic post-weaning diet to promote the development of NAFLD with disruption of canonical metabolic rhythmicity gene expression in the liver. We demonstrate hypermethylation of BMAL-1 (brain and muscle Arnt like-1) and Per2 promoter regions and altered 24-h rhythmicity of hepatic pro-inflammatory and fibrogenic mediators. These data implicate disordered circadian rhythms in NAFLD and suggest that disruption of this system during critical developmental periods may be responsible for the onset of chronic liver disease in adulthood.

  11. A metabolic core model elucidates how enhanced utilization of glucose and glutamine, with enhanced glutamine-dependent lactate production, promotes cancer cell growth: The WarburQ effect.

    PubMed

    Damiani, Chiara; Colombo, Riccardo; Gaglio, Daniela; Mastroianni, Fabrizia; Pescini, Dario; Westerhoff, Hans Victor; Mauri, Giancarlo; Vanoni, Marco; Alberghina, Lilia

    2017-09-01

    Cancer cells share several metabolic traits, including aerobic production of lactate from glucose (Warburg effect), extensive glutamine utilization and impaired mitochondrial electron flow. It is still unclear how these metabolic rearrangements, which may involve different molecular events in different cells, contribute to a selective advantage for cancer cell proliferation. To ascertain which metabolic pathways are used to convert glucose and glutamine to balanced energy and biomass production, we performed systematic constraint-based simulations of a model of human central metabolism. Sampling of the feasible flux space allowed us to obtain a large number of randomly mutated cells simulated at different glutamine and glucose uptake rates. We observed that, in the limited subset of proliferating cells, most displayed fermentation of glucose to lactate in the presence of oxygen. At high utilization rates of glutamine, oxidative utilization of glucose was decreased, while the production of lactate from glutamine was enhanced. This emergent phenotype was observed only when the available carbon exceeded the amount that could be fully oxidized by the available oxygen. Under the latter conditions, standard Flux Balance Analysis indicated that: this metabolic pattern is optimal to maximize biomass and ATP production; it requires the activity of a branched TCA cycle, in which glutamine-dependent reductive carboxylation cooperates to the production of lipids and proteins; it is sustained by a variety of redox-controlled metabolic reactions. In a K-ras transformed cell line we experimentally assessed glutamine-induced metabolic changes. We validated computational results through an extension of Flux Balance Analysis that allows prediction of metabolite variations. Taken together these findings offer new understanding of the logic of the metabolic reprogramming that underlies cancer cell growth.

  12. Lactate dehydrogenase test

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003471.htm Lactate dehydrogenase test To use the sharing features on this page, please enable JavaScript. Lactate dehydrogenase (LDH) is a protein that helps produce energy ...

  13. Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis.

    PubMed

    Koo, Seung-Hoi

    2013-09-01

    Liver plays a central role in the biogenesis of major metabolites including glucose, fatty acids, and cholesterol. Increased incidence of obesity in the modern society promotes insulin resistance in the peripheral tissues in humans, and could cause severe metabolic disorders by inducing accumulation of lipid in the liver, resulting in the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD, which is characterized by increased fat depots in the liver, could precede more severe diseases such as non-alcoholic steatohepatitis (NASH), cirrhosis, and in some cases hepatocellular carcinoma. Accumulation of lipid in the liver can be traced by increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, or the increased incidence of de novo lipogenesis. In this review, I would like to focus on the roles of individual pathways that contribute to the hepatic steatosis as a precursor for the NAFLD.

  14. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    PubMed Central

    Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH give crucial information, not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents. An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH. Animal models of NAFLD/NASH are divided into genetic, dietary, and combination models. In this paper, we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages. PMID:22654421

  15. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    PubMed

    Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio

    2012-05-21

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH give crucial information, not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents. An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH. Animal models of NAFLD/NASH are divided into genetic, dietary, and combination models. In this paper, we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.

  16. Probiotics in Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, and Cirrhosis.

    PubMed

    Qamar, Amir A

    2015-01-01

    With the growing epidemic of obesity, the incidence of both nonalcoholic fatty liver disease (NAFL) and nonalcoholic steatohepatitis (NASH) is increasing. The intestinal microbiota differs between individuals who are obese or have normal body mass indices. Animal studies have shown increased intestinal permeability in NAFL, NASH, and cirrhosis. This increases the risk of oxidative and inflammatory injury to the liver from intestinal microbacteria. It may also increase the risk of fatty acid injury and fatty deposition. Bacterial translocation is associated with increased portal hypertension and hepatic encephalopathy in cirrhosis. By preventing bacterial adhesion and translocation, probiotics may have a role in the management of patients with NAFL, NASH, and cirrhosis. Multiple small studies have suggested that probiotics improve some of the clinical markers of activity in patients with NAFL and NASH. Controlled studies have also shown improved outcomes in patients with cirrhosis who were treated with probiotics.

  17. [Pediatric nonalcoholic fatty liver disease/nonalcoholic steatohepatitis].

    PubMed

    Takahashi, Yoshihisa; Fukusato, Toshio; Inui, Ayano; Fujisawa, Tomoo

    2012-10-01

    Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is a hepatic disease associated with metabolic syndrome. In recent years, pediatric NAFLD has increased in line with the increased prevalence of pediatric obesity. The estimated prevalence of pediatric NAFLD is 2.6-9.6%. With regard to the pathogenesis of NAFLD/ NASH, the "two-hit" or "multiple-hit" hypothesis is widely accepted, and many genetic and environmental factors are associated with the development of NAFLD/NASH. Liver biopsy is regarded as the gold standard for the diagnosis of NAFLD/NASH. Pediatric NAFLD has different histopathological characteristics from those of adult NAFLD. Although pharmacotherapy has been studied in clinical trials, lifestyle modification by diet and exercise remains the mainstay of treatment for NAFLD/NASH.

  18. Nonalcoholic fatty liver disease: a systematic review.

    PubMed

    Rinella, Mary E

    2015-06-09

    Nonalcoholic fatty liver disease and its subtype nonalcoholic steatohepatitis affect approximately 30% and 5%, respectively, of the US population. In patients with nonalcoholic steatohepatitis, half of deaths are due to cardiovascular disease and malignancy, yet awareness of this remains low. Cirrhosis, the third leading cause of death in patients with nonalcoholic fatty liver disease, is predicted to become the most common indication for liver transplantation. To illustrate how to identify patients with nonalcoholic fatty liver disease at greatest risk of nonalcoholic steatohepatitis and cirrhosis; to discuss the role and limitations of current diagnostics and liver biopsy to diagnose nonalcoholic steatohepatitis; and to provide an outline for the management of patients across the spectrum of nonalcoholic fatty liver disease. PubMed was queried for published articles through February 28, 2015, using the search terms NAFLD and cirrhosis, mortality, biomarkers, and treatment. A total of 88 references were selected, including 16 randomized clinical trials, 44 cohort or case-control studies, 6 population-based studies, and 7 meta-analyses. Sixty-six percent of patients older than 50 years with diabetes or obesity are thought to have nonalcoholic steatohepatitis with advanced fibrosis. Even though the ability to identify the nonalcoholic steatohepatitis subtype within those with nonalcoholic fatty liver disease still requires liver biopsy, biomarkers to detect advanced fibrosis are increasingly reliable. Lifestyle modification is the foundation of treatment for patients with nonalcoholic steatosis. Available treatments with proven benefit include vitamin E, pioglitazone, and obeticholic acid; however, the effect size is modest (<50%) and none is approved by the US Food and Drug Administration. The association between nonalcoholic steatohepatitis and cardiovascular disease is clear, though causality remains to be proven in well-controlled prospective studies. The

  19. Imaging Pregnant and Lactating Patients.

    PubMed

    Tirada, Nikki; Dreizin, David; Khati, Nadia J; Akin, Esma A; Zeman, Robert K

    2015-10-01

    As use of imaging in the evaluation of pregnant and lactating patients continues to increase, misperceptions of radiation and safety risks have proliferated, which has led to often unwarranted concerns among patients and clinicians. When radiologic examinations are appropriately used, the benefits derived from the information gained usually outweigh the risks. This review describes appropriateness and safety issues, estimated doses for imaging examinations that use iodizing radiation (ie, radiography, computed tomography, nuclear scintigraphy, and fluoroscopically guided interventional radiology), radiation risks to the mother and conceptus during various stages of pregnancy, and use of iodinated or gadolinium-based contrast agents and radiotracers in pregnant and lactating women. Maternal radiation risk must be weighed with the potential consequences of missing a life-threatening diagnosis such as pulmonary embolus. Fetal risks (ie, spontaneous abortion, teratogenesis, or carcinogenesis) vary with gestational age and imaging modality and should be considered in the context of the potential benefit of medically necessary diagnostic imaging. When feasible and medically indicated, modalities that do not use ionizing radiation (eg, magnetic resonance imaging) are preferred in pregnant and lactating patients. Radiologists should strive to minimize risks of radiation to the mother and fetus, counsel patients effectively, and promote a realistic understanding of risks related to imaging during pregnancy and lactation.

  20. Glitazones for human nonalcoholic steatohepatitis

    PubMed Central

    Pais, Raluca; Moraru, Ioana; Ratziu, Vlad

    2011-01-01

    The rationale for specific pharmacologic therapy in nonalcoholic steatohepatitis (NASH) is determined by the potential for disease progression and the difficulties, in many patients, of successfully implementing diet and lifestyle changes over the long term. Owing to their ability to correct insulin resistance, insulin-sensitizing agents are attractive candidates for the treatment of NASH. In this review we provide an insight into the mechanism of action, therapeutic efficacy and safety issues regarding the use of glitazones in NASH. PMID:21922031

  1. Lactation and reproduction*

    PubMed Central

    Thomson, A. M.; Hytten, F. E.; Black, A. E.

    1975-01-01

    The authors review the literature on the effect of lactation on fertility in the absence of contraception and on the effects of contraceptive measures on lactation. They examine data from several countries on the intervals between births and on the return of menstruation and ovulation after childbirth, comparing lactating with nonlactating women. They conclude that lactation is an inefficient contraceptive for the individual, but that in populations sustained lactation is associated with reduced fertility. Possible physiological mechanisms causing lactation amenorrhoea are discussed. Though much of the literature on the effect of contraceptives on lactation is inadequate, there is general agreement that the estrogen component of hormonal preparations has an adverse effect on lactation, but that progestins alone do not. Many questions remain. Is this effect seen in established lactation, or only in the puerperal period? Is it a direct pharmacological effect, or are pill-users the mothers least motivated to maintain breast-feeding? Does a close relationship exist between hormones given and lactation performance? The authors comment on some of the technical deficiencies of previous studies in this field and discuss practical possibilities of, and limitations to, obtaining adequate scientific information in the future. PMID:1084804

  2. CKD and nonalcoholic fatty liver disease.

    PubMed

    Targher, Giovanni; Chonchol, Michel B; Byrne, Christopher D

    2014-10-01

    The possible link between nonalcoholic fatty liver disease and chronic kidney disease (CKD) recently has attracted considerable scientific interest. Accumulating clinical evidence indicates that the presence and severity of nonalcoholic fatty liver disease is associated significantly with CKD (defined as decreased estimated glomerular filtration rate and/or proteinuria) and that nonalcoholic fatty liver disease predicts the development and progression of CKD, independently of traditional cardiorenal risk factors. Experimental evidence also suggests that nonalcoholic fatty liver disease itself may exacerbate systemic and hepatic insulin resistance, cause atherogenic dyslipidemia, and release a variety of proinflammatory, procoagulant, pro-oxidant, and profibrogenic mediators that play important roles in the development and progression of CKD. However, despite the growing evidence linking nonalcoholic fatty liver disease with CKD, it has not been definitively established whether a causal association exists. The clinical implication for these findings is that patients with nonalcoholic fatty liver disease may benefit from more intensive surveillance or early treatment interventions to decrease the risk of CKD. In this review, we discuss the evidence linking nonalcoholic fatty liver disease with CKD and the putative mechanisms by which nonalcoholic fatty liver disease contributes to kidney damage. We also briefly discuss current treatment options for this increasingly prevalent disease that is likely to have an important future impact on the global burden of disease.

  3. Surfactant-promoted Prussian Blue-modified carbon electrodes: enhancement of electro-deposition step, stabilization, electrochemical properties and application to lactate microbiosensors for the neurosciences.

    PubMed

    Salazar, P; Martín, M; O'Neill, R D; Roche, R; González-Mora, J L

    2012-04-01

    We report here for the first time a comparison of the beneficial effects of different cationic surfactants - cetyl trimethyl ammonium bromide (CTAB), benzethonium chloride (BZT) and cetylpyridinium chloride (CPC) - for the electrochemical synthesis of Prussian Blue (PB) films, using cyclic voltammetry (CV), on screen-printed carbon electrodes (SPCEs). Their electrochemical properties were investigated, paying special attention to parameters such as the amount of PB deposited, film thickness, charge transfer rate, permeability, reversibility, stability and sensitivity to hydrogen peroxide detection. All surfactant-enhanced PB-modified SPCEs displayed a significant improvement in their electrochemical properties compared with PB-modified SPCEs formed in the absence of surfactants. Surfactant-modified electrodes displayed a consistently higher PB surface concentration value of 2.1±0.4×10(-8) mol cm(-2) (mean±SD, n=3) indicating that PB deposition efficiency was improved 2-3 fold. K(+) and Na(+) permeability properties of the films were also studied, as were kinetic parameters, such as the surface electron transfer rate constant (k(s)) and the transfer coefficient (α). The hydrogen peroxide sensitivity of surfactant-modified PB films generated by 10 electro-deposition CV cycles gave values of 0.63 A M(-1) cm(-2), which is higher than those reported previously for SPCEs by other authors. Finally, the first lactate microbiosensor described in the literature based on BZT-modified PB-coated carbon fiber electrodes is presented. Its very small cross-section (~10 μm diameter) makes it particularly suitable for neuroscience studies in vivo.

  4. Promotion

    PubMed Central

    Alam, Hasan B.

    2013-01-01

    This article gives an overview of the promotion process in an academic medical center. A description of different promotional tracks, tenure and endowed chairs, and the process of submitting an application is provided. Finally, some practical advice about developing skills and attributes that can help with academic growth and promotion is dispensed. PMID:24436683

  5. Introduction of the human growth hormone gene into the guinea pig mammary gland by in vivo transfection promotes sustained expression of human growth hormone in the milk throughout lactation.

    PubMed

    Hens, J R; Amstutz, M D; Schanbacher, F L; Mather, I H

    2000-10-18

    We tested the feasibility of transfecting mammary tissue in vivo with an expression plasmid encoding the human growth hormone (hGH) gene, under the control of the cytomegalovirus promoter. Guinea pig mammary glands were transfected with plasmid DNA infused through the nipple canal and expression was monitored in control and transfected glands by radioimmunoassay of milk samples for hGH. Sustained expression of hGH throughout lactation was attained with a polyion transfection complex shown to be optimal for the transfection of bovine mammary cells, in vitro. However, contrary to expectations, hGH expression was consistently 5- to 10-fold higher when DEAE-dextran was used alone for transfection. Thus polyion complexes which are optimal for the transfection of cells in vitro may not be optimal in vivo. The highest concentrations of hGH in milk were obtained when glands were transfected within 3 days before parturition. This method may have application for studying the biological role or physical properties of recombinant proteins expressed in low quantities, or for investigating the regulation of gene promoters without the need to construct viral vectors or produce transgenic animals.

  6. Histopathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    PubMed Central

    Takahashi, Yoshihisa; Fukusato, Toshio

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome, is the most common chronic liver disease, and the prevalence is rapidly increasing worldwide. Nonalcoholic steatohepatitis (NASH), the severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Although noninvasive clinical scores and image-based diagnosis for NAFLD have improved, histopathological evaluation of biopsy specimens remains the gold standard for diagnosing NAFLD/NASH. Steatosis, lobular inflammation, and hepatocellular ballooning are all necessary components for the diagnosis of NASH; fibrosis is also typically observed. Other histopathological abnormalities commonly observed in NASH include hepatocellular glycogenated nuclei, lipogranulomas, and acidophil bodies. The characteristics of pediatric NAFLD/NASH differ from adult NAFLD/NASH. Specifically, steatosis and portal inflammation are more severe in pediatric NAFLD, while intralobular inflammation and perisinusoidal fibrosis are milder. Although interobserver agreement for evaluating the extent of steatosis and fibrosis is high, agreement is low for intralobular and portal inflammation. A recently reported histological variant of HCC, steatohepatitic HCC (SH-HCC), shows features that resemble non-neoplastic steatohepatitis, and is thought to be strongly associated with underlying NASH. In this report, we review the histopathological features of NAFLD/NASH. PMID:25400438

  7. Histopathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    PubMed

    Takahashi, Yoshihisa; Fukusato, Toshio

    2014-11-14

    Nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome, is the most common chronic liver disease, and the prevalence is rapidly increasing worldwide. Nonalcoholic steatohepatitis (NASH), the severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Although noninvasive clinical scores and image-based diagnosis for NAFLD have improved, histopathological evaluation of biopsy specimens remains the gold standard for diagnosing NAFLD/NASH. Steatosis, lobular inflammation, and hepatocellular ballooning are all necessary components for the diagnosis of NASH; fibrosis is also typically observed. Other histopathological abnormalities commonly observed in NASH include hepatocellular glycogenated nuclei, lipogranulomas, and acidophil bodies. The characteristics of pediatric NAFLD/NASH differ from adult NAFLD/NASH. Specifically, steatosis and portal inflammation are more severe in pediatric NAFLD, while intralobular inflammation and perisinusoidal fibrosis are milder. Although interobserver agreement for evaluating the extent of steatosis and fibrosis is high, agreement is low for intralobular and portal inflammation. A recently reported histological variant of HCC, steatohepatitic HCC (SH-HCC), shows features that resemble non-neoplastic steatohepatitis, and is thought to be strongly associated with underlying NASH. In this report, we review the histopathological features of NAFLD/NASH.

  8. Rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    PubMed

    Imajo, Kento; Yoneda, Masato; Kessoku, Takaomi; Ogawa, Yuji; Maeda, Shin; Sumida, Yoshio; Hyogo, Hideyuki; Eguchi, Yuichiro; Wada, Koichiro; Nakajima, Atsushi

    2013-11-04

    Research in nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), has been limited by the availability of suitable models for this disease. A number of rodent models have been described in which the relevant liver pathology develops in an appropriate metabolic context. These models are promising tools for researchers investigating one of the key issues of NASH: not so much why steatosis occurs, but what causes the transition from simple steatosis to the inflammatory, progressive fibrosing condition of steatohepatitis. The different rodent models can be classified into two large groups. The first includes models in which the disease is acquired after dietary or pharmacological manipulation, and the second, genetically modified models in which liver disease develops spontaneously. To date, no single rodent model has encompassed the full spectrum of human disease progression, but individual models can imitate particular characteristics of human disease. Therefore, it is important that researchers choose the appropriate rodent models. The purpose of the present review is to discuss the metabolic abnormalities present in the currently available rodent models of NAFLD, summarizing the strengths and weaknesses of the established models and the key findings that have furthered our understanding of the disease's pathogenesis.

  9. Phosphatase-like activity, DNA binding, DNA hydrolysis, anticancer and lactate dehydrogenase inhibition activity promoting by a new bis-phenanthroline dicopper(II) complex.

    PubMed

    Anbu, Sellamuthu; Kandaswamy, Muthusamy; Kamalraj, Subban; Muthumarry, Johnpaul; Varghese, Babu

    2011-07-28

    A new bis-phenanthroline dicopper(II) complex has been synthesized and characterized by elemental analysis and spectroscopic methods. The molecular structure of the dinuclear Cu(II) complex [Cu(2)(μ-CH(3)COO)(μ-H(2)O)(μ-OH)(phen)(2)](2+) (phen = 1,10-phenanthroline) (1) was determined by single crystal X-ray diffraction technique. The coordination environment around each Cu(II) ion in complex 1 can be described as slightly distorted square pyramidal geometry. The distance between the CuCu centers in the complex is found to be 2.987 Å. The electronic, redox, phosphate hydrolysis, DNA binding and DNA cleavage have been studied. The antiproliferative effect of complex 1 was confirmed by the lactate dehydrogenase (LDH) enzyme level in MCF-7 cancer cell lysate and content media. The dicopper(II) complex inhibited the LDH enzyme as well as the growth of the human breast cancer MCF7 cell line at an IC(50) value of 0.011 μg ml(-1). The results strongly suggest that complex 1 is a good cancer therapeutic agent. Electrochemical studies of complex 1 showed an irreversible, followed by a quasi-reversible, one electron reduction processes between -0.20 to -0.8 V. Michaelis-Menten kinetic parameters for the hydrolysis of 4-nitrophenyl phosphate by complex 1 are k(cat) = 3.56 × 10(-2) s(-1) and K(M) = 4.3 × 10(-2) M. Complex 1 shows good binding propensity to calf thymus DNA, with a binding constant value of 1.3 (±0.13) × 10(5) M(-1) (s = 2.1). The size of the binding site and viscosity data suggest a DNA intercalative binding nature of the complex. Complex 1 shows efficient hydrolytic cleavage of supercoiled pBR322-DNA in the dark and in the absence of any external reagents, as demonstrated by the T4 ligase experiment. The pseudo-Michaelis-Menten kinetic parameters for DNA hydrolysis by complex 1 are k(cat) = 1.27 ± 0.4 h(-1) and K(M) = 7.7 × 10(-2) M.

  10. Physiology of lactation

    USDA-ARS?s Scientific Manuscript database

    The breast changes in size, shape, and function during puberty, pregnancy, and lactation. The physiology of lactation is reviewed here. The breast is composed of fat and connective tissue that supports a tubuloalveolar structure. During development, anatomic changes involving new lobule formation an...

  11. Progression of non-alcoholic steatosis to steatohepatitis and fibrosis parallels cumulative accumulation of danger signals that promote inflammation and liver tumors in a high fat-cholesterol-sugar diet model in mice.

    PubMed

    Ganz, Michal; Bukong, Terence N; Csak, Timea; Saha, Banishree; Park, Jin-Kyu; Ambade, Aditya; Kodys, Karen; Szabo, Gyongyi

    2015-06-16

    Non-alcoholic fatty liver disease (NAFLD) is becoming a pandemic. While multiple 'hits' have been reported to contribute to NAFLD progression to non-alcoholic steatohepatitis (NASH), fibrosis and liver cancer, understanding the natural history of the specific molecular signals leading to hepatocyte damage, inflammation and fibrosis, is hampered by the lack of suitable animal models that reproduce disease progression in humans. The purpose of this study was first, to develop a mouse model that closely mimics progressive NAFLD covering the spectrum of immune, metabolic and histopathologic abnormalities present in human disease; and second, to characterize the temporal relationship between sterile/exogenous danger signals, inflammation, inflammasome activation and NAFLD progression. Male C57Bl/6 mice were fed a high fat diet with high cholesterol and a high sugar supplement (HF-HC-HSD) for 8, 27, and 49 weeks and the extent of steatosis, liver inflammation, fibrosis and tumor development were evaluated at each time point. The HF-HC-HSD resulted in liver steatosis at 8 weeks, progressing to steatohepatitis and early fibrosis at 27 weeks, and steatohepatitis, fibrosis, and tumor development at 49 weeks compared to chow diet. Steatohepatitis was characterized by increased levels of MCP-1, TNFα, IL-1β and increased liver NASH histological score. We found increased serum levels of sterile danger signals, uric acid and HMGB1, as early as 8 weeks, while endotoxin and ATP levels increased only after 49 weeks. Increased levels of these sterile and microbial danger signals paralleled upregulation and activation of the multiprotein complex inflammasome. At 27, 49 weeks of HF-HC-HSD, activation of M1 macrophages and loss of M2 macrophages as well as liver fibrosis were present. Finally, similar to human NASH, liver tumors occurred in 41% of mice in the absence of cirrhosis and livers expressed increased p53 and detectable AFP. HF-HC-HSD over 49 weeks induces the full spectrum

  12. The Differentiation of Intestinal-Failure-Associated Liver Disease from Nonalcoholic Fatty Liver and Nonalcoholic Steatohepatitis.

    PubMed

    Buchman, Alan L; Naini, Bita V; Spilker, Bert

    2017-02-01

    Intestinal failure-associated liver disease (IFALD), formerly known as parenteral nutrition-associated liver disease has often been listed in textbooks as an example of nonalcoholic fatty liver disease (NAFLD). However, the etiology, pathophysiology, epidemiology, histology, and progression differ substantially between the conditions defined as NAFLD and the disease, IFALD. Therefore, IFALD should not be defined or considered as a type or a cause of nonalcoholic fatty liver or nonalcoholic steatohepatitis, but rather as a distinct disease.

  13. Pediatric Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Delvin, Edgard; Patey, Natasha; Dubois, Josée; Henderson, Melanie; Lévy, Émile

    2015-01-01

    Summary The rapidly increasing prevalence of childhood obesity and its associated co-morbidities such as hypertriglyceridemia, hyper-insulinemia, hypertension, early atherosclerosis, metabolic syndrome, and non-alcoholic fatty liver disease are major public health concerns in many countries. Therefore the trends in child and adolescent obesity should be closely monitored over time, as in the near future, we may anticipate a major increase of young adults with the stigmata of the metabolic syndrome, and of the related non-alcoholic fatty liver disease (NAFLD), that may lead to non-alcoholic steatohepatitis. PMID:28356817

  14. Pediatric nonalcoholic fatty liver disease.

    PubMed

    Bozic, Molly A; Subbarao, Girish; Molleston, Jean P

    2013-08-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the pediatric population. Increased recognition of this form of liver disease parallels the dramatic rise in childhood and adolescent obesity over the past 2 decades. Like adults, most children with NAFLD are obese, and comorbidities include insulin resistance, hypertension, and dyslipidemia. Unfortunately, pediatric NAFLD is not always a benign condition, with some children progressing to hepatic fibrosis and even cirrhosis in severe cases. The etiology of nonalcoholic steatohepatitis is not yet fully understood; however, hepatic steatosis in the context of insulin resistance and increased oxidative stress may lead to progressive disease. Although physical examination, laboratory evaluation, and radiographic findings provide clues to the potential presence of fatty liver disease, liver biopsy remains the gold standard for diagnosis. Lifestyle modification, including slow and steady weight loss, improved dietary habits, and increased daily, aerobic physical activity, remains the first-line approach in treating pediatric fatty liver disease. Antioxidant pharmacologic therapy such as use of vitamin E has shown some benefit in patients with biopsy-proven steatohepatitis. Nutrition plays an essential role not only in the development of fatty liver disease but also potentially in the treatment and prevention of progression to more severe disease.

  15. Hepatocellular carcinoma and non-alcoholic steatohepatitis: The state of play

    PubMed Central

    Charrez, Bérénice; Qiao, Liang; Hebbard, Lionel

    2016-01-01

    Hepatocellular carcinoma (HCC) is now the fifth cancer of greatest frequency and the second leading cause of cancer related deaths worldwide. Chief amongst the risks of HCC are hepatitis B and C infection, aflatoxin B1 ingestion, alcoholism and obesity. The latter can promote non-alcoholic fatty liver disease (NAFLD), that can lead to the inflammatory form non-alcoholic steatohepatitis (NASH), and can in turn promote HCC. The mechanisms by which NASH promotes HCC are only beginning to be characterized. Here in this review, we give a summary of the recent findings that describe and associate NAFLD and NASH with the subsequent HCC progression. We will focus our discussion on clinical and genomic associations that describe new risks for NAFLD and NASH promoted HCC. In addition, we will consider novel murine models that clarify some of the mechanisms that drive NASH HCC formation. PMID:26937137

  16. Advances in Pediatric Nonalcoholic Fatty Liver Disease

    PubMed Central

    Loomba, Rohit; Sirlin, Claude B.; Schwimmer, Jeffrey B.; Lavine, Joel E.

    2009-01-01

    Nonalcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease in children and adolescents in the United States. A two- to three-fold rise in the rates of obesity and overweight in children over the last 2 decades is probably responsible for the epidemic of NAFLD. Emerging data suggest that children with NASH progress to cirrhosis which may ultimately increase liver-related mortality. More worrisome is the recognition that cardiovascular risk and morbidity in children and adolescents is associated with fatty liver. Pediatric fatty liver disease often displays a histologic pattern distinct from that found in adults. Liver biopsy remains the gold standard for diagnosis of NASH. Non-invasive biomarkers are needed to identify individuals with progressive liver injury. Targeted therapies to improve liver histology and metabolic abnormalities associated with fatty liver are needed. Currently, randomized-controlled trials are underway in the pediatric population to define pharmacologic therapy for NAFLD. Public health awareness and intervention are needed to promote healthy diet, exercise, and lifestyle modifications to prevent and reduce the burden of disease in the community. PMID:19637286

  17. Metabolic regulation by lactate.

    PubMed

    Sola-Penna, Mauro

    2008-09-01

    For more than a century, the metabolic role of lactate has intrigued physiologists and biochemists. Yet, for the first half of the last century lactate had been designated as a waste product, and assigned no additional significance besides its controversial role in muscle fatigue. The decline of the lactate hypothesis for the onset of muscle fatigue and the defining of some modulatory properties attributed to lactate have increased the interest on this molecule. The present critical review aimed at evaluating some recent publications concerned with unveiling the regulatory actions of lactate in cellular function. Lactate has been described to modulate enzymes catalytic properties to affect hormonal release and responsiveness, and to control body homeostasis. Moreover, these properties are directly related to the genesis and the sustainability of pathological conditions, such as diabetes and cancer. In the end, we concluded that lactate should not be regarded as simply an anaerobic metabolite, but should be considered as a regulatory molecule that modulates the integration of metabolism.

  18. Red cell distribution width and nonalcoholic steatohepatitis

    PubMed Central

    Gulcan Kurt, Yasemin; Cayci, Tuncer; Aydin, Fevzi Nuri; Agilli, Mehmet

    2014-01-01

    Red cell distribution width is a measure of deviation of the volume of red blood cells. It is a marker of anisocytosis and often used to evaluate the possible causes of anemia. Elevated red cell distribution width levels are also associated with acute and chronic inflammatory responses. In nonalcoholic steatohepatitis, inflammation is accompanied with steatosis. For assuming red cell distribution width as a marker of nonalcoholic steatohepatitis, intervening factors such as levels of inflammatory markers should also be evaluated. PMID:25473202

  19. Nonalcoholic fatty liver disease: diagnosis and management.

    PubMed

    Wilkins, Thad; Tadkod, Altaf; Hepburn, Iryna; Schade, Robert R

    2013-07-01

    Nonalcoholic fatty liver disease is characterized by excessive fat accumulation in the liver (hepatic steatosis). Nonalcoholic steatohepatitis is characterized by steatosis, liver cell injury, and inflammation. The mechanism of nonalcoholic fatty liver disease is unknown but involves the development of insulin resistance, steatosis, inflammatory cytokines, and oxidative stress. Nonalcoholic fatty liver disease is associated with physical inactivity, obesity, and metabolic syndrome. Screening is not recommended in the general population. The diagnosis is usually made after an incidental discovery of unexplained elevation of liver enzyme levels or when steatosis is noted on imaging (e.g., ultrasonography). Patients are often asymptomatic and the physical examination is often unremarkable. No single laboratory test is diagnostic, but tests of liver function, tests for metabolic syndrome, and tests to exclude other causes of abnormal liver enzyme levels are routinely performed. Imaging studies, such as ultrasonography, computed tomography, and magnetic resonance imaging, can assess hepatic fat, measure liver and spleen size, and exclude other diseases. Liver biopsy remains the criterion standard for the diagnosis of nonalcoholic steatohepatitis. Noninvasive tests are available and may reduce the need for liver biopsy. A healthy diet, weight loss, and exercise are first-line therapeutic measures to reduce insulin resistance. There is insufficient evidence to support bariatric surgery, metformin, thiazolidinediones, bile acids, or antioxidant supplements for the treatment of nonalcoholic fatty liver disease. The long-term prognosis is not associated with an increased risk of all-cause mortality, cardiovascular disease, cancer, or liver disease.

  20. Genetics Home Reference: non-alcoholic fatty liver disease

    MedlinePlus

    ... Genetics Home Health Conditions NAFLD non-alcoholic fatty liver disease Enable Javascript to view the expand/collapse ... Open All Close All Description Non-alcoholic fatty liver disease ( NAFLD ) is a buildup of excessive fat ...

  1. Identification of master genes involved in liver key functions through transcriptomics and epigenomics of methyl donor deficiency in rat: relevance to nonalcoholic liver disease.

    PubMed

    Chen, Gaili; Broséus, Julien; Hergalant, Sébastien; Donnart, Audrey; Chevalier, Catherine; Bolaños-Jiménez, Francisco; Guéant, Jean-Louis; Houlgatte, Rémi

    2015-02-01

    Our study aims to investigate molecular events associated to methyl donor deficiency (MDD) by analyzing the transcriptome and the methylome of MDD rats in liver. Twenty-one-day-old rats born to mothers fed either with a standard diet or a MDD diet during gestation and lactation were compared. From a total of 44 000 probes for 26 456 genes, we found two gene clusters in MDD rats whose expression levels had significant differences compared with controls: 3269 overexpressed (p < 0.0009) and 2841 underexpressed (p < 0.0004) genes. Modifications of DNA methylation were found in the promoter regions of 1032 genes out of 14 981 genes. Ontological analyses revealed that these genes are mainly involved in glucose and lipid metabolism, nervous system, coagulation, ER stress, and mitochondrial function. Putative master genes exhibiting changes in both gene expression and DNA methylation are limited to 266 genes and are mainly involved in the renin-angiotensin system (n = 3), mitochondrion metabolism (n = 18), and phospholipid homeostasis (n = 3). Most of these master genes participate in nonalcoholic fatty liver disease. The adverse effects of MDD on the metabolic process indicate the beneficial impact of folate and vitamin B12, especially during the perinatal period. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Lactate: Friend or Foe.

    PubMed

    Hall, Mederic M; Rajasekaran, Sathish; Thomsen, Timothy W; Peterson, Andrew R

    2016-03-01

    Lactic acid has played an important role in the traditional theory of muscle fatigue and limitation of endurance exercise performance. It has been called a waste product of anaerobic metabolism and has been believed to be responsible for the uncomfortable "burn" of intense exercise and directly responsible for the metabolic acidosis of exercise, leading to decreased muscle contractility and ultimately cessation of exercise. Although this premise has been commonly taught, it is not supported by the scientific literature and has led to a great deal of confusion among the sports medicine and exercise science communities. This review will provide the sports medicine clinician with an understanding of contemporary lactate theories, including lactate's role in energy production, its contributions to metabolic acidosis, and its function as an energy substrate for a variety of tissues. Lactate threshold concepts will also be discussed, including a practical approach to understanding prediction of performance and monitoring of training progress based on these parameters.

  3. Contraception in lactating women.

    PubMed

    Díaz, S; Croxatto, H B

    1993-12-01

    Lactating women need contraception after first menses, supplementation or 6 months postpartum, or before, according to personal or programmatic reasons. Non-hormonal methods have no influence on lactation and are the first choice. Intrauterine devices (IUDs) inserted during amenorrhea are safe and show good continuation rates. Progestin-only methods do not affect breast-feeding and should be used after 6 weeks to prevent transference of orally active steroids to the newborn. Progesterone rings and Nestorone implants are effective new methods, that use orally inactive steroids.

  4. [Non-alcoholic fatty liver disease (NAFLD)].

    PubMed

    Rau, Monika; Weiss, Johannes; Geier, Andreas

    2015-07-01

    Non-alcoholic fatty liver disease is the most common chronic liver disease in Europe and in the USA with rising prevalence. Patients with a metabolic syndrome (diabetes mellitus, obesity, dyslipidemia) are patients at risk with the highest prevalence for NAFLD. Progression from a non-alcoholic fatty liver (NAFL) to a non-alcoholic steatohepatitis (NASH) occurs in 5-20% of patients with the potential to develop a liver fibrosis/cirrhosis. NASH patients and NAFLD patients with higher fibrosis should be identified because they are at risk of a higher mortality. A specific treatment for NASH is not available at the moment. Therefore, the treatment of risk factors and metabolic syndrome has high priority.

  5. Treatment of mastitis during lactation

    PubMed Central

    2009-01-01

    Treatment of mastitis should be based on bacteriological diagnosis and take national and international guidelines on prudent use of antimicrobials into account. In acute mastitis, where bacteriological diagnosis is not available, treatment should be initiated based on herd data and personal experience. Rapid bacteriological diagnosis would facilitate the proper selection of the antimicrobial. Treating subclinical mastitis with antimicrobials during lactation is seldom economical, because of high treatment costs and generally poor efficacy. All mastitis treatment should be evidence-based, i.e., the efficacy of each product and treatment length should be demonstrated by scientific studies. Use of on-farm written protocols for mastitis treatment promotes a judicious use of antimicrobials and reduces the use of antimicrobials. PMID:22081939

  6. [Pathogenetic substantiation of complex treatment of nonalcoholic steatohepatitis and steatosis in patients with pre-diabetes and type 2 diabetes].

    PubMed

    Чопей, Іван В; Івачевська, Віталіна В; Чубірко, Ксенія І; Гряділь, Тарас І; Гечко, Михайло М

    Thesis is devoted to the optimization of complex treatment of nonalcoholic steatohepatitis and steatosis in patients with pre-diabetes and type 2 diabetes by acting on carbohydrate and lipid metabolism as well as providing hepatoprotection. Optimization of diagnostics and treatment in patients treatment of nonalcoholic steatohepatitis and steatosis in patients with pre-diabetes and type 2 diabetes. Examination and treatment of 117 patients with NAFLD and pre-diabetes and type 2 diabetes was performed. It has been proved that the use of a therapeutic scheme that includes a balanced diet, taking into account the daily requirement in proteins, fats and carbohydrates, daily 30-minute walks at a brisk pace, rosuvastatin 10 mg/d, omega-3 PUFA 1000 mg/d and ursodeoxycholic acid 10 mg/kg/d in patients with NAFLD and pre-diabetes facilitates regression of signs of steatosis. In patients with NAFLD and type 2 diabetes the above mentioned therapeutic scheme including sitagliptin 100 mg/d promotes regression of steatohepatitis in steatosis. The prevalence of nonalcoholic steatohepatitis and liver steatosis in patients with pre-diabetes has been studied. It has been proved that patients with NAFLD and pre-diabetes belong to the group with high cardiovascular risk. The features of metabolic disorders in patients with nonalcoholic fatty liver disease and pre-diabetes or type 2 diabetes were researched. Differentiated treatment schemes of nonalcoholic steatosis and steatohepatitis in patients with pre-diabetes and type 2 diabetes have been approved for use.

  7. 21 CFR 184.1311 - Ferrous lactate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... with iron filings, reaction of ferrous chloride with sodium lactate, or reaction of ferrous sulfate... Substances Affirmed as GRAS § 184.1311 Ferrous lactate. (a) Ferrous lactate (iron (II) lactate, C6H10FeO6...

  8. 21 CFR 184.1311 - Ferrous lactate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Ferrous lactate. 184.1311 Section 184.1311 Food... Specific Substances Affirmed as GRAS § 184.1311 Ferrous lactate. (a) Ferrous lactate (iron (II) lactate.... It is prepared by reacting calcium lactate or sodium lactate with ferrous sulfate, direct reaction...

  9. 21 CFR 184.1311 - Ferrous lactate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Ferrous lactate. 184.1311 Section 184.1311 Food... GRAS § 184.1311 Ferrous lactate. (a) Ferrous lactate (iron (II) lactate, C6H10FeO6, CAS Reg. No. 5905... reacting calcium lactate or sodium lactate with ferrous sulfate, direct reaction of lactic acid with...

  10. 21 CFR 184.1311 - Ferrous lactate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Ferrous lactate. 184.1311 Section 184.1311 Food... Specific Substances Affirmed as GRAS § 184.1311 Ferrous lactate. (a) Ferrous lactate (iron (II) lactate.... It is prepared by reacting calcium lactate or sodium lactate with ferrous sulfate, direct reaction...

  11. 21 CFR 184.1311 - Ferrous lactate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Ferrous lactate. 184.1311 Section 184.1311 Food... Specific Substances Affirmed as GRAS § 184.1311 Ferrous lactate. (a) Ferrous lactate (iron (II) lactate.... It is prepared by reacting calcium lactate or sodium lactate with ferrous sulfate, direct reaction...

  12. Non-alcoholic fatty liver disease.

    PubMed

    Pearce, Lynne

    2016-08-24

    Essential facts Non-alcoholic fatty liver disease (NAFLD) is an excess of fat in the liver that is not the result of excessive alcohol consumption or other secondary causes, such as hepatitis C. According to the National Institute for Health and Care Excellence, fatty liver - steatosis - affects between 20% and 30% of the population and its prevalence is increasing.

  13. Laboratory Prototype of Bioreactor for Oxidation of Toxic D-Lactate Using Yeast Cells Overproducing D-Lactate Cytochrome c Oxidoreductase

    PubMed Central

    Karkovska, Maria

    2016-01-01

    D-lactate is a natural component of many fermented foods like yogurts, sour milk, cheeses, and pickles vegetable products. D-lactate in high concentrations is toxic for children and people with short bowel syndrome and provokes encephalopathy. These facts convincingly demonstrate a need for effective tools for the D-lactate removal from some food products. The main idea of investigation is focused on application of recombinant thermotolerant methylotrophic yeast Hansenula polymorpha “tr6,” overproducing D-lactate: cytochrome c oxidoreductase (EC 1.1.2.4, D-lactate cytochrome c oxidoreductase, D-lactate dehydrogenase (cytochrome), DLDH). In addition to 6-fold overexpression of DLDH under a strong constitutive promoter (prAOX), the strain of H. polymorpha “tr6” (gcr1 catX/Δcyb2, prAOX_DLDH) is characterized by impairment in glucose repression of AOX promoter, devoid of catalase and L-lactate-cytochrome c oxidoreductase activities. Overexpression of DLDH coupling with the deletion of L-lactate-cytochrome c oxidoreductase activity opens possibility for usage of the strain as a base for construction of bioreactor for removing D-lactate from fermented products due to oxidation to nontoxic pyruvate. A laboratory prototype of column-type bioreactor for removing a toxic D-lactate from model solution based on permeabilized cells of the H. polymorpha “tr6” and alginate gel was constructed and efficiency of this process was tested. PMID:27446952

  14. Lactate metabolism in acute uremia.

    PubMed

    Leverve, Xavier; Mustafa, Iqbal; Novak, Ivan; Krouzecky, Ales; Rokyta, Richard; Matejovic, Martin; Ichai, Carole

    2005-01-01

    Lactate is a key metabolite that is produced by every cell and oxidized by most of them, provided that they do contain mitochondria. Its metabolism is connected to energetic homeostasis and the cellular redox state. It is well recognized as an indicator of severe outcome in severely ill patients, however, it is not a detrimental factor per se. Conversely, some recent data tend even to indicate a beneficial effect in several metabolic disorders. Although the liver has long been recognized as a key organ in lactate homeostasis, the kidney also plays a major role as a gluconeogenic organ significantly involved in the glucose-lactate cycle. In acute renal failure, sodium lactate is widely used as a buffer in replacement fluids because the anion (lactate - ) is metabolized and the cation (Na + ) remains, leading to decreased water dissociation and proton concentration. The metabolic disorders related to acute renal failure or associated with it, such as liver failure, may affect lactate metabolism, and therefore they are often regarded as limiting factors for the use of lactate-containing fluids in such patients. By investigating endogenous lactate production in severe septic patients with acute renal failure, we found that an acute exogenous load of lactate did not affect the basal endogenous lactate production and metabolism. This indicates that exogenous lactate is well metabolized even in patients suffering from acute renal failure and severe sepsis with a compromised hemodynamic status.

  15. Popular Music Celebrity Endorsements in Food and Nonalcoholic Beverage Marketing.

    PubMed

    Bragg, Marie A; Miller, Alysa N; Elizee, Juleen; Dighe, Shatabdi; Elbel, Brian D

    2016-07-01

    Food and beverage marketing has been associated with childhood obesity. We quantified the number and type of food or beverage brands promoted by music celebrities, assessed the nutritional quality of the products, and examined Teen Choice Award data to assess the celebrities' popularity among adolescents. This was a descriptive study. A list of music celebrities associated with the 2013 and 2014 Billboard Hot 100 Chart, which ranks songs according to sales and radio impressions, was compiled. Data on celebrity endorsements were gathered from official company Web sites, YouTube commercials, an advertising database, and media reports. Nutritional quality of foods was assessed according to the Nutrient Profile Index, whereas nonalcoholic beverages were evaluated based on calories from added sugar. Teen Choice Award nominations were used to measure the celebrities' popularity among adolescents. Of the 590 endorsements made by the 163 celebrities in the sample, consumer goods (eg, fragrances, makeup) represented the largest endorsement category (26%), followed by food and beverage (18%) and retail (11%). Sixty-five celebrities were collectively associated with 57 different food and beverage brands owned by 38 parent companies. Of these 65 celebrities, 53 (81.5%) had ≥1 Teen Choice Award nomination. Forty-nine (71%) of the 69 nonalcoholic beverage references promoted sugar-sweetened beverages. Twenty-one (80.8%) of the 26 endorsed foods were energy dense and nutrient poor. Baauer, will.i.am, Justin Timberlake, Maroon 5, and Britney Spears had the most food and beverage endorsements. This study demonstrates that music celebrities who are popular among adolescents endorse energy-dense, nutrient-poor products. Copyright © 2016 by the American Academy of Pediatrics.

  16. Popular Music Celebrity Endorsements in Food and Nonalcoholic Beverage Marketing

    PubMed Central

    Miller, Alysa N.; Elizee, Juleen; Dighe, Shatabdi; Elbel, Brian D.

    2016-01-01

    BACKGROUND: Food and beverage marketing has been associated with childhood obesity. We quantified the number and type of food or beverage brands promoted by music celebrities, assessed the nutritional quality of the products, and examined Teen Choice Award data to assess the celebrities’ popularity among adolescents. METHODS: This was a descriptive study. A list of music celebrities associated with the 2013 and 2014 Billboard Hot 100 Chart, which ranks songs according to sales and radio impressions, was compiled. Data on celebrity endorsements were gathered from official company Web sites, YouTube commercials, an advertising database, and media reports. Nutritional quality of foods was assessed according to the Nutrient Profile Index, whereas nonalcoholic beverages were evaluated based on calories from added sugar. Teen Choice Award nominations were used to measure the celebrities’ popularity among adolescents. RESULTS: Of the 590 endorsements made by the 163 celebrities in the sample, consumer goods (eg, fragrances, makeup) represented the largest endorsement category (26%), followed by food and beverage (18%) and retail (11%). Sixty-five celebrities were collectively associated with 57 different food and beverage brands owned by 38 parent companies. Of these 65 celebrities, 53 (81.5%) had ≥1 Teen Choice Award nomination. Forty-nine (71%) of the 69 nonalcoholic beverage references promoted sugar-sweetened beverages. Twenty-one (80.8%) of the 26 endorsed foods were energy dense and nutrient poor. Baauer, will.i.am, Justin Timberlake, Maroon 5, and Britney Spears had the most food and beverage endorsements. CONCLUSIONS: This study demonstrates that music celebrities who are popular among adolescents endorse energy-dense, nutrient-poor products. PMID:27273712

  17. Nonalcoholic steatohepatitis and hepatocellular carcinoma: Brazilian survey

    PubMed Central

    Cotrim, Helma P.; Oliveira, Claudia P.; Coelho, Henrique Sérgio M.; Alvares-da-Silva, Mario R.; Nabuco, Leticia; Parise, Edison Roberto; Ivantes, Claúdia; Martinelli, Ana LC; Galizzi-Filho, João; Carrilho, Flair J.

    2016-01-01

    OBJECTIVE: The majority of cases of hepatocellular carcinoma have been reported in individuals with cirrhosis due to chronic viral hepatitis and alcoholism, but recently, the prevalence has become increasingly related to nonalcoholic steatohepatitis around the world. The study aimed to evaluate the clinical and histophatological characteristics of hepatocellular carcinoma in Brazilians' patients with nonalcoholic steatohepatitis at the present time. METHODS: Members of the Brazilian Society of Hepatology were invited to complete a survey regarding patients with hepatocellular carcinoma related to nonalcoholic steatohepatitis. Patients with a history of alcohol intake (>20 g/day) and other liver diseases were excluded. Hepatocellular carcinoma diagnosis was performed by liver biopsy or imaging methods according to the American Association for the Study of Liver Diseases' 2011 guidelines. RESULTS: The survey included 110 patients with a diagnosis of hepatocellular carcinoma and nonalcoholic fatty liver disease from nine hepatology units in six Brazilian states (Bahia, Minas Gerais, Rio de Janeiro, São Paulo, Paraná and Rio Grande do Sul). The mean age was 67±11 years old, and 65.5% were male. Obesity was observed in 52.7% of the cases; diabetes, in 73.6%; dyslipidemia, in 41.0%; arterial hypertension, in 60%; and metabolic syndrome, in 57.2%. Steatohepatitis without fibrosis was observed in 3.8% of cases; steatohepatitis with fibrosis (grades 1-3), in 27%; and cirrhosis, in 61.5%. Histological diagnosis of hepatocellular carcinoma was performed in 47.2% of the patients, with hepatocellular carcinoma without cirrhosis accounting for 7.7%. In total, 58 patients with cirrhosis had their diagnosis by ultrasound confirmed by computed tomography or magnetic resonance imaging. Of these, 55% had 1 nodule; 17%, 2 nodules; and 28%, ≥3 nodules. CONCLUSIONS: Nonalcoholic steatohepatitis is a relevant risk factor associated with hepatocellular carcinoma in patients with and

  18. A comparative proteomic analysis of Bacillus coagulans in response to lactate stress during the production of L-lactic acid.

    PubMed

    Wang, Xiuwen; Qin, Jiayang; Wang, Landong; Xu, Ping

    2014-12-01

    The growth rate and maximum biomass of Bacillus coagulans 2-6 were inhibited by lactate; inhibition by sodium lactate was stronger than by calcium lactate. The differences of protein expressions by B. coagulans 2-6 under the lactate stress were determined using two-dimensional electrophoresis coupled with mass spectrometric identification. Under the non-stress condition, calcium lactate stress and sodium lactate stress, the number of detected protein spots was 1,571 ± 117, 1,281 ± 231 and 904 ± 127, respectively. Four proteins with high expression under lactate stress were identified: lactate dehydrogenase, cysteine synthase A, aldo/keto reductase and ribosomal protein L7/L12. These proteins are thus potential targets for the reconstruction of B. coagulans to promote its resistance to lactate stress.

  19. Current issues in lactation: advantages, environment, silicone.

    PubMed

    Kacew, S

    1994-12-01

    The physiological process of breast-feeding should be encouraged under most circumstances despite the presence of trace amounts of environmental toxins. The decision for the initiation and continuation of lactation must involve the expectant father, especially in the provision of knowledge by clinicians of the beneficial effects to infant and mother. Awareness that growth patterns of breast-fed infants differ from formula-feeding is essential in the interpretation of toxicity and not an indicator to terminate lactation. Numerous studies demonstrate the importance of breast-feeding in providing protection against various diseases and decreasing the incidence of infant morbidity and mortality. Inert material such as silicone or environmental toxins including organophosphate pesticides, chlorinated hydrocarbons, solvents, and heavy metals have been identified in human milk. Toxic manifestations were reported in suckling infants exposed to mammary chemicals. The observed adverse reactions were suggested to be due to either (1) a direct action of the chemical without any maternal dietary deficiency, (2) a combination of essential mother nutrient deficiency and excess toxicant in breast milk; or (3) the presence of several toxicants in human milk acting in conjunction as bioactivators or promoters of toxicity. In weighing the risks vs benefits of lactation there is a clear consensus that even in the presence of mammary toxicants, breast-feeding should be promoted and maintained.

  20. Lactate in bitches with pyometra.

    PubMed

    Volpato, R; Rodello, L; Abibe, R B; Lopes, M D

    2012-12-01

    Lactate is a compound produced by the anaerobic metabolism of glucose, and hyperlactataemia occurs when the rate of production of lactate exceeds the rate of elimination. This occurs in situations of hypoxia and tissue hypoperfusion. Lactate has been considered a useful prognostic indicator in critically ill patients. Pyometra is a disease of adult female dogs characterized by inflammation of the uterus with an accumulation of exudate, which occurs during the luteal phase. It is one of the most common diseases that occur in the genital tract of female dogs. A total of 31 dogs were diagnosed with pyometra. The diagnosis was confirmed at ultrasonography. Of the 31 dogs, 25 females had open cervix pyometra and six had closed cervix pyometra. Plasma lactate concentrations were determined by an enzymatic colorimetric method. The average concentration (±SD) of plasma lactate in all 31 bitches with pyometra was 3.55 ± 0.46 mm. Healthy dogs had plasma lactate concentrations between 0.3 and 2.5 mm (mean ± SD). Concentrations ranged from 0.8 to 2.9 mm when plasma lactate was measured with a portable device and 0.4-2.6 mm with the blood gas analyser. Even though plasma lactate values vary between several studies and equipment used to measure concentrations, our results for dogs with pyometra are higher indicating hyperlactataemia (Thorneloe et al. , Can Vet J 48, 283-288). Plasma lactate in dogs with closed cervix pyometra was mean ± SD and in dogs with open cervix pyometra, it was mean ± SD. The plasma lactate concentration in dogs with pyometra was higher than in healthy bitches, and there was no influence of patency of the cervix on the concentration of plasma lactate concentrations. Plasma lactate concentrations were similar for animals with open and closed pyometra (3.54 ± 0.52 to 3.64 ± 1.03 mm).

  1. Nonalcoholic Fatty Liver Disease in Pediatrics.

    PubMed

    Duncan, Martin; Zong, Wenjing; Biank, Vincent F; Hageman, Joseph R

    2016-02-01

    A 16-year-old Hispanic girl with an elevated body mass index in an otherwise normal state of health presented for her well-child examination. She had signs of metabolic syndrome and insulin resistance including increased waist circumference and acanthosis nigricans. Laboratory results revealed elevated transaminases with otherwise normal hepatic function. Based on the physical examination and laboratory results, she was diagnosed with nonalcoholic fatty liver disease (NAFLD). After further evaluation, she eventually underwent a liver biopsy. The biopsy revealed nonalcoholic steatohepatitis (NASH) with stage 2 fibrosis. This article reviews the definition of NAFLD and NASH, an increasingly prevalent cause of pediatric chronic liver disease associated with obesity and metabolic syndrome. The article also outlines the epidemiology, risk factors, and natural history of NAFLD, which may help identify and prevent high-risk pediatric patients from progressing to irreversible liver disease. Understanding the diagnostic and treatment options offers the best chance at preventing and reversing the early stages of this disease.

  2. Pediatric Non-alcoholic Fatty Liver Disease.

    PubMed

    Uppal, Vikas; Mansoor, Sana; Furuya, Katryn N

    2016-05-01

    Childhood obesity has reached epidemic proportions, and by 2012, more than one third of American children were overweight or obese. As a result, increasingly, children are developing complications of obesity including liver disease. In fact, non-alcoholic fatty liver disease is the most common form of chronic liver disease seen in children today. Recently, there has been a burgeoning literature examining the pathogenesis, genetic markers, and role of the microbiome in this disease. On the clinical front, new modalities of diagnosing hepatic steatosis and hepatic fibrosis are being developed to provide non-invasive methods of surveillance in children. Lastly, the mainstay of treatment of pediatric non-alcoholic fatty liver disease (NAFLD) has been largely through lifestyle interventions, namely, dieting and exercise. Currently, there are a number of clinical trials examining novel lifestyle and drug therapies for NAFLD that are registered with the US National Institutes of Health ClinicalTrials.gov website.

  3. Micronutrient Antioxidants and Nonalcoholic Fatty Liver Disease.

    PubMed

    Chen, Guanliang; Ni, Yinhua; Nagata, Naoto; Xu, Liang; Ota, Tsuguhito

    2016-08-23

    Nonalcoholic fatty liver disease (NAFLD) is one of the most important chronic liver diseases worldwide and has garnered increasing attention in recent decades. NAFLD is characterized by a wide range of liver changes, from simple steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. The blurred pathogenesis of NAFLD is very complicated and involves lipid accumulation, insulin resistance, inflammation, and fibrogenesis. NAFLD is closely associated with complications such as obesity, diabetes, steatohepatitis, and liver fibrosis. During the progression of NAFLD, reactive oxygen species (ROS) are activated and induce oxidative stress. Recent attempts at establishing effective NAFLD therapy have identified potential micronutrient antioxidants that may reduce the accumulation of ROS and finally ameliorate the disease. In this review, we present the molecular mechanisms involved in the pathogenesis of NAFLD and introduce some dietary antioxidants that may be used to prevent or cure NAFLD, such as vitamin D, E, and astaxanthin.

  4. Nonalcoholic steatohepatitis and insulin resistance in children

    PubMed Central

    Arata, Mikage; Nakajima, Junya; Nishimata, Shigeo; Nagata, Tomomi; Kawashima, Hisashi

    2014-01-01

    Various pathological conditions can cause fatty liver in children. Nonalcoholic steatohepatitis (NASH) in children has been known since 1983. However, NASH diagnosed in childhood does not have a favorable outcome. The pathological characteristics of NASH are significantly different between children and adults. Nonalcoholic fatty liver disease (NAFLD)/NASH is accompanied by insulin resistance, which plays a pivotal role in its pathophysiology in both children and adults. In NASH, a “two-hit” model involving triglyceride accumulation (first hit) and liver damage (second hit) has been accepted. Insulin resistance was found to correlate with changes in fat levels; however, it did not correlate with fibrosis or NAFLD activity score in children. Therefore, insulin resistance may be important in the first hit. Because there is obvious familial clustering in NASH, genetic predisposition as well as environmental factors including diet might be the second hit of NAFLD/NASH. PMID:25512797

  5. Genetic predisposition in nonalcoholic fatty liver disease

    PubMed Central

    Sookoian, Silvia; Pirola, Carlos J.

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease whose prevalence has reached global epidemic proportions. Although the disease is relatively benign in the early stages, when severe clinical forms, including nonalcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma, occur, they result in worsening the long-term prognosis. A growing body of evidence indicates that NAFLD develops from a complex process in which many factors, including genetic susceptibility and environmental insults, are involved. In this review, we focused on the genetic component of NAFLD, with special emphasis on the role of genetics in the disease pathogenesis and natural history. Insights into the topic of the genetic susceptibility in lean individuals with NAFLD and the potential use of genetic tests in identifying individuals at risk are also discussed. PMID:28268262

  6. Micronutrient Antioxidants and Nonalcoholic Fatty Liver Disease

    PubMed Central

    Chen, Guanliang; Ni, Yinhua; Nagata, Naoto; Xu, Liang; Ota, Tsuguhito

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most important chronic liver diseases worldwide and has garnered increasing attention in recent decades. NAFLD is characterized by a wide range of liver changes, from simple steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. The blurred pathogenesis of NAFLD is very complicated and involves lipid accumulation, insulin resistance, inflammation, and fibrogenesis. NAFLD is closely associated with complications such as obesity, diabetes, steatohepatitis, and liver fibrosis. During the progression of NAFLD, reactive oxygen species (ROS) are activated and induce oxidative stress. Recent attempts at establishing effective NAFLD therapy have identified potential micronutrient antioxidants that may reduce the accumulation of ROS and finally ameliorate the disease. In this review, we present the molecular mechanisms involved in the pathogenesis of NAFLD and introduce some dietary antioxidants that may be used to prevent or cure NAFLD, such as vitamin D, E, and astaxanthin. PMID:27563875

  7. Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) in HIV.

    PubMed

    Rockstroh, Jürgen Kurt

    2017-04-01

    Abnormal liver enzymes (LE) are common in patients infected with the human immunodeficiency virus (HIV) even in the absence of viral hepatitis or alcohol abuse. With availability of antiretroviral combination therapy, life expectancy has improved dramatically and as a consequence the spectrum of liver disease is changing. Increased reports on the development of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) in HIV coinfected patients raise questions around prevalence, clinical manifestations, and clinical outcome of these liver diseases in HIV coinfection. Moreover, the potential impact of combination antiretroviral therapy as well as direct HIV effects on the emergence of non-alcoholic fatty liver disease needs to be explored. This review summarizes the recent literature on NAFLD and NASH in HIV.

  8. Extrahepatic Complications of Nonalcoholic Fatty Liver Disease.

    PubMed

    Chacko, Kristina R; Reinus, John

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is an important cause of liver disease that is often associated with the metabolic syndrome. There is a growing awareness that extrahepatic complications occur in individuals with NAFLD, especially an increased risk of cardiovascular disease. Development of diabetes mellitus, chronic kidney disease, colorectal cancer, and endocrinopathies has been linked to NAFLD. This article reviews the extrahepatic complications affecting individuals with NAFLD and the pathogenesis underlying their development. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Contraceptive implants and lactation.

    PubMed

    Díaz, Soledad

    2002-01-01

    The safety and efficacy of four contraceptive implants, plant, Implanon, Nestorone and Elcometrine, have been evaluated during use in the postpartum period by lactating women. These implants provide highly effective contraceptive protection with no negative effect on breastfeeding or infant growth and development. Breastfeeding women initiating Norplant use in the second postpartum month experience significantly longer periods of amenorrhea than do untreated women or intrauterine device users. After weaning, the bleeding pattern is similar to that observed in non-nursing women. Norplant use does not affect bone turnover and density during lactation. Norplant and Implanon release orally active progestins while Nestorone and Elcometrine implants release an orally inactive progestin, which represents an advantage since the infant should be free of steroidal effects. The infant's daily intake of steroids (estimated from concentrations in maternal milk during the first month of use) range from 90 to 100 ng of levonorgestrel (Norplant), 75-120 ng of etonogestrel (Implanon), and 50 ng and 110 ng of Nestorone (Nestorone and Elcometrine implants, respectively). Nursing women needing contraception may use progestin-only implants when nonhormonal methods are not available or acceptable. Implants that deliver orally active steroids should only be used after 6 weeks postpartum to avoid transferring of steroids to the newborn.

  10. Non-alcoholic fatty liver disease.

    PubMed

    Neuschwander-Tetri, Brent A

    2017-02-28

    Non-alcoholic fatty liver disease has emerged a major challenge because of it prevalence, difficulties in diagnosis, complex pathogenesis, and lack of approved therapies. As the burden of hepatitis C abates over the next decade, non-alcoholic fatty liver disease will become the major form of chronic liver disease in adults and children and could become the leading indication for liver transplantation. This overview briefly summarizes the most recent data on the pathophysiology, diagnosis, and treatment of non-alcoholic fatty liver disease. Ongoing clinical trials are focused on an array of disease mechanisms and reviewed here are how these treatments fit into the current paradigm of substrate overload lipotoxic liver injury. Many of the approaches are directed at downstream events such as inflammation, injury and fibrogenesis. Addressing more proximal processes such as dysfunctional satiety mechanisms and inappropriately parsimonious energy dissipation are potential therapeutic opportunities that if successfully understood and exploited would not only address fatty liver disease but also the other components of the metabolic syndrome such as obesity, diabetes and dyslipidemia.

  11. Therapies in non-alcoholic steatohepatitis (NASH).

    PubMed

    Oseini, Abdul M; Sanyal, Arun J

    2017-01-01

    The hallmark of non-alcoholic fatty liver disease (NAFLD) is excessive fatty accumulation in the hepatocytes, which may be an isolated event (non-alcoholic fatty liver, NAFL) or accompanied by evidence of inflammation and cell injury with or without fibrosis (non-alcoholic steatohepatitis, NASH). NASH, the more aggressive form of NAFLD, may progress to cirrhosis and hepatocellular carcinoma. Since NASH is estimated to overtake hepatitis C virus infection as the leading cause of liver transplantation in the US in the coming decade, and there are no current FDA-approved therapies for this disease, the need to find appropriate therapeutic targets is now more urgent than ever before. Diet and other lifestyle modifications have always been difficult to maintain and this approach alone has not slowed the rising tide of the disease. While the results of traditional therapies such as vitamin E and pioglitazone have been significant for steatosis and inflammation, they have had no effect on fibrosis, which is the strongest indicator of mortality in this condition. However, the understanding of the pathogenesis and progression of NASH has evolved and several promising novel therapies to target and possibly reverse fibrosis are being evaluated, making the future outlook of NASH therapy more optimistic.

  12. Local Treatment with Lactate Prevents Intestinal Inflammation in the TNBS-Induced Colitis Model

    PubMed Central

    Iraporda, Carolina; Romanin, David E.; Bengoa, Ana A.; Errea, Agustina J.; Cayet, Delphine; Foligné, Benoit; Sirard, Jean-Claude; Garrote, Graciela L.; Abraham, Analía G.; Rumbo, Martín

    2016-01-01

    Lactate has long been considered as a metabolic by-product of cells. Recently, this view has been changed by the observation that lactate can act as a signaling molecule and regulates critical functions of the immune system. We previously identified lactate as the component responsible for the modulation of innate immune epithelial response of fermented milk supernatants in vitro. We have also shown that lactate downregulates proinflammatory responses of macrophages and dendritic cells. So far, in vivo effects of lactate on intestinal inflammation have not been reported. We evaluated the effect of intrarectal administration of lactate in a murine model of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). The increase in lactate concentration in colon promoted protective effects against TNBS-induced colitis preventing histopathological damage, as well as bacterial translocation and rise of IL-6 levels in serum. Using intestinal epithelial reporter cells, we found that flagellin treatment induced reporter gene expression, which was abrogated by lactate treatment as well as by glycolysis inhibitors. Furthermore, lactate treatment modulated glucose uptake, indicating that high levels of extracellular lactate can impair metabolic reprograming induced by proinflammatory activation. These results suggest that lactate could be a potential beneficial microbiota metabolite and may constitute an overlooked effector with modulatory properties. PMID:28082985

  13. Local Treatment with Lactate Prevents Intestinal Inflammation in the TNBS-Induced Colitis Model.

    PubMed

    Iraporda, Carolina; Romanin, David E; Bengoa, Ana A; Errea, Agustina J; Cayet, Delphine; Foligné, Benoit; Sirard, Jean-Claude; Garrote, Graciela L; Abraham, Analía G; Rumbo, Martín

    2016-01-01

    Lactate has long been considered as a metabolic by-product of cells. Recently, this view has been changed by the observation that lactate can act as a signaling molecule and regulates critical functions of the immune system. We previously identified lactate as the component responsible for the modulation of innate immune epithelial response of fermented milk supernatants in vitro. We have also shown that lactate downregulates proinflammatory responses of macrophages and dendritic cells. So far, in vivo effects of lactate on intestinal inflammation have not been reported. We evaluated the effect of intrarectal administration of lactate in a murine model of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). The increase in lactate concentration in colon promoted protective effects against TNBS-induced colitis preventing histopathological damage, as well as bacterial translocation and rise of IL-6 levels in serum. Using intestinal epithelial reporter cells, we found that flagellin treatment induced reporter gene expression, which was abrogated by lactate treatment as well as by glycolysis inhibitors. Furthermore, lactate treatment modulated glucose uptake, indicating that high levels of extracellular lactate can impair metabolic reprograming induced by proinflammatory activation. These results suggest that lactate could be a potential beneficial microbiota metabolite and may constitute an overlooked effector with modulatory properties.

  14. [Non-alcoholic fatty liver disease (NAFLD) /non-alcoholic steatohepatitis (NASH) and nutrition].

    PubMed

    Ishii, Kiyo-aki; Takamura, Toshinari

    2016-03-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation in the form of triglycerides in the hepatocytes. A more severe form of NAFLD with necrosis, inflammation, and fibrosis is called non-alcoholic steatohepatitis (NASH). The liver is located in the center of the body's organ network and acts as a coordinator of glucose and lipid metabolism. Therefore, it is important to perform nutritional therapy of patients with NAFLD/NASH while maintaining the energy balance in the entire body.

  15. Current treatment options for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

    PubMed

    Beaton, Melanie D

    2012-06-01

    Nonalcoholic fatty liver disease is the leading cause of liver disease in western society. It is a cause of end-stage liver disease, with increased mortality secondary to cirrhosis and its complications. It is also recognized that cardiovascular disease is a significant cause of death in these patients. Significant work evaluating various treatments has been performed in recent years; however, to date, no ideal therapy exists. Lifestyle modification remains the cornerstone of management. The present article reviews the current status of various treatment modalities evaluated in nonalcoholic fatty liver disease.

  16. Histology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis in Adults and Children.

    PubMed

    Kleiner, David E; Makhlouf, Hala R

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is the liver disease associated with obesity, diabetes, and the metabolic syndrome. Although steatosis is a key histologic feature, liver biopsies of patients with NAFLD can show a wide range of findings. Nonalcoholic steatohepatitis (NASH) is a progressive subtype of NAFLD first defined by analogy to alcoholic hepatitis. Young children may have an alternate pattern of progressive NAFLD characterized by a zone 1 distribution of steatosis, inflammation, and fibrosis. Several grading and staging systems exist, but all require adequate biopsies. Although NASH generally shows fibrosis progression over time, some patients show regression of disease.

  17. Liver steatosis and nonalcoholic steatohepatitis: from pathogenesis to therapy.

    PubMed

    Hernández-Pérez, Elizabeth; León García, Plácido Enrique; López-Díazguerrero, Norma Edith; Rivera-Cabrera, Fernando; Del Ángel Benítez, Elizabeth

    2016-09-13

    Non-alcoholic fatty liver disease refers to a disease spectrum that ranges from steatosis to non-alcoholic steatohepatitis, which leads to fibrosis, cirrhosis and hepatocellular carcinoma. Given the increasing prevalence of obesity worldwide, the incidence of non-alcoholic fatty liver disease has become a world health problem. Non-alcoholic fatty liver disease is considered to be the hepatic manifestation of metabolic syndrome associated with insulin resistance, central obesity, and type 2 diabetes mellitus. Allegedly, insulin resistance plays a pivotal role in its pathogenesis. Here we highlight non-alcoholic fatty liver disease epidemiology and pathophysiology, its progression towards steatohepatitis with particular emphasis in liver fibrosis and participation of advanced glycation end products. The different treatments reported are described here as well. We conducted a search in PubMed with the terms steatohepatitis, steatosis advanced glycation end products, liver fibrosis and adipocytokines. Articles were selected according to their relevance.

  18. Nonalcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis in Childhood: Endocrine-Metabolic “Mal-Programming”

    PubMed Central

    Manti, Sara; Romano, Claudio; Chirico, Valeria; Filippelli, Martina; Cuppari, Caterina; Loddo, Italia; Salpietro, Carmelo; Arrigo, Teresa

    2014-01-01

    Context: Nonalcoholic Fatty Liver Disease (NAFLD) is the major chronic liver disease in the pediatric population. NAFLD includes a broad spectrum of abnormalities (inflammation, fibrosis and cirrhosis), ranging from accumulation of fat (also known as steatosis) towards non-alcoholic steatohepatitis (NASH). The development of NAFLD in children is significantly increased. Evidence Acquisition: A literature search of electronic databases was undertaken for the major studies published from 1998 to today. The databases searched were: PubMed, EMBASE, Orphanet, Midline and Cochrane Library. We used the key words: "non-alcoholic fatty liver disease, children, non-alcoholic steatohepatitis and fatty liver". Results: NAFLD/NASH is probably promoted by “multiple parallel hits”: environmental and genetic factors, systemic immunological disorders (oxidative stress, persistent-low grade of inflammation) as well as obesity and metabolic alterations (insulin resistance and metabolic syndrome). However its exact cause still underdiagnosed and unknown. Conclusions: Pediatric NAFLD/NASH is emerging problem. Longitudinal follow-up studies, unfortunately still insufficient, are needed to better understand the natural history and outcome of NAFLD in children. This review focuses on the current knowledge regarding the epidemiology, pathogenesis, environmental, genetic and metabolic factors of disease. The review also highlights the importance of studying the underlying mechanisms of pediatric NAFLD and the need for complete and personalized approach in the management of NAFLD/NASH. PMID:24829591

  19. Probiotics as a novel treatment for non-alcoholic Fatty liver disease; a systematic review on the current evidences.

    PubMed

    Kelishadi, Roya; Farajian, Sanam; Mirlohi, Maryam

    2013-04-01

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, with 5-10% of liver having extra fat. Increase in its prevalence in all age groups is linked with obesity and Type II diabetes. The treatment of NAFLD remains controversial. A growing body of evidence suggests a relation between overgrowth of gut microbiota with NAFLD and non-alcoholic steatohepatitis (NASH). The objective of this review is to provide an overview on experimental and clinical studies assessing all positive and negative effects of probiotics. We made a critical appraisal on various types of documents published from 1999 to March 2012 in journals, electronic books, seminars, and symposium contexts including Medline, PubMed, and Cochrane Central Register of Controlled Trials databases. We used the key words: "non-alcoholic fatty liver disease, probiotics, non-alcoholic steatohepatitis, liver disease, and fatty liver". Probiotics, as biological factors, control the gut microbiota and result in its progression. It is in this sense that they are suggestive of a new and a natural way of promoting liver function. Correspondingly, limited evidence suggests that probiotics could be considered as a new way of treatment for NAFLD. Various experimental studies and clinical trials revealed promising effects of probiotics in improving NAFLD; however given the limited experience in this field, generalization of probiotics as treatment of NAFLD needs substantiation through more trials with a larger sample sizes and with longer-term follow up.

  20. Antagonism of V1b receptors promotes maternal motivation to retrieve pups in the MPOA and impairs pup-directed behavior during maternal defense in the mpBNST of lactating rats.

    PubMed

    Bayerl, Doris S; Kaczmarek, Veronika; Jurek, Benjamin; van den Burg, Erwin H; Neumann, Inga D; Gaßner, Barbara M; Klampfl, Stefanie M; Bosch, Oliver J

    2016-03-01

    Recent studies using V1b receptor (V1bR) knockout mice or central pharmacological manipulations in lactating rats highlighted the influence of this receptor for maternal behavior. However, its role in specific brain sites known to be important for maternal behavior has not been investigated to date. In the present study, we reveal that V1bR mRNA (qPCR) and protein levels (Western blot) within either the medial preoptic area (MPOA) or the medial-posterior part of the bed nucleus of the stria terminalis (mpBNST) did not differ between virgin and lactating rats. Furthermore, we characterized the effects of V1bR blockade via bilateral injections of the receptor subtype-specific antagonist SSR149415 within the MPOA or the mpBNST on maternal behavior (maternal care under non-stress and stress conditions, maternal motivation to retrieve pups in a novel environment, maternal aggression) and anxiety-related behavior in lactating rats. Blocking V1bR within the MPOA increased pup retrieval, whereas within the mpBNST it decreased pup-directed behavior, specifically licking/grooming the pups, during the maternal defense test. In addition, immediately after termination of the maternal defense test, V1bR antagonism in both brain regions reduced nursing, particularly arched back nursing. Anxiety-related behavior was not affected by V1bR antagonism in either brain region. In conclusion our data indicate that V1bR antagonism significantly modulates different aspects of maternal behavior in a brain region-dependent manner.

  1. Metabolic Control of Anaerobic Glycolysis (Overexpression of Lactate Dehydrogenase in Transgenic Tomato Roots Supports the Davies-Roberts Hypothesis and Points to a Critical Role for Lactate Secretion.

    PubMed

    Rivoal, J.; Hanson, A. D.

    1994-11-01

    Roots of all plants examined so far have the potential for both ethanol and lactate fermentation. A short burst of lactate fermentation usually occurs when plant tissues are transferred from normoxic to anoxic conditions. According to the Davies-Roberts hypothesis, the consequent pH drop both initiates ethanol fermentation and blocks further production of lactate by inhibiting lactate dehydrogenase (LDH). However, the role of LDH in this pH control mechanism is still a matter of debate. To perturb the control system in a defined way, a barley LDH cDNA under the control of the cauliflower mosaic virus 35S promoter was introduced into tomato (Lycopersicon esculentum Mill. cv VFMT) using Agrobacterium rhizogenes. The transgenic root clones expressed up to 50 times the LDH activity of controls. The fermentative metabolism of these clones was compared using roots grown previously in normoxic conditions or roots given a 3-d hypoxic pretreatment. During the transition from normoxia to anoxia, lactate accumulation was no faster and no more extensive in transgenic roots than in controls. Similarly, during prolonged anoxia the flux of 14C from [U-14C] glucose to lactate and ethanol was not modified by the expression of the transgene. However, in both transgenic and control roots, hypoxic pretreatment increased the flux to lactate and promoted lactate export to the medium. These results show that LDH has a very low flux control coefficient for lactate fermentation, consistent with the Davies-Roberts hypothesis. Moreover, they suggest that lactate secretion exerts major control over long-term lactate glycolysis in vivo.

  2. Lactate and lactate clearance in acute cardiac care patients

    PubMed Central

    Lazzeri, Chiara; Picariello, Claudio; Dini, Carlotta Sorini; Gensini, Gian Franco; Valente, Serafina

    2012-01-01

    Hyperlactataemia is commonly used as a diagnostic and prognostic tool in intensive care settings. Recent studies documented that serial lactate measurements over time (or lactate clearance), may be clinically more reliable than lactate absolute value for risk stratification in different pathological conditions. While the negative prognostic role of hyperlactataemia in several critical ill diseases (such as sepsis and trauma) is well established, data in patients with acute cardiac conditions (i.e. acute coronary syndromes) are scarce and controversial. The present paper provides an overview of the current available evidence on the clinical role of lactic acid levels and lactate clearance in acute cardiac settings (acute coronary syndromes, cardiogenic shock, cardiac surgery), focusing on its prognostic role. PMID:24062898

  3. Induction of triglyceride accumulation and mitochondrial maintenance in muscle cells by lactate

    PubMed Central

    Sun, Jingquan; Ye, Xin; Xie, Minhao; Ye, Jianping

    2016-01-01

    Muscle exercise induces intramuscular triglyceride (TG) accumulation and promotes mitochondrial maintenance in myotubes. However, the mechanism underlying exercise effects remains unknown. In this study, lactic acid was tested as a signaling molecule in C2C12 myotubes to understand the mechanism. Intracellular TG storage was induced in the cells by sodium lactate. The lactate activity was observed with an inhibition of the cAMP-PKA pathway as indicated by a reduction in the phosphorylation status of CREB (pCREB). Induction of pCREB signal by forskolin was blocked by pretreatment of cells with lactate. The impact of lactate on mitochondrial function was examined with a focus on the activities of two enzymes, MCAT (malonylCoA:ACP transferase) and PDH (pyruvate dehydrogenase). The enzyme activities were induced in the cells by lactate. Expression of the lactate receptor (GPR81) and lactate transporters (MCT1/4) were induced as well by lactate. The lactate activities were observed at concentrations between 4–64 mM, and were not dependent on the increase in intracellular pyruvate. Pyruvate treatment did not generate the same effects in the cells. Those results suggest that lactate may induce intramuscular TG storage and mitochondrial maintenance in myotubes through inhibition of the cAMP pathway by activation of GPR81 in a positive feedback manner. PMID:27645401

  4. Managing non-alcoholic fatty liver disease

    PubMed Central

    Ngu, Jing Hieng; Goh, George Boon Bee; Poh, Zhongxian; Soetikno, Roy

    2016-01-01

    The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly with the obesity and diabetes mellitus epidemics. It is rapidly becoming the most common cause of liver disease worldwide. NAFLD can progress to serious complications such as cirrhosis, hepatocellular carcinoma and death. Therefore, it is important to recognise this condition so that early intervention can be implemented. Lifestyle modifications and strict control of metabolic risk factors are the mainstay of treatment. As disease progression is slow in the majority of NAFLD patients, most can be managed well by primary care physicians. NAFLD patients with advanced liver fibrosis should be referred to specialist care for further assessment. PMID:27439352

  5. Maternal high-fat intake predisposes nonalcoholic fatty liver disease in C57BL/6 offspring.

    PubMed

    Gregorio, Bianca M; Souza-Mello, Vanessa; Carvalho, Jorge J; Mandarim-de-Lacerda, Carlos A; Aguila, Marcia B

    2010-11-01

    This work aimed to verify the hypothesis that maternal intake of high-fat diet in critical periods of pregnancy and/or suckling period predisposes nonalcoholic fatty liver disease in adult C57BL/6 mice offspring. Male pups were divided into 5 groups: (1) SC, from standard chow-fed dams; (2) G, from high-fat chow (HF)-fed dams during the gestation (G) period; (3) L, from HF-fed dams during the lactation (L) period; (4) GL, from HF-fed dams during the gestation and lactation (GL) periods; and (5) GL/HF, from HF-fed dams during GL, maintaining an HF diet from postweaning to adulthood. We analyzed body mass, plasma blood, and liver structure. The G offspring showed insulin resistance and lower glucose transporter-2 expression. Hepatic steatosis was present in the G, L, GL, and mainly in GL/HF offspring. Sterol regulatory element-binding protein-1c expression was higher in G, GL, and GL/HF offspring. Programming by HF chow predisposes hepatic adverse remodeling in the liver of adult offspring. Copyright © 2010 Mosby, Inc. All rights reserved.

  6. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis.

    PubMed

    Tilg, Herbert; Moschen, Alexander R

    2010-11-01

    Whereas in most cases a fatty liver remains free of inflammation, 10%-20% of patients who have fatty liver develop inflammation and fibrosis (nonalcoholic steatohepatitis [NASH]). Inflammation may precede steatosis in certain instances. Therefore, NASH could reflect a disease where inflammation is followed by steatosis. In contrast, NASH subsequent to simple steatosis may be the consequence of a failure of antilipotoxic protection. In both situations, many parallel hits derived from the gut and/or the adipose tissue may promote liver inflammation. Endoplasmic reticulum stress and related signaling networks, (adipo)cytokines, and innate immunity are emerging as central pathways that regulate key features of NASH.

  7. Nonalcoholic fatty liver disease: a precursor of the metabolic syndrome.

    PubMed

    Lonardo, Amedeo; Ballestri, Stefano; Marchesini, Giulio; Angulo, Paul; Loria, Paola

    2015-03-01

    The conventional paradigm of nonalcoholic fatty liver disease representing the "hepatic manifestation of the metabolic syndrome" is outdated. We identified and summarized longitudinal studies that, supporting the association of nonalcoholic fatty liver disease with either type 2 diabetes mellitus or metabolic syndrome, suggest that nonalcoholic fatty liver disease precedes the development of both conditions. Online Medical databases were searched, relevant articles were identified, their references were further assessed and tabulated data were checked. Although several cross-sectional studies linked nonalcoholic fatty liver disease to either diabetes and other components of the metabolic syndrome, we focused on 28 longitudinal studies which provided evidence for nonalcoholic fatty liver disease as a risk factor for the future development of diabetes. Moreover, additional 19 longitudinal reported that nonalcoholic fatty liver disease precedes and is a risk factor for the future development of the metabolic syndrome. Finally, molecular and genetic studies are discussed supporting the view that aetiology of steatosis and lipid intra-hepatocytic compartmentation are a major determinant of whether fatty liver is/is not associated with insulin resistance and metabolic syndrome. Data support the novel paradigm of nonalcoholic fatty liver disease as a strong determinant for the development of the metabolic syndrome, which has potentially relevant clinical implications for diagnosing, preventing and treating metabolic syndrome.

  8. Lactate dehydrogenase-elevating virus

    USDA-ARS?s Scientific Manuscript database

    This book chapter describes the taxonomic classification of Lactate dehydrogenase-elevating virus (LDV). Included are: host, genome, classification, morphology, physicochemical and physical properties, nucleic acid, proteins, lipids, carbohydrates, geographic range, phylogenetic properties, biologic...

  9. 21 CFR 73.165 - Ferrous lactate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Ferrous lactate. 73.165 Section 73.165 Food and... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.165 Ferrous lactate. (a) Identity. The color additive ferrous lactate is the ferrous lactate defined in § 184.1311 of this chapter. (b) Specifications. Ferrous...

  10. 21 CFR 73.165 - Ferrous lactate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Ferrous lactate. 73.165 Section 73.165 Food and... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.165 Ferrous lactate. (a) Identity. The color additive ferrous lactate is the ferrous lactate defined in § 184.1311 of this chapter. (b) Specifications. Ferrous...

  11. 21 CFR 73.165 - Ferrous lactate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Ferrous lactate. 73.165 Section 73.165 Food and... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.165 Ferrous lactate. (a) Identity. The color additive ferrous lactate is the ferrous lactate defined in § 184.1311 of this chapter. (b) Specifications. Ferrous...

  12. 21 CFR 73.165 - Ferrous lactate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Ferrous lactate. 73.165 Section 73.165 Food and... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.165 Ferrous lactate. (a) Identity. The color additive ferrous lactate is the ferrous lactate defined in § 184.1311 of this chapter. (b) Specifications. Ferrous...

  13. 21 CFR 73.165 - Ferrous lactate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Ferrous lactate. 73.165 Section 73.165 Food and... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.165 Ferrous lactate. (a) Identity. The color additive ferrous lactate is the ferrous lactate defined in § 184.1311 of this chapter. (b) Specifications. Ferrous...

  14. Grape seed procyanidins administered at physiological doses to rats during pregnancy and lactation promote lipid oxidation and up-regulate AMPK in the muscle of male offspring in adulthood.

    PubMed

    Crescenti, Anna; del Bas, Josep Maria; Arola-Arnal, Anna; Oms-Oliu, Gemma; Arola, Lluís; Caimari, Antoni

    2015-09-01

    The aim of the present study was to test whether the administration of a grape seed procyanidin extract (GSPE) during pregnancy and lactation, at doses extrapolated to human consumption, programs male offspring toward improved metabolism in adulthood. For this purpose, female rats were fed a normal-fat diet (NFD) and treated with either GSPE (25 mg kg(-1) of body weight/day) or vehicle during gestation and lactation. The metabolic programming effects of GSPE were evaluated in the male offspring fed NFD from 30 to 170 days of life. No changes were observed in body weight, adiposity, circulating lipid profile and insulin sensitivity between the offspring of dams treated with GSPE (STD-GSPE group) and their counterparts (STD-veh). However, the STD-GSPE offspring had lower circulating levels of C-reactive protein and lower respiratory quotient values, shifting whole-body energy catabolism from carbohydrate to fat oxidation. Furthermore, the STD-GSPE animals also exhibited increased levels of total and phosphorylated AMP-activated protein kinase (AMPK) and an over-expression of the mRNA levels of key genes related to fatty acid uptake (Fatp1 and CD36) and β-oxidation (pparα and had) in skeletal muscle. Our results indicate that GSPE programs healthy male offspring towards a better circulating inflammatory profile and greater lipid utilisation in adulthood. The metabolic programming effects of GSPE that are related to the enhancement of fatty acid oxidation in skeletal muscle seem to be mediated, at least in part, by AMPK. These findings could be of relevance in the prevention of pathologies associated to lifestyle and aging, such as obesity and insulin resistance.

  15. Lactating Adenoma of the Breast.

    PubMed

    Barco Nebreda, Israel; Vidal, M Carmen; Fraile, Manel; Canales, Lydia; González, Clarisa; Giménez, Nuria; García-Fernández, Antonio

    2016-08-01

    Lactating adenoma is an uncommon breast palpable lesion occurring in pregnancy or lactation. Although it is a benign condition, it often requires core biopsy or even surgery to exclude malignancy. As with other solid lesions in pregnancy and lactation, lactating adenoma needs an accurate evaluation in order to ensure its benign nature. Work-up must include both imaging and histologic findings. Ultrasound evaluation remains the first step in assessing the features of the lesion. Some authors consider magnetic resonance imaging as a useful tool in cases of inconclusive evaluation after ultrasound and histologic exam in an attempt to avoid surgery. Most lactating adenomas resolve spontaneously, whereas others persist or even increase in size and must be removed. The authors present a case of a 35-year-old woman at 6 months postpartum with a lactating adenoma in her right breast. After surgical removal, breastfeeding was perfectly continued within the next 24 hours, which highlights the fact that breast surgery is most often compatible with breastfeeding. © The Author(s) 2016.

  16. Recommendations for Diagnosis, Referral for Liver Biopsy, and Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis.

    PubMed

    Spengler, Erin K; Loomba, Rohit

    2015-09-01

    Nonalcoholic fatty liver disease (NAFLD) is the primary cause of chronic liver disease in the United States, afflicting an estimated 80 to 100 million Americans. Nonalcoholic fatty liver disease is a spectrum of liver diseases composed of nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH). Although nonalcoholic fatty liver has a negligible risk of progression, patients with NASH often develop cirrhosis or hepatocellular carcinoma. Although liver biopsy is required to diagnose NASH, only patients with a high risk of NASH or advanced fibrosis require this evaluation. Despite the high prevalence of NAFLD, well-defined screening recommendations are currently lacking. In this review, suggestions for screening, diagnosis, and initial work-up of NAFLD are given on the basis of established guidelines and recent publications. Proposed drug treatments of NASH are also discussed, highlighting the study outcomes, as well as proposed uses and limitations of these drugs. The literature was searched in PubMed using search terms nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, with filters of "English language." A date range of January 1, 2000, to May 1, 2015, was used for the search. The bibliographies of key references were also searched manually, and seminal publications before the year 2000 were included.

  17. Pediatric Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Bush, Haley; Golabi, Pegah; Younossi, Zobair M.

    2017-01-01

    With the increase in the prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) has become among the leading causes of chronic liver disease in the pediatric age group. Once believed to be a “two-hit process”, it is now clear that the actual pathophysiology of NAFLD is complex and involves multiple pathways. Moreover, NAFLD is not always benign, and patients with non-alcoholic steatohepatitis (NASH) are at increased risk of developing advanced stages of liver disease. It has also been shown that NAFLD is not only a liver disease, but is also associated with multiple extrahepatic manifestations, including cardiovascular diseases, type 2 diabetes, and low bone mineral density. Although the data is scarce in the pediatric population, some studies have suggested that long-term mortality and the requirement of liver transplantation will continue to increase in patients with NAFLD. More studies are needed to better understand the natural history of NAFLD, especially in the pediatric age group. PMID:28598410

  18. Predictors of nonalcoholic steatohepatitis in obese children.

    PubMed

    Lerret, Stacee Marie; Garcia-Rodriguez, Laura; Skelton, Joseph; Biank, Vincent; Kilway, Denise; Telega, Grzegorz

    2011-01-01

    As the prevalence of childhood obesity increases, the incidence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) also escalates. This study's purpose was to identify the clinical criteria to aid in determining when a liver biopsy is indicated for this growing population because currently no guidelines exist. We performed a retrospective chart review on all patients who were seen in the Nutrition Exercise and Weight Loss Kids™ Program at the Children's Hospital of Wisconsin from July 2003 through December 2004. We analyzed only individuals who underwent liver biopsy with the following criteria: (1) no evidence of other liver disease and (2) aspartate transaminase or alanine aminotransferase greater than 200 IU/L or any elevation of or for more than 6 months. Of the 284 patients reviewed, only eight patients (3%) met the criteria for analysis. Biopsy results demonstrated that 100% had histological evidence of NASH with steatosis, and seven of the eight (87.5%) had NASH with fibrosis, cirrhosis, or both. Obese children with an aspartate transaminase or alanine aminotransferase greater than 200 IU/L or any elevation of aspartate transaminase or alanine aminotransferase for more than 6 months, have a strong likelihood of having NASH with or without fibrosis, cirrhosis, or both.

  19. Nonalcoholic Steatohepatitis and Endpoints in Clinical Trials

    PubMed Central

    Hannah, William N.; Torres, Dawn M.

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease in developed countries, and the rates of NAFLD continue to rise in conjunction with the obesity pandemic. While the majority of patients with isolated steatosis generally have a benign course, a diagnosis of nonalcoholic steatohepatitis (NASH) carries a significantly higher risk for progression of disease, cirrhosis, and death. Pharmacologic therapeutic interventions in NASH have largely proven to be ineffective or unappealing due to long-term side-effect profiles, and the majority of patients cannot achieve or sustain targeted weight loss goals, necessitating an urgent need for therapeutic trials and drug development. The complex molecular mechanisms leading to NASH and the long duration of time to develop complications of disease are challenges to developing meaningful clinical endpoints. Because of these challenges, surrogate endpoints that are linked to all-cause mortality, liver-related death, and complications of cirrhosis are much more likely to be beneficial in the majority of patients. PMID:28035202

  20. Nonmedicinal interventions in nonalcoholic fatty liver disease

    PubMed Central

    Neuman, Manuela G; Nanau, Radu M; Cohen, Lawrence B

    2015-01-01

    Unhealthy diet and lack of physical exercise are responsible for fat accumulation in the liver, which may lead to liver disease. Histologically, the severity of the disease has two stages: nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). NAFLD is defined by the presence of steatosis with no evidence of cellular injury such as hepatocyte ballooning. NASH is a distinct entity from NAFLD, and is characterized by the presence of inflammation with hepatocytes damage, with or without fibrosis. While several therapeutic strategies have been proposed to improve this condition, the present review aims to discuss nonmedicinal interventions used to reduce liver involvement or to prevent the disease altogether. The authors investigated dietary patterns and vitamin deficiencies associated with NAFLD, and their role in enhancing disease severity. Additionally, they reviewed the role of exercise and the use of interventions, such as as intragastric balloon and bariatric surgery, for improving disease progression. The authors propose monitoring disease progression or repair by following changes in cytoadipokine levels. PMID:26076224

  1. Nonalcoholic Steatohepatitis: Clinical Presentation, Diagnosis, and Treatment

    PubMed Central

    Stengel, Joel Z.; Harrison, Stephen A.

    2006-01-01

    Nonalcoholic fatty liver disease (NAFLD) is reaching epidemic proportions in our society and is the most common etiology for patients presenting with elevated liver enzymes. Given the significant numbers of patients presenting with NAFLD, it is important to distinguish between simple fatty liver and nonalcoholic steatohepatitis (NASH). Whereas simple fatty liver is thought to have a benign prognosis generally, NASH may progress to cirrhosis in a subset of patients. Performance of liver biopsies in all NAFLD patients is not feasible but recent studies have identified several clinical factors that may predict the patients at greatest risk for NASH and advanced fibrosis, and thus biopsy procedures may be confined to the patients meeting these criteria. Treatment remains focused on improving the underlying insulin resistance that is invariably present in the majority of patients. Diet and exercise remain the cornerstone of therapy, but insulin-sensitizing medication and other agents aimed at reducing oxidative stress or fibrosis may be considered as further studies demonstrating efficacy become available. PMID:28316519

  2. A Case of Chronic Calcific Nonalcoholic Pancreatitis

    PubMed Central

    Kangas-Dick, Aaron; Khan, Umair; Awoniyi, Oluwafunbi; Waqar, Shanza; Tun, Nu Nwe; Wong, Cynthia

    2016-01-01

    Tropical Calcific Pancreatitis (TCP) is a type of chronic calcific nonalcoholic pancreatitis. Similar to nonalcoholic chronic pancreatitis, it presents in the second and third decades of life; however this type is reported mostly in the developing tropical and subtropical countries. It is associated with the formation of pancreatic calculi and a high probability of developing insulin-dependent diabetes mellitus. Epidemiologic studies have shown that these patients have an increased risk of developing pancreatic carcinoma. The etiology of TCP remains uncertain, with the current consensus suggesting genetics as well as possible toxicity from consuming large amounts of cassava, a tuber. Definite diagnosis of TCP requires younger age of onset, history of malnutrition, and presence of diabetes mellitus along with extensive pancreatic calcification and ductal calculi. When patients meet most but not all of these conditions the term Idiopathic Chronic Pancreatitis (ICP) is used. This is a case of a 44-year-old man who presented with most features seen in TCP, and however, was diagnosed with ICP. PMID:27957355

  3. Glucocorticoids and non-alcoholic fatty liver disease.

    PubMed

    Woods, Conor P; Hazlehurst, Jonathon M; Tomlinson, Jeremy W

    2015-11-01

    Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the global obesity and metabolic disease epidemic and is rapidly becoming the leading cause of liver cirrhosis and indication for liver transplantation worldwide. The hallmark pathological finding in NAFLD is excess lipid accumulation within hepatocytes, but it is a spectrum of disease ranging from benign hepatic steatosis to steatohepatitis through to fibrosis, cirrhosis and risk of hepatocellular carcinoma. The exact pathophysiology remains unclear with a multi-hit hypothesis generally accepted as being required for inflammation and fibrosis to develop after initial steatosis. Glucocorticoids have been implicated in the pathogenesis of NAFLD across all stages. They have a diverse array of metabolic functions that have the potential to drive NAFLD acting on both liver and adipose tissue. In the fasting state, they are able to mobilize lipid, increasing fatty acid delivery and in the fed state can promote lipid accumulation. Their action is controlled at multiple levels and in this review will outline the evidence base for the role of GCs in the pathogenesis of NAFLD from cell systems, rodent models and clinical studies and describe interventional strategies that have been employed to modulate glucocorticoid action as a potential therapeutic strategy.

  4. Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis in the United States and the Rest of the World.

    PubMed

    Sayiner, Mehmet; Koenig, Aaron; Henry, Linda; Younossi, Zobair M

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease with increasing prevalence, which can progress to cirrhosis and liver failure. Because of the obesity epidemic and increasing prevalence of metabolic syndrome, NAFLD and its progressive form, nonalcoholic steatohepatitis, are seen more commonly in different parts of the world. This article reviews the worldwide epidemiology of NAFLD and nonalcoholic steatohepatitis. The PubMed database was used to identify studies related to epidemiology of NAFLD in the adult population. It is estimated that the epidemic of obesity will continue to fuel the burden of NAFLD and its long-term complications.

  5. Immunological and molecular basis of nonalcoholic steatohepatitis and nonalcoholic fatty liver disease.

    PubMed

    Radwan, Mohamed M; Radwan, Basil M; Nandipati, Kalyana C; Hunter, William J; Agrawal, Devendra K

    2013-08-01

    The prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is rising worldwide with the increasing incidence of obesity, Type 2 diabetes mellitus and metabolic syndrome. NASH is currently one of the most common indications of liver transplantation in the United States. The immune system plays a major role in the pathogenesis of NAFLD/NASH. The metabolic changes, associated with obesity and metabolic syndrome, induce immunological responses resulting in NAFLD and further aggravation of the metabolic derangement in a feed-forward loop. Genetic and endocrine factors modulate the immunological and metabolic responses and determine the pathophysiological features of NAFLD. Histologically, NAFLD is a spectrum that ranges from simple hepatic steatosis to severe steatohepatitis, liver cirrhosis and/or hepatocellular carcinoma. Liver cirrhosis and hepatocellular carcinoma are responsible for the morbidity and mortality of the disease. This article is a critical evaluation of our current knowledge of the immunological and molecular basis of the disease.

  6. Lactate, a Neglected Factor for Diabetes and Cancer Interaction.

    PubMed

    Wu, Yong; Dong, Yunzhou; Atefi, Mohammad; Liu, Yanjun; Elshimali, Yahya; Vadgama, Jaydutt V

    2016-01-01

    Increasing body of evidence suggests that there exists a connection between diabetes and cancer. Nevertheless, to date, the potential reasons for this association are still poorly understood and currently there is no clinical evidence available to direct the proper management of patients presenting with these two diseases concomitantly. Both cancer and diabetes have been associated with abnormal lactate metabolism and high level of lactate production is the key biological property of these diseases. Conversely, high lactate contribute to a higher insulin resistant status and a more malignant phenotype of cancer cells, promoting diabetes and cancer development and progression. In view of associations between diabetes and cancers, the role of high lactate production in diabetes and cancer interaction should not be neglected. Here, we review the available evidence of lactate's role in different biological characteristics of diabetes and cancer and interactive relationship between them. Understanding the molecular mechanisms behind metabolic remodeling of diabetes- and cancer-related signaling would endow novel preventive and therapeutic approaches for diabetes and cancer treatment.

  7. Lactate, a Neglected Factor for Diabetes and Cancer Interaction

    PubMed Central

    Atefi, Mohammad; Liu, Yanjun; Elshimali, Yahya; Vadgama, Jaydutt V.

    2016-01-01

    Increasing body of evidence suggests that there exists a connection between diabetes and cancer. Nevertheless, to date, the potential reasons for this association are still poorly understood and currently there is no clinical evidence available to direct the proper management of patients presenting with these two diseases concomitantly. Both cancer and diabetes have been associated with abnormal lactate metabolism and high level of lactate production is the key biological property of these diseases. Conversely, high lactate contribute to a higher insulin resistant status and a more malignant phenotype of cancer cells, promoting diabetes and cancer development and progression. In view of associations between diabetes and cancers, the role of high lactate production in diabetes and cancer interaction should not be neglected. Here, we review the available evidence of lactate's role in different biological characteristics of diabetes and cancer and interactive relationship between them. Understanding the molecular mechanisms behind metabolic remodeling of diabetes- and cancer-related signaling would endow novel preventive and therapeutic approaches for diabetes and cancer treatment. PMID:28077918

  8. Nutritional aspects of human lactation*

    PubMed Central

    Thomson, A. M.; Black, A. E.

    1975-01-01

    This paper reviews the literature on the incidence and duration of breast-feeding in various countries, the volume and composition of breast milk, the health and nutrition of breast-fed babies as judged by growth and morbidity, maternal nutritional requirements during lactation, and the effect of prolonged lactation on maternal health. It appears that lactation can be as well sustained by impoverished as by affluent mothers, and that even in communities where malnutrition is common the average growth of infants is satisfactory up to the age of about 3 months on a diet of breast milk alone. Breast milk appears to have specific anti-infective properties, but prolonged breast-feeding will not prevent infections among older infants reared in a poor environment. The authors believe that breast-feeding is the best form of nutrition for the young infant and deplore its decline in modern industrial societies. The recommendations of various FAO/WHO Expert Groups on nutritional intakes during lactation are summarized. The need for an increased daily energy intake of 4.2 MJ (1 000 kcal) is questioned, and an increase of 2.5 MJ (600 kcal) is suggested. Data on the effect of prolonged lactation on the health of the mother are scanty; body weight appears to be maintained even among poorly nourished mothers. The authors stress the need for well-planned and technically adequate studies of the material and psychological factors involved in breast feeding. PMID:816479

  9. Micro RNAs in the development of non-alcoholic fatty liver disease.

    PubMed

    Gerhard, Glenn S; DiStefano, Johanna K

    2015-02-27

    Nonalcoholic fatty liver disease or nonalcoholic fatty liver disease (NAFLD) refers to a group of disorders that arise from the accrual of fat in hepatocytes. Although various factors have been associated with the development of NAFLD, including genetic predisposition and environmental exposures, little is known about the underlying pathogenesis of the disease. Research efforts are ongoing to identify biological targets and signaling pathways that mediate NAFLD. Emerging evidence has implicated a role for micro RNAs (miRNAs), short single-stranded molecules that regulate gene expression either transcriptionally, through targeting of promoter regions, or post-transcriptionally, by blocking translation or promoting cleavage of specific target mRNAs. Several miRNAs have been associated with NAFLD, although our understanding of the biology underlying their role is still emerging. The goal of this review is to present an overview of the current state of knowledge of miRNAs involved in the development of NAFLD across a range of in vitro and in vivo models, including miRNAs that contribute to pathological mechanisms related to fatty liver in humans. Much less is known about the specific targets of miRNAs in cells, nor the molecular mechanisms involved in the development and progression NAFLD and related outcomes. More recently, the identification and validation of miRNA signatures in serum may facilitate the development of improved methods for diagnosis and clinical monitoring of disease progression.

  10. Micro RNAs in the development of non-alcoholic fatty liver disease

    PubMed Central

    Gerhard, Glenn S; DiStefano, Johanna K

    2015-01-01

    Nonalcoholic fatty liver disease or nonalcoholic fatty liver disease (NAFLD) refers to a group of disorders that arise from the accrual of fat in hepatocytes. Although various factors have been associated with the development of NAFLD, including genetic predisposition and environmental exposures, little is known about the underlying pathogenesis of the disease. Research efforts are ongoing to identify biological targets and signaling pathways that mediate NAFLD. Emerging evidence has implicated a role for micro RNAs (miRNAs), short single-stranded molecules that regulate gene expression either transcriptionally, through targeting of promoter regions, or post-transcriptionally, by blocking translation or promoting cleavage of specific target mRNAs. Several miRNAs have been associated with NAFLD, although our understanding of the biology underlying their role is still emerging. The goal of this review is to present an overview of the current state of knowledge of miRNAs involved in the development of NAFLD across a range of in vitro and in vivo models, including miRNAs that contribute to pathological mechanisms related to fatty liver in humans. Much less is known about the specific targets of miRNAs in cells, nor the molecular mechanisms involved in the development and progression NAFLD and related outcomes. More recently, the identification and validation of miRNA signatures in serum may facilitate the development of improved methods for diagnosis and clinical monitoring of disease progression. PMID:25729477

  11. Highly efficient L-lactate production using engineered Escherichia coli with dissimilar temperature optima for L-lactate formation and cell growth

    PubMed Central

    2014-01-01

    L-Lactic acid, one of the most important chiral molecules and organic acids, is produced via pyruvate from carbohydrates in diverse microorganisms catalyzed by an NAD+-dependent L-lactate dehydrogenase. Naturally, Escherichia coli does not produce L-lactate in noticeable amounts, but can catabolize it via a dehydrogenation reaction mediated by an FMN-dependent L-lactate dehydrogenase. In aims to make the E. coli strain to produce L-lactate, three L-lactate dehydrogenase genes from different bacteria were cloned and expressed. The L-lactate producing strains, 090B1 (B0013-070, ΔldhA::diflldD::Pldh-ldhLca), 090B2 (B0013-070, ΔldhA::diflldD::Pldh-ldhStrb) and 090B3 (B0013-070, ΔldhA::diflldD::Pldh-ldhBcoa) were developed from a previously developed D-lactate over-producing strain, E. coli strain B0013-070 (ack-ptappspflBdldpoxBadhEfrdA) by: (1) deleting ldhA to block D-lactate formation, (2) deleting lldD to block the conversion of L-lactate to pyruvate, and (3) expressing an L-lactate dehydrogenase (L-LDH) to convert pyruvate to L-lactate under the control of the ldhA promoter. Fermentation tests were carried out in a shaking flask and in a 25-l bioreactor. Strains 090B1, 090B2 or 090B3 were shown to metabolize glucose to L-lactate instead of D-lactate. However, L-lactate yield and cell growth rates were significantly different among the metabolically engineered strains which can be attributed to a variation between temperature optimum for cell growth and temperature optimum for enzymatic activity of individual L-LDH. In a temperature-shifting fermentation process (cells grown at 37°C and L-lactate formed at 42°C), E. coli 090B3 was able to produce 142.2 g/l of L-lactate with no more than 1.2 g/l of by-products (mainly acetate, pyruvate and succinate) accumulated. In conclusion, the production of lactate by E. coli is limited by the competition relationship between cell growth and lactate synthesis. Enzymatic properties, especially the thermodynamics of an L

  12. Accumulation of NKT cells in Progressive Nonalcoholic Fatty Liver Disease

    PubMed Central

    Syn, Wing-Kin; Oo, Ye Htun; Pereira, Thiago A; Karaca, Gamze F; Jung, Youngmi; Omenetti, Alessia; Witek, Rafal P; Choi, Steve S; Guy, Cynthia D; Fearing, Caitlin M; Teaberry, Vanessa; Pereira, Fausto E L; Adams, David H; Diehl, Anna Mae

    2010-01-01

    Liver inflammation is greater in nonalcoholic steatohepatitis (NASH) than steatosis, suggesting that immune responses contribute to NAFLD progression. Livers normally contain many natural killer T (NKT) cells which produce factors that modulate inflammatory and fibrogenic responses. Such cells are relatively depleted in steatosis, but their status in more advanced NAFLD is uncertain. We hypothesized that NKT cells accumulate and promote fibrosis progression in NASH. We aimed to determine if livers become enriched with NKT cells during NASH-related fibrosis; identify responsible mechanisms; and assess if NKT cells stimulate fibrogenesis. NKT cells were analyzed in wild type mice and Ptc+/-mice with an overly-active Hedgehog (Hh) pathway, before and after feeding methionine choline deficient (MCD) diets to induce NASH-related fibrosis; effects of NKT cell-derived factors on hepatic stellate cells (HSC) were examined and fibrogenesis was evaluated in CD1d-deficient mice which lack NKT cells; NKT cells were quantified in human cirrhotic and non-diseased livers. During NASH-related fibrogenesis in wild-type mice, Hh pathway activation occurred, leading to induction of factors that promoted NKT cell recruitment, retention and viability, plus liver enrichment with NKT cells. Ptc+/- mice accumulated more NKT cells and developed worse liver fibrosis; CD1d-deficient mice which lack NKT cells were protected from fibrosis. NKT cell-conditioned medium stimulated HSC to become myofibroblastic. Liver explants were 2-fold enriched with NKT cells in patients with non-NASH cirrhosis, and 4-fold enriched in patients with NASH-cirrhosis. In conclusion, Hh pathway activation leads to hepatic enrichment with NKT cells that contribute to fibrosis progression in NASH. PMID:20512988

  13. Sales impact of displaying alcoholic and non-alcoholic beverages in end-of-aisle locations: an observational study.

    PubMed

    Nakamura, Ryota; Pechey, Rachel; Suhrcke, Marc; Jebb, Susan A; Marteau, Theresa M

    2014-05-01

    In-store product placement is perceived to be a factor underpinning impulsive food purchasing but empirical evidence is limited. In this study we present the first in-depth estimate of the effect of end-of-aisle display on sales, focussing on alcohol. Data on store layout and product-level sales during 2010-11 were obtained for one UK grocery store, comprising detailed information on shelf space, price, price promotion and weekly sales volume in three alcohol categories (beer, wine, spirits) and three non-alcohol categories (carbonated drinks, coffee, tea). Multiple regression techniques were used to estimate the effect of end-of-aisle display on sales, controlling for price, price promotion, and the number of display locations for each product. End-of-aisle display increased sales volumes in all three alcohol categories: by 23.2% (p = 0.005) for beer, 33.6% (p < 0.001) for wine, and 46.1% (p < 0.001) for spirits, and for three non-alcohol beverage categories: by 51.7% (p < 0.001) for carbonated drinks, 73.5% (p < 0.001) for coffee, and 113.8% (p < 0.001) for tea. The effect size was equivalent to a decrease in price of between 4% and 9% per volume for alcohol categories, and a decrease in price of between 22% and 62% per volume for non-alcohol categories. End-of-aisle displays appear to have a large impact on sales of alcohol and non-alcoholic beverages. Restricting the use of aisle ends for alcohol and other less healthy products might be a promising option to encourage healthier in-store purchases, without affecting availability or cost of products.

  14. Sales impact of displaying alcoholic and non-alcoholic beverages in end-of-aisle locations: An observational study

    PubMed Central

    Nakamura, Ryota; Pechey, Rachel; Suhrcke, Marc; Jebb, Susan A.; Marteau, Theresa M.

    2014-01-01

    In-store product placement is perceived to be a factor underpinning impulsive food purchasing but empirical evidence is limited. In this study we present the first in-depth estimate of the effect of end-of-aisle display on sales, focussing on alcohol. Data on store layout and product-level sales during 2010–11 were obtained for one UK grocery store, comprising detailed information on shelf space, price, price promotion and weekly sales volume in three alcohol categories (beer, wine, spirits) and three non-alcohol categories (carbonated drinks, coffee, tea). Multiple regression techniques were used to estimate the effect of end-of-aisle display on sales, controlling for price, price promotion, and the number of display locations for each product. End-of-aisle display increased sales volumes in all three alcohol categories: by 23.2% (p = 0.005) for beer, 33.6% (p < 0.001) for wine, and 46.1% (p < 0.001) for spirits, and for three non-alcohol beverage categories: by 51.7% (p < 0.001) for carbonated drinks, 73.5% (p < 0.001) for coffee, and 113.8% (p < 0.001) for tea. The effect size was equivalent to a decrease in price of between 4% and 9% per volume for alcohol categories, and a decrease in price of between 22% and 62% per volume for non-alcohol categories. End-of-aisle displays appear to have a large impact on sales of alcohol and non-alcoholic beverages. Restricting the use of aisle ends for alcohol and other less healthy products might be a promising option to encourage healthier in-store purchases, without affecting availability or cost of products. PMID:24632050

  15. Herbal medicines and nonalcoholic fatty liver disease.

    PubMed

    Yao, Hong; Qiao, Yu-Jie; Zhao, Ya-Li; Tao, Xu-Feng; Xu, Li-Na; Yin, Lian-Hong; Qi, Yan; Peng, Jin-Yong

    2016-08-14

    Nonalcoholic fatty liver disease (NAFLD), which is characterized by excessive fat accumulation in the liver of patients who consume little or no alcohol, becomes increasingly common with rapid economic development. Long-term excess fat accumulation leads to NAFLD and represents a global health problem with no effective therapeutic approach. NAFLD is considered to be a series of complex, multifaceted pathological processes involving oxidative stress, inflammation, apoptosis, and metabolism. Over the past decades, herbal medicines have garnered growing attention as potential therapeutic agents to prevent and treat NAFLD, due to their high efficacy and low risk of side effects. In this review, we evaluate the use of herbal medicines (including traditional Chinese herbal formulas, crude extracts from medicinal plants, and pure natural products) to treat NAFLD. These herbal medicines are natural resources that can inform innovative drug research and the development of treatments for NAFLD in the future.

  16. Death expectancies in alcoholic and nonalcoholic persons.

    PubMed

    Lowe, W C; Thomas, S D

    1977-10-01

    The Do-It-Yourself Death Certificate (DIYDC) was administered to a group of alcoholic inpatients (N = 39) and to a group of university employees (N = 39). The groups were matched on age, sex, and race. Both alcoholics and nonalcoholics projected unrealistic expectations about their deaths when compared with actuarial cause of death data, but this was somewhat more true of those in the alcoholic group, who expected to live longer than would be expected and who only infrequently attributed their deaths to drinking. Strong preferences were expressed for a quick death, and some differences were observed between the groups with regard to seasonal expectations of time of death and attitudes toward life-prolonging techniques. The DIYDC appears to be a useful adjunct to existing methods of death research, and it may have practical applications with some clinical groups, provided that certain ethical considerations are observed.

  17. Lipoprotein metabolism in nonalcoholic fatty liver disease

    PubMed Central

    Jiang, Zhenghui Gordon; Robson, Simon C.; Yao, Zemin

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD), an escalating health problem worldwide, covers a spectrum of pathologies characterized by fatty accumulation in hepatocytes in early stages, with potential progression to liver inflammation, fibrosis, and failure. A close, yet poorly understood link exists between NAFLD and dyslipidemia, a constellation of abnormalities in plasma lipoproteins including triglyceride-rich very low density lipoproteins. Apolipoproteins are a group of primarily liver-derived proteins found in serum lipoproteins; they not only play an extracellular role in lipid transport between vital organs through circulation, but also play an important intracellular role in hepatic lipoprotein assembly and secretion. The liver functions as the central hub for lipoprotein metabolism, as it dictates lipoprotein production and to a significant extent modulates lipoprotein clearance. Lipoprotein metabolism is an integral component of hepatocellular lipid homeostasis and is implicated in the pathogenesis, potential diagnosis, and treatment of NAFLD. PMID:23554788

  18. Thyroid dysfunction and nonalcoholic fatty liver disease.

    PubMed

    Efstathiadou, Zoe A; Kita, Marina D; Polyzos, Stergios A

    2017-02-09

    Thyroid hormones are crucial for hepatic lipid and glucose metabolism. Nonalcoholic fatty liver disease (NAFLD), a very common and potentially serious disease of modern society, shares common clinical features with hypothyroidism, such as obesity, insulin resistance and dyslipidemia. Furthermore, in certain studies, increased prevalence of hypothyroidism was observed in patients with NAFLD. However, whether there is a linear relationship between thyroid hormone levels and NAFLD incidence and severity, including values within or in proximity to the reference range remains a contradictory subject in the literature. On the other hand, attempts to treat NAFLD with thyromimetic drugs remain at an early stage. In this review, data derived from observational studies along with evidence on possible treatment with thyroid hormone analogues are presented.

  19. Extrahepatic Manifestations of Nonalcoholic Fatty Liver Disease.

    PubMed

    VanWagner, Lisa B; Rinella, Mary E

    2016-06-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide with an increased prevalence of metabolic, macro- and microvascular complications. The primary causes of mortality in NAFLD are cardiovascular disease (CVD), malignancy and liver disease. NAFLD is a multisystem disease that affects a variety of extra-hepatic organ systems. The main focus of this review is to summarize the reported extra-hepatic associations, which include CVD, chronic kidney disease, obstructive sleep apnea, osteoporosis, psoriasis, colorectal cancer, iron overload and various endocrinopathies (e.g. type 2 diabetes mellitus, thyroid dysfunction, and polycystic ovarian syndrome). Due to the systemic manifestations of NAFLD patients require a multidisciplinary assessment and may benefit from more rigorous surveillance and early treatment interventions to decrease mortality related to malignancy or cardiometabolic diseases.

  20. Herbal medicines and nonalcoholic fatty liver disease

    PubMed Central

    Yao, Hong; Qiao, Yu-Jie; Zhao, Ya-Li; Tao, Xu-Feng; Xu, Li-Na; Yin, Lian-Hong; Qi, Yan; Peng, Jin-Yong

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), which is characterized by excessive fat accumulation in the liver of patients who consume little or no alcohol, becomes increasingly common with rapid economic development. Long-term excess fat accumulation leads to NAFLD and represents a global health problem with no effective therapeutic approach. NAFLD is considered to be a series of complex, multifaceted pathological processes involving oxidative stress, inflammation, apoptosis, and metabolism. Over the past decades, herbal medicines have garnered growing attention as potential therapeutic agents to prevent and treat NAFLD, due to their high efficacy and low risk of side effects. In this review, we evaluate the use of herbal medicines (including traditional Chinese herbal formulas, crude extracts from medicinal plants, and pure natural products) to treat NAFLD. These herbal medicines are natural resources that can inform innovative drug research and the development of treatments for NAFLD in the future. PMID:27570425

  1. Treatment of nonalcoholic fatty liver disease

    PubMed Central

    Siebler, Juergen; Galle, Peter R

    2006-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause for elevated liver enzymes in the developed nations. Beyond prevention programs which are of particular interest because of the increasing number of overweight children, treatment should be focussed on the most important risk factors, obesity and insulin resistance. As a consequence of elucidating the pathomechanisms of NAFLD, the number of potential therapeutic options increased. However, many studies investigating the therapeutic effect show shortcomings in at least one of the following points: lack of a serial liver biopsy, short term of treatment and limited number of included patients. The second generation insulin sensitizer pioglitazone and rosiglitazone show the most promising improvements in NAFLD, but weight gain and potential hepatotoxicity calls for attention. In conclusion, a general recommendation for the application of specific drugs cannot be given. Besides controlled clinical trials, weight reduction and physical activity to improve insulin sensitivity in obese patients should be the priority objective. PMID:16610015

  2. The relationship between oxidative stress and nonalcoholic fatty liver disease: Its effects on the development of nonalcoholic steatohepatitis.

    PubMed

    Ucar, Fatma; Sezer, Sevilay; Erdogan, Serpil; Akyol, Sumeyya; Armutcu, Ferah; Akyol, Omer

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are the most common underlying causes of chronic liver injury. They are associated with a wide spectrum of hepatic disorders including basic steatosis, steatohepatitis, and cirrhosis. The molecular and cellular mechanisms underlying hepatic injury in NAFLD and NASH are still unknown. This review describes the roles of oxidative stress and inflammatory responses in the pathogenesis of NAFLD and its progression to NASH.

  3. Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Ur Rahman, Zia; Hurairah, Abu

    2016-01-01

    Our objective was to study nonalcoholic fatty liver disease (NAFLD) as a relevant risk factor associated with hepatocellular carcinoma (HCC) in patients with and without cirrhosis. HCC is a common cancer worldwide that predominantly involves patients with hepatic cirrhosis. HCC has recently been linked to NAFLD, the hepatic manifestation of obesity and related metabolic disorders. This association is alarming due to the high prevalence of NAFLD globally, which may contribute to the rising incidence of HCC. A 31-year-old female with a history of dyslipidemia, hypertension, and diabetes mellitus presented with abdominal pain that persisted for six months. The pain was associated with gastrointestinal symptoms and weight loss. She was drug-free and a nonalcoholic and a nonsmoker. The physical examination was unremarkable. The abdominal exam showed a soft and non-tender abdomen, with no organomegaly or ascites. The laboratory evaluation was unremarkable. The imaging studies showed a hypodense lesion in the right hepatic lobe with strong arterial enhancement. Subsequently, the patient underwent a liver biopsy. The histopathology results were consistent with HCC. The patient underwent an uneventful segment VI liver resection and tumor-free margins were achieved. In our patient, NAFLD was designated as an independent etiology for HCC, without cirrhosis. Our patient recovered well and has been disease free for over a year. HCC may complicate non-cirrhotic NAFLD with mild or absent fibrosis, greatly expanding the population potentially at higher risk of HCC. These results provide new targets for surveillance, prevention, early recognition, and effective treatment of HCC associated with NAFLD. PMID:27733959

  4. Biomarkers in nonalcoholic fatty liver disease

    PubMed Central

    Neuman, Manuela G; Cohen, Lawrence B; Nanau, Radu M

    2014-01-01

    BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition characterized by insulin resistance, type 2 diabetes and fat accumulation in the liver that may cause hepatic inflammation and progressive scarring leading to nonalcoholic steatohepatitis (NASH) and irreversible liver damage (cirrhosis). As a result, there has been increased recognition of the need to assess and closely monitor individuals for risk factors of components of NAFLD and NASH, as well as the severity of these conditions using biomarkers. AIM: To review the biomarkers used to diagnose and define the severity of NAFLD and NASH. METHODS: A comprehensive PubMed and Google Scholar literature search was performed using the terms “non-alcoholic fatty liver disease”, “non-alcoholic steatohepatitis”, as well as the name of each biomarker known to be used. Articles indexed between 2004 and 2014 were used. Each author read the publications separately and the results were discussed. RESULTS: Biomarkers offer a potential prognostic or diagnostic indicator for disease manifestation, progression or both. Serum biomarkers, including total cholesterol, triglycerides, insulin resistance and C-peptide, have been used for many years. Emerging biomarkers, such as apolipoprotein A1, apolipoprotein B, leptin, adiponectin, free fatty acids, ghrelin and tumour necrosis factor-alpha, have been proposed as tools that could provide valuable complementary information to that obtained from traditional biomarkers. Moreover, markers of cell death and mitochondrial dysfunction (cytokeratins) represent powerful predictors of risk. For biomarkers to be clinically useful in accurately diagnosing and treating disorders, age-specific reference intervals that account for differences in sex and ethnic origin are a necessity. CONCLUSIONS: The present review attempts to provide a comprehensive analysis of the emerging risk biomarkers of NAFLD and NASH, and to use the clinical significance and analytical

  5. Radiologic evaluation of nonalcoholic fatty liver disease

    PubMed Central

    Lee, Seung Soo; Park, Seong Ho

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a frequent cause of chronic liver diseases, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH)-related liver cirrhosis. Although liver biopsy is still the gold standard for the diagnosis of NAFLD, especially for the diagnosis of NASH, imaging methods have been increasingly accepted as noninvasive alternatives to liver biopsy. Ultrasonography is a well-established and cost-effective imaging technique for the diagnosis of hepatic steatosis, especially for screening a large population at risk of NAFLD. Ultrasonography has a reasonable accuracy in detecting moderate-to-severe hepatic steatosis although it is less accurate for detecting mild hepatic steatosis, operator-dependent, and rather qualitative. Computed tomography is not appropriate for general population assessment of hepatic steatosis given its inaccuracy in detecting mild hepatic steatosis and potential radiation hazard. However, computed tomography may be effective in specific clinical situations, such as evaluation of donor candidates for hepatic transplantation. Magnetic resonance spectroscopy and magnetic resonance imaging are now regarded as the most accurate practical methods of measuring liver fat in clinical practice, especially for longitudinal follow-up of patients with NAFLD. Ultrasound elastography and magnetic resonance elastography are increasingly used to evaluate the degree of liver fibrosis in patients with NAFLD and to differentiate NASH from simple steatosis. This article will review current imaging methods used to evaluate hepatic steatosis, including the diagnostic accuracy, limitations, and practical applicability of each method. It will also briefly describe the potential role of elastography techniques in the evaluation of patients with NAFLD. PMID:24966609

  6. Lactate does not activate NF-κB in oxidative tumor cells

    PubMed Central

    Van Hée, Vincent F.; Pérez-Escuredo, Jhudit; Cacace, Andrea; Copetti, Tamara; Sonveaux, Pierre

    2015-01-01

    The lactate anion is currently emerging as an oncometabolite. Lactate, produced and exported by glycolytic and glutaminolytic cells in tumors, can be recycled as an oxidative fuel by oxidative tumors cells. Independently of hypoxia, it can also activate transcription factor hypoxia-inducible factor-1 (HIF-1) in tumor and endothelial cells, promoting angiogenesis. These protumoral activities of lactate depend on lactate uptake, a process primarily facilitated by the inward, passive lactate-proton symporter monocarboxylate transporter 1 (MCT1); the conversion of lactate and NAD+ to pyruvate, NADH and H+ by lactate dehydrogenase-1 (LDH-1); and a competition between pyruvate and α-ketoglutarate that inhibits prolylhydroxylases (PHDs). Endothelial cells do not primarily use lactate as an oxidative fuel but, rather, as a signaling agent. In addition to HIF-1, lactate can indeed activate transcription factor nuclear factor-κB (NF-κB) in these cells, through a mechanism not only depending on PHD inhibition but also on NADH alimenting NAD(P)H oxidases to generate reactive oxygen species (ROS). While NF-κB activity in endothelial cells promotes angiogenesis, NF-κB activation in tumor cells is known to stimulate tumor progression by conferring resistance to apoptosis, stemness, pro-angiogenic and metastatic capabilities. In this study, we therefore tested whether exogenous lactate could activate NF-κB in oxidative tumor cells equipped for lactate signaling. We report that, precisely because they are oxidative, HeLa and SiHa human tumor cells do not activate NF-κB in response to lactate. Indeed, while lactate-derived pyruvate is well-known to inhibit PHDs in these cells, we found that NADH aliments oxidative phosphorylation (OXPHOS) in mitochondria rather than NAD(P)H oxidases in the cytosol. These data were confirmed using oxidative human Cal27 and MCF7 tumor cells. This new information positions the malate-aspartate shuttle as a key player in the oxidative metabolism

  7. Fructose, high fructose corn syrup, sucrose, and non-alcoholic liver disease

    USDA-ARS?s Scientific Manuscript database

    Nonalcoholic fatty liver disease (NAFLD), formerly called nonalcoholic steatohepatitis, is characterized by hepatic steatosis and abnormal triglyceride accumulation in liver cells. Its etiology, pathophysiology, and pathogenesis are still poorly understood. Some have suggested that the increased in...

  8. Genome-scale study reveals reduced metabolic adaptability in patients with non-alcoholic fatty liver disease.

    PubMed

    Hyötyläinen, Tuulia; Jerby, Livnat; Petäjä, Elina M; Mattila, Ismo; Jäntti, Sirkku; Auvinen, Petri; Gastaldelli, Amalia; Yki-Järvinen, Hannele; Ruppin, Eytan; Orešič, Matej

    2016-02-03

    Non-alcoholic fatty liver disease (NAFLD) is a major risk factor leading to chronic liver disease and type 2 diabetes. Here we chart liver metabolic activity and functionality in NAFLD by integrating global transcriptomic data, from human liver biopsies, and metabolic flux data, measured across the human splanchnic vascular bed, within a genome-scale model of human metabolism. We show that an increased amount of liver fat induces mitochondrial metabolism, lipolysis, glyceroneogenesis and a switch from lactate to glycerol as substrate for gluconeogenesis, indicating an intricate balance of exacerbated opposite metabolic processes in glycemic regulation. These changes were associated with reduced metabolic adaptability on a network level in the sense that liver fat accumulation puts increasing demands on the liver to adaptively regulate metabolic responses to maintain basic liver functions. We propose that failure to meet excessive metabolic challenges coupled with reduced metabolic adaptability may lead to a vicious pathogenic cycle leading to the co-morbidities of NAFLD.

  9. Genome-scale study reveals reduced metabolic adaptability in patients with non-alcoholic fatty liver disease

    PubMed Central

    Hyötyläinen, Tuulia; Jerby, Livnat; Petäjä, Elina M.; Mattila, Ismo; Jäntti, Sirkku; Auvinen, Petri; Gastaldelli, Amalia; Yki-Järvinen, Hannele; Ruppin, Eytan; Orešič, Matej

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a major risk factor leading to chronic liver disease and type 2 diabetes. Here we chart liver metabolic activity and functionality in NAFLD by integrating global transcriptomic data, from human liver biopsies, and metabolic flux data, measured across the human splanchnic vascular bed, within a genome-scale model of human metabolism. We show that an increased amount of liver fat induces mitochondrial metabolism, lipolysis, glyceroneogenesis and a switch from lactate to glycerol as substrate for gluconeogenesis, indicating an intricate balance of exacerbated opposite metabolic processes in glycemic regulation. These changes were associated with reduced metabolic adaptability on a network level in the sense that liver fat accumulation puts increasing demands on the liver to adaptively regulate metabolic responses to maintain basic liver functions. We propose that failure to meet excessive metabolic challenges coupled with reduced metabolic adaptability may lead to a vicious pathogenic cycle leading to the co-morbidities of NAFLD. PMID:26839171

  10. Catabolism of Exogenous Lactate Reveals It as a Legitimate Metabolic Substrate in Breast Cancer

    PubMed Central

    Kennedy, Kelly M.; Scarbrough, Peter M.; Ribeiro, Anthony; Richardson, Rachel; Yuan, Hong; Sonveaux, Pierre; Landon, Chelsea D.; Chi, Jen-Tsan; Pizzo, Salvatore

    2013-01-01

    Lactate accumulation in tumors has been associated with metastases and poor overall survival in cancer patients. Lactate promotes angiogenesis and metastasis, providing rationale for understanding how it is processed by cells. The concentration of lactate in tumors is a balance between the amount produced, amount carried away by vasculature and if/how it is catabolized by aerobic tumor or stromal cells. We examined lactate metabolism in human normal and breast tumor cell lines and rat breast cancer: 1. at relevant concentrations, 2. under aerobic vs. hypoxic conditions, 3. under conditions of normo vs. hypoglucosis. We also compared the avidity of tumors for lactate vs. glucose and identified key lactate catabolites to reveal how breast cancer cells process it. Lactate was non-toxic at clinically relevant concentrations. It was taken up and catabolized to alanine and glutamate by all cell lines. Kinetic uptake rates of lactate in vivo surpassed that of glucose in R3230Ac mammary carcinomas. The uptake appeared specific to aerobic tumor regions, consistent with the proposed “metabolic symbiont” model; here lactate produced by hypoxic cells is used by aerobic cells. We investigated whether treatment with alpha-cyano-4-hydroxycinnamate (CHC), a MCT1 inhibitor, would kill cells in the presence of high lactate. Both 0.1 mM and 5 mM CHC prevented lactate uptake in R3230Ac cells at lactate concentrations at ≤20 mM but not at 40 mM. 0.1 mM CHC was well-tolerated by R3230Ac and MCF7 cells, but 5 mM CHC killed both cell lines ± lactate, indicating off-target effects. This study showed that breast cancer cells tolerate and use lactate at clinically relevant concentrations in vitro (± glucose) and in vivo. We provided additional support for the metabolic symbiont model and discovered that breast cells prevailingly take up and catabolize lactate, providing rationale for future studies on manipulation of lactate catabolism pathways for therapy. PMID:24069390

  11. Catabolism of exogenous lactate reveals it as a legitimate metabolic substrate in breast cancer.

    PubMed

    Kennedy, Kelly M; Scarbrough, Peter M; Ribeiro, Anthony; Richardson, Rachel; Yuan, Hong; Sonveaux, Pierre; Landon, Chelsea D; Chi, Jen-Tsan; Pizzo, Salvatore; Schroeder, Thies; Dewhirst, Mark W

    2013-01-01

    Lactate accumulation in tumors has been associated with metastases and poor overall survival in cancer patients. Lactate promotes angiogenesis and metastasis, providing rationale for understanding how it is processed by cells. The concentration of lactate in tumors is a balance between the amount produced, amount carried away by vasculature and if/how it is catabolized by aerobic tumor or stromal cells. We examined lactate metabolism in human normal and breast tumor cell lines and rat breast cancer: 1. at relevant concentrations, 2. under aerobic vs. hypoxic conditions, 3. under conditions of normo vs. hypoglucosis. We also compared the avidity of tumors for lactate vs. glucose and identified key lactate catabolites to reveal how breast cancer cells process it. Lactate was non-toxic at clinically relevant concentrations. It was taken up and catabolized to alanine and glutamate by all cell lines. Kinetic uptake rates of lactate in vivo surpassed that of glucose in R3230Ac mammary carcinomas. The uptake appeared specific to aerobic tumor regions, consistent with the proposed "metabolic symbiont" model; here lactate produced by hypoxic cells is used by aerobic cells. We investigated whether treatment with alpha-cyano-4-hydroxycinnamate (CHC), a MCT1 inhibitor, would kill cells in the presence of high lactate. Both 0.1 mM and 5 mM CHC prevented lactate uptake in R3230Ac cells at lactate concentrations at ≤ 20 mM but not at 40 mM. 0.1 mM CHC was well-tolerated by R3230Ac and MCF7 cells, but 5 mM CHC killed both cell lines ± lactate, indicating off-target effects. This study showed that breast cancer cells tolerate and use lactate at clinically relevant concentrations in vitro (± glucose) and in vivo. We provided additional support for the metabolic symbiont model and discovered that breast cells prevailingly take up and catabolize lactate, providing rationale for future studies on manipulation of lactate catabolism pathways for therapy.

  12. Hepatic Reticuloendothelial System Cell Iron Deposition is Associated with Increased Apoptosis in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Maliken, Bryan D.; Nelson, James E.; Klintworth, Heather M.; Beauchamp, Mary; Yeh, Matthew M.; Kowdley, Kris V.

    2013-01-01

    The goal of this study was to examine the relationship between presence of hepatic iron deposition, apoptosis, histologic features and serum markers of oxidative stress and cell death in nonalcoholic fatty liver disease. Clinical, biochemical, metabolic and independent histopathologic assessment was conducted in 83 unselected patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD)from a single center. Apoptosis and necrosis in serum was quantified using serum cytokeratin-18(CK18) M30 and M65ELISAsand in liver by TUNEL stainingin situ. Serum malondialdehyde(MDA) and thioredoxin-1 (Trx-1) levels were measured to evaluate oxidative stress. Presence of reticuloendothelial system cell (RES) iron in the liver was associated with nonalcoholic steatohepatitis (p<0.05) and increased hepatic TUNEL staining (p=0.02),as well as increased serum levels of apoptosis-specific (M30, p=0.013) and total (M65, p=0.006) CK-18 fragments, higher MDA (p=0.002) and lower antioxidant Trx-1 levels (p=0.012) compared to patients without stainable hepatic iron. NAFLD patients with a hepatocellular iron staining pattern also had increased serum MDA (p=0.006) but not M30 CK-18 levels or TUNEL staining compared to subjects without stainable hepatic iron. Patients with iron deposition limited to hepatocytes had a lower proportion of apoptosis-specific M30 fragments relative to total M65 CK-18 levels (37% vs. ≤ 25%, p<0.05). Conclusions Presence of iron in liver RES cells is associated with NASH, increased apoptosis and increased oxidative stress. Hepatocellular iron deposition in NAFLD is also associated with oxidative stress and may promote hepatocyte necrosis in this disease. PMID:23325576

  13. Short communication: Early-lactation, but not mid-lactation, bovine lactoferrin preparation increases epithelial barrier integrity of Caco-2 cell layers.

    PubMed

    Anderson, Rachel C; Bassett, Shalome A; Haggarty, Neill W; Gopal, Pramod K; Armstrong, Kelly M; Roy, Nicole C

    2017-02-01

    Bovine lactoferrin is an important milk protein with many health-promoting properties, including improving intestinal barrier integrity. Dysfunction of this barrier, commonly referred to as "leaky gut," has been linked to inflammatory and autoimmune diseases. With some processing techniques, lactoferrin isolated from milk collected at the start of the milking season (early lactation) may have lower purity than that isolated from milk collected during the rest of the milking season (mid-lactation) and could result in differences in bioactivity based on the stage of lactation. We compared reversed-phase HPLC chromatographs of early-lactation and mid-lactation preparations and found that both had large chromatograph peaks at the time predicted for lactoferrin. The notable difference between the 2 chromatographs was a much larger peak in the early-lactation lactoferrin sample that was determined to be angiogenin. Angiogenin was first identified due to its ability to induce new blood vessel formation, but is now known to be involved in numerous physiological processes. Then, we compared the effects of early-lactation and mid-lactation lactoferrin preparations in 2 bioassays: trans-epithelial electrical resistance (TEER), a measure of intestinal barrier integrity, and peripheral blood mononuclear cell cytokine secretion, a measure of immune-stimulatory properties. We found that early-lactation lactoferrin increased TEER across Caco-2 cell layers compared with control from 10 to 48 h, mid-lactation lactoferrin did not alter TEER. We also found that early-lactation lactoferrin reduced the amount of IL-8 produced by peripheral blood mononuclear cells (compared with those treated with control medium) to a greater extent than mid-lactation lactoferrin. A pro-inflammatory chemokine, IL-8 is also known to decrease barrier function. These results suggest that the decrease in IL-8 production in the presence of early-lactation lactoferrin may be the mechanism by which it increases

  14. Lactate Metabolism is Associated with Mammalian Mitochondria

    PubMed Central

    Chen, Ying-Jr; Mahieu, Nathaniel G.; Huang, Xiaojing; Singh, Manmilan; Crawford, Peter A; Johnson, Stephen L.; Gross, Richard W.; Schaefer, Jacob

    2016-01-01

    It is well established that lactate secreted by fermenting cells can be oxidized or used as a gluconeogenic substrate by other cells and tissues. Within the fermenting cell itself, however, it is generally assumed that lactate is produced to replenish NAD+ and then is secreted. Here we explored the possibility that cytosolic lactate is metabolized by the mitochondria of fermenting mammalian cells. We found that fermenting HeLa and H460 cells utilize exogenous lactate carbon to synthesize a large percentage of their lipids. With high-resolution mass spectrometry, we found that both 13C and 2-2H labels from enriched lactate enter the mitochondria. The lactate dehydrogenase (LDH) inhibitor oxamate decreased respiration of isolated mitochondria incubated in lactate, but not isolated mitochondria incubated in pyruvate. Additionally, transmission electron microscopy (TEM) showed that LDHB localizes to the mitochondria. Taken together, our results demonstrate a link between lactate metabolism and the mitochondria of fermenting mammalian cells. PMID:27618187

  15. [Non-alcoholic fatty liver disease and steatohepatitis].

    PubMed

    Pár, Gabriella; Horváth, Gábor; Pár, Alajos

    2013-07-21

    Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, the hepatic manifestations of metabolic syndrome with close association with inzulin resistance and obesity, are the most common liver diseases, affecting up to a third of the population worldwide. They confer increased risk for hepatocellular carcinoma as well as cardiovascular diseases. The review aims to summarize advances in epidemiology, pathogenesis and clinical management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Besides liver biopsy and biomarkers, a novel non-invasive diagnostic tool the called "controlled attenuation parameter" measuring the attenuation of ultrasound generated by the transient elastography transducer, can quantitatively assess the hepatic fat content and differentiate between steatosis grades. At the same time, liver stiffness (fibrosis) can also be evaluated. The authors present their own results obtained with the latter procedure. In non-alcoholic fatty liver disease, the lifestyle intervention, weight loss, diet and exercise supported by cognitive behavioural therapy represent the basis of management. Components of metabolic syndrome (obesity, dyslipidaemia, diabetes and arterial hypertension) have to be treated. Although there is no approved pharmacological therapy for NASH, it seems that long lasting administration of vitamin E in association with high dose ursodeoxycholic acid may be beneficial. In addition, omega-3 polyunsaturated fatty acid substitution can also decrease liver fat, however, the optimal dose is not known yet. Further controlled clinical studies are warranted to establish the real value of any suggested treatment modalities for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, although these are in experimental phase yet.

  16. Nonalcoholic fatty liver disease and type 2 diabetes in obese children.

    PubMed

    Hecht, Lior; Weiss, Ram

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is commonly found in adults and adolescents with type 2 diabetes (T2DM). The cause-effect relations of these 2 conditions are complex and it is difficult to decipher whether one drives the other or vice versa. Genetic predispositions, along with obesity, are probably shared culprits of both. NAFLD may precede the diagnosis of diabetes and play a critical role of driving its development by way of increasing hepatic and whole body insulin resistance. On the other hand, T2DM is associated with hyperinsulinemia, a resistance to some of the effects of gut derived peptides and increased systemic free fatty acids, that can all promote hepatic lipid deposition. Thus, each condition may promote the development of the other and their mutual presence creates a vicious cycle. Upon studying this complex interplay from another angle, reduction of liver fat significantly improves glucose metabolism in patients with T2DM highlighting the tight pathophysiological link between them.

  17. Cell-cell and intracellular lactate shuttles.

    PubMed

    Brooks, George A

    2009-12-01

    Once thought to be the consequence of oxygen lack in contracting skeletal muscle, the glycolytic product lactate is formed and utilized continuously in diverse cells under fully aerobic conditions. 'Cell-cell' and 'intracellular lactate shuttle' concepts describe the roles of lactate in delivery of oxidative and gluconeogenic substrates as well as in cell signalling. Examples of the cell-cell shuttles include lactate exchanges between between white-glycolytic and red-oxidative fibres within a working muscle bed, and between working skeletal muscle and heart, brain, liver and kidneys. Examples of intracellular lactate shuttles include lactate uptake by mitochondria and pyruvate for lactate exchange in peroxisomes. Lactate for pyruvate exchanges affect cell redox state, and by itself lactate is a ROS generator. In vivo, lactate is a preferred substrate and high blood lactate levels down-regulate the use of glucose and free fatty acids (FFA). As well, lactate binding may affect metabolic regulation, for instance binding to G-protein receptors in adipocytes inhibiting lipolysis, and thus decreasing plasma FFA availability. In vitro lactate accumulation upregulates expression of MCT1 and genes coding for other components of the mitochondrial reticulum in skeletal muscle. The mitochondrial reticulum in muscle and mitochondrial networks in other aerobic tissues function to establish concentration and proton gradients necessary for cells with high mitochondrial densities to oxidize lactate. The presence of lactate shuttles gives rise to the realization that glycolytic and oxidative pathways should be viewed as linked, as opposed to alternative, processes, because lactate, the product of one pathway, is the substrate for the other.

  18. Cell–cell and intracellular lactate shuttles

    PubMed Central

    Brooks, George A

    2009-01-01

    Once thought to be the consequence of oxygen lack in contracting skeletal muscle, the glycolytic product lactate is formed and utilized continuously in diverse cells under fully aerobic conditions. ‘Cell–cell’ and ‘intracellular lactate shuttle’ concepts describe the roles of lactate in delivery of oxidative and gluconeogenic substrates as well as in cell signalling. Examples of the cell–cell shuttles include lactate exchanges between between white-glycolytic and red-oxidative fibres within a working muscle bed, and between working skeletal muscle and heart, brain, liver and kidneys. Examples of intracellular lactate shuttles include lactate uptake by mitochondria and pyruvate for lactate exchange in peroxisomes. Lactate for pyruvate exchanges affect cell redox state, and by itself lactate is a ROS generator. In vivo, lactate is a preferred substrate and high blood lactate levels down-regulate the use of glucose and free fatty acids (FFA). As well, lactate binding may affect metabolic regulation, for instance binding to G-protein receptors in adipocytes inhibiting lipolysis, and thus decreasing plasma FFA availability. In vitro lactate accumulation upregulates expression of MCT1 and genes coding for other components of the mitochondrial reticulum in skeletal muscle. The mitochondrial reticulum in muscle and mitochondrial networks in other aerobic tissues function to establish concentration and proton gradients necessary for cells with high mitochondrial densities to oxidize lactate. The presence of lactate shuttles gives rise to the realization that glycolytic and oxidative pathways should be viewed as linked, as opposed to alternative, processes, because lactate, the product of one pathway, is the substrate for the other. PMID:19805739

  19. Effects of compression stockings during exercise and recovery on blood lactate kinetics.

    PubMed

    Rimaud, Diana; Messonnier, Laurent; Castells, Josiane; Devillard, Xavier; Calmels, Paul

    2010-09-01

    This study aimed to investigate if wearing compression stockings (CS) during exercise and recovery could affect lactate profile in sportsmen. Eight young healthy trained male subjects performed two maximal exercise tests on a cycle ergometer on two different occasions performed randomly: CS during both exercise and recovery, and no CS. Blood lactate concentration was taken during exercise and at 0, 3, 5, 10, 15, 30 and 60 min post-exercise. The individual blood lactate recovery curves were fitted to a biexponential time function: La(t) = La(0) + A1(1 - e(-gamma1t)) + A2(1 - e(-gamma2t)), where gamma(1) and gamma(2) denote the abilities to exchange lactate between the previously active muscles and the blood and to remove lactate from the organism, respectively. A significantly higher blood lactate value at the end of the maximal exercise was found (12.1 +/- 0.5 vs. 10.8 +/- 0.5 mmol l(-1)) wearing CS as compared to no CS (P < 0.05). Lower gamma(1) and higher gamma(2) values were observed with CS during recovery, as compared to no CS. It was concluded that CS during graded exercise leads to a significant higher blood lactate value at exhaustion. Since lactate exchanges were expected to be decreased during exercise due to CS, this result was likely attributable to a higher lactate accumulation related to a greater overall contribution of anaerobic glycolysis. Although the lactate removal ability was significantly improved when wearing CS during recovery, its efficacy in promoting blood lactate clearance after high-intensity exercise is limited.

  20. 21 CFR 582.5311 - Ferrous lactate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ferrous lactate. 582.5311 Section 582.5311 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5311 Ferrous lactate. (a) Product. Ferrous lactate. (b) Conditions of use. This substance...

  1. 21 CFR 582.1207 - Calcium lactate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Calcium lactate. 582.1207 Section 582.1207 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1207 Calcium lactate. (a) Product. Calcium lactate. (b) Conditions of use. This substance...

  2. 21 CFR 582.1207 - Calcium lactate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Calcium lactate. 582.1207 Section 582.1207 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1207 Calcium lactate. (a) Product. Calcium lactate. (b) Conditions of use. This substance...

  3. 21 CFR 582.1207 - Calcium lactate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Calcium lactate. 582.1207 Section 582.1207 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1207 Calcium lactate. (a) Product. Calcium lactate. (b) Conditions of use. This substance...

  4. 21 CFR 582.1207 - Calcium lactate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium lactate. 582.1207 Section 582.1207 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1207 Calcium lactate. (a) Product. Calcium lactate. (b) Conditions of use. This substance...

  5. 21 CFR 582.1207 - Calcium lactate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Calcium lactate. 582.1207 Section 582.1207 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1207 Calcium lactate. (a) Product. Calcium lactate. (b) Conditions of use. This substance...

  6. 21 CFR 582.5311 - Ferrous lactate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ferrous lactate. 582.5311 Section 582.5311 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5311 Ferrous lactate. (a) Product. Ferrous lactate. (b) Conditions of use. This substance...

  7. 21 CFR 582.5311 - Ferrous lactate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ferrous lactate. 582.5311 Section 582.5311 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5311 Ferrous lactate. (a) Product. Ferrous lactate. (b) Conditions of use. This substance...

  8. 21 CFR 582.5311 - Ferrous lactate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ferrous lactate. 582.5311 Section 582.5311 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5311 Ferrous lactate. (a) Product. Ferrous lactate. (b) Conditions of use. This substance...

  9. Expression of Lactate Dehydrogenase in Aspergillus niger for L-Lactic Acid Production

    PubMed Central

    Dave, Khyati K.; Punekar, Narayan S.

    2015-01-01

    Different engineered organisms have been used to produce L-lactate. Poor yields of lactate at low pH and expensive downstream processing remain as bottlenecks. Aspergillus niger is a prolific citrate producer and a remarkably acid tolerant fungus. Neither a functional lactate dehydrogenase (LDH) from nor lactate production by A. niger is reported. Its genome was also investigated for the presence of a functional ldh. The endogenous A. niger citrate synthase promoter relevant to A. niger acidogenic metabolism was employed to drive constitutive expression of mouse lactate dehydrogenase (mldhA). An appraisal of different branches of the A. niger pyruvate node guided the choice of mldhA for heterologous expression. A high copy number transformant C12 strain, displaying highest LDH specific activity, was analyzed under different growth conditions. The C12 strain produced 7.7 g/l of extracellular L-lactate from 60 g/l of glucose, in non-neutralizing minimal media. Significantly, lactate and citrate accumulated under two different growth conditions. Already an established acidogenic platform, A. niger now promises to be a valuable host for lactate production. PMID:26683313

  10. Expression of Lactate Dehydrogenase in Aspergillus niger for L-Lactic Acid Production.

    PubMed

    Dave, Khyati K; Punekar, Narayan S

    2015-01-01

    Different engineered organisms have been used to produce L-lactate. Poor yields of lactate at low pH and expensive downstream processing remain as bottlenecks. Aspergillus niger is a prolific citrate producer and a remarkably acid tolerant fungus. Neither a functional lactate dehydrogenase (LDH) from nor lactate production by A. niger is reported. Its genome was also investigated for the presence of a functional ldh. The endogenous A. niger citrate synthase promoter relevant to A. niger acidogenic metabolism was employed to drive constitutive expression of mouse lactate dehydrogenase (mldhA). An appraisal of different branches of the A. niger pyruvate node guided the choice of mldhA for heterologous expression. A high copy number transformant C12 strain, displaying highest LDH specific activity, was analyzed under different growth conditions. The C12 strain produced 7.7 g/l of extracellular L-lactate from 60 g/l of glucose, in non-neutralizing minimal media. Significantly, lactate and citrate accumulated under two different growth conditions. Already an established acidogenic platform, A. niger now promises to be a valuable host for lactate production.

  11. Probiotics as a Novel Treatment for Non-Alcoholic Fatty Liver Disease; A Systematic Review on the Current Evidences

    PubMed Central

    Kelishadi, Roya; Farajian, Sanam; Mirlohi, Maryam

    2013-01-01

    Context Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, with 5-10% of liver having extra fat. Increase in its prevalence in all age groups is linked with obesity and Type II diabetes. The treatment of NAFLD remains controversial. A growing body of evidence suggests a relation between overgrowth of gut microbiota with NAFLD and non-alcoholic steatohepatitis (NASH). The objective of this review is to provide an overview on experimental and clinical studies assessing all positive and negative effects of probiotics. Evidence Acquisition We made a critical appraisal on various types of documents published from 1999 to March 2012 in journals, electronic books, seminars, and symposium contexts including Medline, PubMed, and Cochrane Central Register of Controlled Trials databases. We used the key words: “non-alcoholic fatty liver disease, probiotics, non-alcoholic steatohepatitis, liver disease, and fatty liver”. Results Probiotics, as biological factors, control the gut microbiota and result in its progression. It is in this sense that they are suggestive of a new and a natural way of promoting liver function. Correspondingly, limited evidence suggests that probiotics could be considered as a new way of treatment for NAFLD. Conclusions Various experimental studies and clinical trials revealed promising effects of probiotics in improving NAFLD; however given the limited experience in this field, generalization of probiotics as treatment of NAFLD needs substantiation through more trials with a larger sample sizes and with longer-term follow up. PMID:23885277

  12. Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis.

    PubMed

    Alonso, Cristina; Fernández-Ramos, David; Varela-Rey, Marta; Martínez-Arranz, Ibon; Navasa, Nicolás; Van Liempd, Sebastiaan M; Lavín Trueba, José L; Mayo, Rebeca; Ilisso, Concetta P; de Juan, Virginia G; Iruarrizaga-Lejarreta, Marta; delaCruz-Villar, Laura; Mincholé, Itziar; Robinson, Aaron; Crespo, Javier; Martín-Duce, Antonio; Romero-Gómez, Manuel; Sann, Holger; Platon, Julian; Van Eyk, Jennifer; Aspichueta, Patricia; Noureddin, Mazen; Falcón-Pérez, Juan M; Anguita, Juan; Aransay, Ana M; Martínez-Chantar, María Luz; Lu, Shelly C; Mato, José M

    2017-05-01

    Nonalcoholic fatty liver disease (NAFLD) is a consequence of defects in diverse metabolic pathways that involve hepatic accumulation of triglycerides. Features of these aberrations might determine whether NAFLD progresses to nonalcoholic steatohepatitis (NASH). We investigated whether the diverse defects observed in patients with NAFLD are caused by different NAFLD subtypes with specific serum metabolomic profiles, and whether these can distinguish patients with NASH from patients with simple steatosis. We collected liver and serum from methionine adenosyltransferase 1a knockout (MAT1A-KO) mice, which have chronically low levels of hepatic S-adenosylmethionine (SAMe) and spontaneously develop steatohepatitis, as well as C57Bl/6 mice (controls); the metabolomes of all samples were determined. We also analyzed serum metabolomes of 535 patients with biopsy-proven NAFLD (353 with simple steatosis and 182 with NASH) and compared them with serum metabolomes of mice. MAT1A-KO mice were also given SAMe (30 mg/kg/day for 8 weeks); liver samples were collected and analyzed histologically for steatohepatitis. Livers of MAT1A-KO mice were characterized by high levels of triglycerides, diglycerides, fatty acids, ceramides, and oxidized fatty acids, as well as low levels of SAMe and downstream metabolites. There was a correlation between liver and serum metabolomes. We identified a serum metabolomic signature associated with MAT1A-KO mice that also was present in 49% of the patients; based on this signature, we identified 2 NAFLD subtypes. We identified specific panels of markers that could distinguish patients with NASH from patients with simple steatosis for each subtype of NAFLD. Administration of SAMe reduced features of steatohepatitis in MAT1A-KO mice. In an analysis of serum metabolomes of patients with NAFLD and MAT1A-KO mice with steatohepatitis, we identified 2 major subtypes of NAFLD and markers that differentiate steatosis from NASH in each subtype. These might be

  13. Gut–Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Poeta, Marco; Pierri, Luca; Vajro, Pietro

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most frequent type of chronic liver disease in the pediatric age group, paralleling an obesity pandemic. A “multiple-hit” hypothesis has been invoked to explain its pathogenesis. The “first hit” is liver lipid accumulation in obese children with insulin resistance. In the absence of significant lifestyle modifications leading to weight loss and increased physical activity, other factors may act as “second hits” implicated in liver damage progression leading to more severe forms of inflammation and hepatic fibrosis. In this regard, the gut–liver axis (GLA) seems to play a central role. Principal players are the gut microbiota, its bacterial products, and the intestinal barrier. A derangement of GLA (namely, dysbiosis and altered intestinal permeability) may promote bacteria/bacterial product translocation into portal circulation, activation of inflammation via toll-like receptors signaling in hepatocytes, and progression from simple steatosis to non-alcoholic steato-hepatitis (NASH). Among other factors a relevant role has been attributed to the farnesoid X receptor, a nuclear transcriptional factor activated from bile acids chemically modified by gut microbiota (GM) enzymes. The individuation and elucidation of GLA derangement in NAFLD pathomechanisms is of interest at all ages and especially in pediatrics to identify new therapeutic approaches in patients recalcitrant to lifestyle changes. Specific targeting of gut microbiota via pre-/probiotic supplementation, feces transplantation, and farnesoid X receptor modulation appear promising. PMID:28767077

  14. Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis

    PubMed Central

    Katayama, Akihiro; Nakatsuka, Atsuko; Eguchi, Jun; Murakami, Kazutoshi; Teshigawara, Sanae; Kanzaki, Motoko; Nunoue, Tomokazu; Hida, Kazuyuki; Wada, Nozomu; Yasunaka, Tetsuya; Ikeda, Fusao; Takaki, Akinobu; Yamamoto, Kazuhide; Kiyonari, Hiroshi; Makino, Hirofumi; Wada, Jun

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Gpnmb is classified as a type 1 membrane protein and its soluble form is secreted by ADAM10-mediated cleavage. Gpnmb mRNA was found in the Kupffer cells and white adipose tissues (WATs) and its upregulation in obesity was recently found. Here, we generated aP2 promoter-driven Gpnmb transgenic (Tg) mice and the overexpression of Gpnmb ameliorated the fat accumulation and fibrosis of the liver in diet-induced obesity model. Soluble form of Gpnmb in sera was elevated in Gpnmb Tg mice and Gpnmb concentrated in hepatic macrophages and stellate cells interacted with calnexin, which resulted in the reduction of oxidative stress. In the patients with non-alcoholic steatohepatitis, serum soluble GPNMB concentrations were higher compared with the patients with simple steatosis. The GPNMB is a promising biomarker and therapeutic target for the development and progression of NAFLD in obesity. PMID:26581806

  15. Non-alcoholic fatty liver disease in obese adults: clinical aspects and current management strategies.

    PubMed

    Pallayova, M; Taheri, S

    2014-10-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder whose prevalence is strongly linked to the current epidemic of obesity in many western countries. The prevalence of NAFLD is two to four times higher in populations with pre-existing metabolic comorbidities than in the general population. The diagnosis of primary NAFLD involves establishing the presence of hepatic steatosis or steatohepatitis by imaging or histology, along with establishing the non-alcoholic nature of the disease process and excluding competing aetiologies for hepatic steatosis. Among the indirect serum biomarkers, the NAFLD fibrosis score can help to identify patients with NAFLD and with higher likelihood of having fibrosis or cirrhosis. A liver biopsy should be considered in NAFLD patients at increased risk for steatohepatitis/advanced fibrosis and in cases where a liver biopsy is necessary to exclude co-existing chronic liver diseases and other aetiologies for hepatic steatosis. The treatment and management recommendations for obesity-associated NAFLD are aimed towards weight reduction. The currently available interventions employed to promote weight loss and improve the metabolic responses in NAFLD include lifestyle modification, pharmacotherapy and bariatric surgery.

  16. Development of gene polymorphisms in meditators of nonalcoholic fatty liver disease

    PubMed Central

    Wang, Chun; Gong, Jianping; Wu, Hao

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, the morbidity of which closely correlates with diversity of ethnicity, minority, family and location. Its histology spans from simple steatosis, to nonalcoholic steatohepatitis, which ultimately results in fibrosis, cirrhosis and hepatocellular carcinoma. The accelerating prevalence of NAFLD is due to an incremental incidence of metabolic syndrome that is distinguished by dyslipidemia, glucose impairment, obesity, excessive oxidative stress and adipocytokine impairment. Additionally, the pathogenesis of NAFLD is thought to be a multifactorial and complicated disease associated with lifestyle habits, nutritional factors and genetics. However, the pathogenesis and underlying mechanism in the development of NAFLD caused by genetics remains unclear. People have been increasingly emphasizing on the relationship between NAFLD and gene polymorphisms in recent years, with the aim of having a comprehensive elucidation of associated gene polymorphisms influencing the pathogenesis of the disease. In the current article, the authors attempted to critically summarize the most recently identified gene polymorphisms from the facets of glucose metabolism, fatty acid metabolism, oxidative stress and related cytokines in NAFLD that contribute to promoting the progression of the disease. PMID:28804621

  17. Non-alcoholic fatty liver disease, obesity and the metabolic syndrome.

    PubMed

    Dietrich, Peter; Hellerbrand, Claus

    2014-08-01

    Nonalcoholic fatty liver disease (NAFLD) is now recognized as the most common cause of chronic liver disease worldwide. Its prevalence has increased to more than 30% of adults in developed countries and its incidence is still rising. The majority of patients with NAFLD have simple steatosis but in up to one third of patients, NAFLD progresses to its more severe form nonalcoholic steatohepatitis (NASH). NASH is characterized by liver inflammation and injury thereby determining the risk to develop liver fibrosis and cancer. NAFLD is considered the hepatic manifestation of the metabolic syndrome. However, the liver is not only a passive target but affects the pathogenesis of the metabolic syndrome and its complications. Conversely, pathophysiological changes in other organs such as in the adipose tissue, the intestinal barrier or the immune system have been identified as triggers and promoters of NAFLD progression. This article details the pathogenesis of NAFLD along with the current state of its diagnosis and treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Metabolic syndrome and nonalcoholic fatty liver disease: Is insulin resistance the link?

    PubMed

    Asrih, Mohamed; Jornayvaz, François R

    2015-12-15

    Metabolic syndrome (MetS) is a disease composed of different risk factors such as obesity, type 2 diabetes or dyslipidemia. The prevalence of this syndrome is increasing worldwide in parallel with the rise in obesity. Nonalcoholic fatty liver disease (NAFLD) is now the most frequent chronic liver disease in western countries, affecting more than 30% of the general population. NAFLD encompasses a spectrum of liver manifestations ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis, which may ultimately progress to hepatocellular carcinoma. There is accumulating evidence supporting an association between NAFLD and MetS. Indeed, NAFLD is recognized as the liver manifestation of MetS. Insulin resistance is increasingly recognized as a key factor linking MetS and NAFLD. Insulin resistance is associated with excessive fat accumulation in ectopic tissues, such as the liver, and increased circulating free fatty acids, which can further promote inflammation and endoplasmic reticulum stress. This in turn aggravates and maintains the insulin resistant state, constituting a vicious cycle. Importantly, evidence shows that most of the patients developing NAFLD present at least one of the MetS traits. This review will define MetS and NAFLD, provide an overview of the common pathophysiological mechanisms linking MetS and NAFLD, and give a perspective regarding treatment of these ever growing metabolic diseases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Current pharmacological therapies for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    PubMed

    Takahashi, Yoshihisa; Sugimoto, Keiichiro; Inui, Hiroshi; Fukusato, Toshio

    2015-04-07

    Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is considered to be a hepatic manifestation of metabolic syndrome, and its incidence is rapidly increasing worldwide. It is currently the most common chronic liver disease. NASH can progress to liver cirrhosis and hepatocellular carcinoma, and may result in liver-related death. Currently, the principal treatment for NAFLD/NASH is lifestyle modification by diet and exercise. However, pharmacological therapy is indispensable because obese patients with NAFLD often have difficulty maintaining improved lifestyles. The pathogenesis of NAFLD/NASH has not been completely elucidated. However, insulin resistance, inflammatory cytokines, and oxidative stress are thought to be important in the development and/or progression of the disease. Currently, insulin sensitizers (thiazolidinediones) and antioxidants (vitamin E) seem to be the most promising therapeutic agents for NAFLD/NASH, and lipid-lowering drugs, pentoxifylline, angiotensin receptor blockers, and n-3 polyunsaturated fatty acids also have promise. However, there is a lack of consensus regarding the most effective and appropriate pharmacotherapy for NAFLD/NASH. Animal experiments suggest that herbal medicines and natural products may be promising therapeutic agents for NAFLD/NASH, but their efficacy and safety are yet to be investigated in human studies. In this paper, we review the existing and potential pharmacological therapies for NAFLD/NASH.

  20. Th17 involvement in nonalcoholic fatty liver disease progression to non-alcoholic steatohepatitis

    PubMed Central

    Chackelevicius, Carla Melisa; Gambaro, Sabrina Eliana; Tiribelli, Claudio; Rosso, Natalia

    2016-01-01

    The nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD encompasses a wide histological spectrum ranging from benign simple steatosis to non-alcoholic steatohepatitis (NASH). Sustained inflammation in the liver is critical in this process. Hepatic macrophages, including liver resident macropaghes (Kupffer cells), monocytes infiltrating the injured liver, as well as specific lymphocytes subsets play a pivotal role in the initiation and perpetuation of the inflammatory response, with a major deleterious impact on the progression of fatty liver to fibrosis. During the last years, Th17 cells have been involved in the development of inflammation not only in liver but also in other organs, such as adipose tissue or lung. Differentiation of a naïve T cell into a Th17 cell leads to pro-inflammatory cytokine and chemokine production with subsequent myeloid cell recruitment to the inflamed tissue. Th17 response can be mitigated by T regulatory cells that secrete anti-inflammatory cytokines. Both T cell subsets need TGF-β for their differentiation and a characteristic plasticity in their phenotype may render them new therapeutic targets. In this review, we discuss the role of the Th17 pathway in NAFLD progression to NASH and to liver fibrosis analyzing different animal models of liver injury and human studies. PMID:27895397

  1. Non-invasive diagnosis of nonalcoholic fatty liver and nonalcoholic steatohepatitis.

    PubMed

    Adams, Leon A; Feldstein, Ariel E

    2011-02-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the USA and many other parts of the world. Its prevalence continues to rise; currently affecting about one in four adults and 10% of children in the USA. NAFLD represents a wide spectrum of conditions ranging from fatty liver, which in general follows a benign, no-progressive clinical course, to nonalcoholic steatohepatitis (NASH), a more serious form of NAFLD that may progress to cirrhosis and end-stage liver disease. Currently, the diagnosis of NASH requires an invasive liver biopsy with drawbacks of sampling and interpretation error. Clinical risk factors for NASH include diabetes and the metabolic syndrome; however, these are not sufficiently predictive of the condition by themselves. Routine liver enzyme levels are not reliable; however, novel plasma hepatocyte cell death markers either alone or in combination with clinical risk factors are potential non-invasive diagnostic tools for the future. This review provides a concise overview of the role non-invasive diagnostic tools for the differentiation of fatty liver from NASH as well as for the determination of presence and extent of fibrosis.

  2. Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    PubMed

    Watanabe, Sumio; Hashimoto, Etsuko; Ikejima, Kenichi; Uto, Hirofumi; Ono, Masafumi; Sumida, Yoshio; Seike, Masataka; Takei, Yoshiyuki; Takehara, Tetsuo; Tokushige, Katsutoshi; Nakajima, Atsushi; Yoneda, Masashi; Saibara, Toshiji; Shiota, Goshi; Sakaida, Isao; Nakamuta, Makoto; Mizuta, Toshihiko; Tsubouchi, Hirohito; Sugano, Kentaro; Shimosegawa, Tooru

    2015-04-01

    Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease in industrialized countries worldwide, and has become a serious public health issue not only in Western countries but also in many Asian countries including Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis (NASH) is a progressive form of disease, which often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma. In turn, a large proportion of NAFLD/NASH is the liver manifestation of metabolic syndrome, suggesting that NAFLD/NASH plays a key role in the pathogenesis of systemic atherosclerotic diseases. Currently, a definite diagnosis of NASH requires liver biopsy, though various noninvasive measures are under development. The mainstays of prevention and treatment of NAFLD/NASH include dietary restriction and exercise; however, pharmacological approaches are often necessary. Currently, vitamin E and thiazolidinedione derivatives are the most evidence-based therapeutic options, although the clinical evidence for long-term efficacy and safety is limited. This practice guideline for NAFLD/NASH, established by the Japanese Society of Gastroenterology in cooperation with The Japan Society of Hepatology, covers lines of clinical evidence reported internationally in the period starting from 1983 to January 2012, and each clinical question was evaluated using the GRADE system. Based on the primary release of the full version in Japanese, this English summary provides the core essentials of this clinical practice guideline comprising the definition, diagnosis, and current therapeutic recommendations for NAFLD/NASH in Japan.

  3. Th17 involvement in nonalcoholic fatty liver disease progression to non-alcoholic steatohepatitis.

    PubMed

    Chackelevicius, Carla Melisa; Gambaro, Sabrina Eliana; Tiribelli, Claudio; Rosso, Natalia

    2016-11-07

    The nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD encompasses a wide histological spectrum ranging from benign simple steatosis to non-alcoholic steatohepatitis (NASH). Sustained inflammation in the liver is critical in this process. Hepatic macrophages, including liver resident macropaghes (Kupffer cells), monocytes infiltrating the injured liver, as well as specific lymphocytes subsets play a pivotal role in the initiation and perpetuation of the inflammatory response, with a major deleterious impact on the progression of fatty liver to fibrosis. During the last years, Th17 cells have been involved in the development of inflammation not only in liver but also in other organs, such as adipose tissue or lung. Differentiation of a naïve T cell into a Th17 cell leads to pro-inflammatory cytokine and chemokine production with subsequent myeloid cell recruitment to the inflamed tissue. Th17 response can be mitigated by T regulatory cells that secrete anti-inflammatory cytokines. Both T cell subsets need TGF-β for their differentiation and a characteristic plasticity in their phenotype may render them new therapeutic targets. In this review, we discuss the role of the Th17 pathway in NAFLD progression to NASH and to liver fibrosis analyzing different animal models of liver injury and human studies.

  4. Sirtuins and nonalcoholic fatty liver disease

    PubMed Central

    Nassir, Fatiha; Ibdah, Jamal A

    2016-01-01

    Mammalian sirtuins are seven members belonging to the silent information regulator 2 family, a group of Class III histone/protein deacetylases. Sirtuins (SIRT 1-7) have different subcellular localization and function and they regulate cellular protein function through various posttranslational modifications. SIRT1 and 3, the most studied sirtuins, use the product of cellular metabolism nicotinamide adenine dinucleotide as a cofactor to post-translationally deacetylate cellular proteins and consequently link the metabolic status of the cell to protein function. Sirtuins have been shown to play a key role in the development and rescue of various metabolic diseases including non-alcoholic fatty liver disease (NAFLD). NAFLD is currently the most chronic liver disease due mainly to high-calorie consumption and lower physical activity. No pharmacological approach is available to treat NAFLD, the current recommended treatment are lifestyle modification such as weight loss through calorie restriction and exercise. Recent studies have shown downregulation of sirtuins in human as well as animal models of NAFLD indicating an important role of sirtuins in the dynamic pathophysiology of NAFLD. In this review, we highlight the recent knowledge on sirtuins, their role in NAFLD and their unique potential role as novel therapeutic target for NAFLD treatment. PMID:28028356

  5. Endocrine causes of nonalcoholic fatty liver disease.

    PubMed

    Marino, Laura; Jornayvaz, François R

    2015-10-21

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed.

  6. [Nonalcoholic fatty liver disease in children].

    PubMed

    Bojórquez-Ramos, María del Carmen

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of liver disease in children and adolescents in the United States of America (USA) and probably in the entire western hemisphere, due to the increase in the prevalence of overweight and obesity. Steatosis can progress to inflammation, fibrosis and even cirrhosis, which increases the morbidity and mortality associated to liver disease. In every overweight and obese child a thorough analysis should be performed including liver function tests and liver ultrasound, in order to establish a timely diagnosis. The liver biopsy is the most specific study to rule out other potentially treatable entities. It is necessary to count on non-invasive methods to detect children with NAFLD and identify those in risk of progression. Biomarkers related to inflammation, oxidative stress, apoptosis and fibrosis have been reported. The main goal of the treatment is to modify the life style, starting with a healthy diet and an increase of physical activity. Regarding pharmacological treatment, there is evidence of histological improvement with vitamin E use, as opposed to metformin, but more conclusive studies regarding this subject are needed.

  7. Developmental origins of nonalcoholic fatty liver disease.

    PubMed

    Brumbaugh, David E; Friedman, Jacob E

    2014-01-01

    Obese pregnant women may transmit their metabolic phenotype to offspring, leading to a cycle of obesity and diabetes over generations. Early childhood obesity predicts nonalcoholic fatty liver disease (NAFLD), the most common chronic human liver disease. The fetus may be vulnerable to steatosis because immature fetal adipose depots are not available to buffer the excess transplacental lipid delivery in maternal obesity. In animal models, in utero high-fat diet exposure results in an increase in the accumulation of liver triglycerides in offspring and increased hepatic oxidative stress and apoptosis, perhaps priming the liver for later development of NAFLD. Innate immune dysfunction and necroinflammatory changes have been observed in postnatal offspring liver of animals born to high-fat-fed dams. Postweaning, livers of offspring exposed to maternal high-fat feeding in utero share pathophysiologic features with human NAFLD, including increased de novo lipogenesis and decreased free fatty acid oxidation. Human studies using magnetic resonance imaging have shown that maternal BMI predicts infant intrahepatocellular lipid storage, as seen in animal models. The generational transfer of NAFLD may occur via epigenetic changes in offspring liver. Transmission of microbiota from mother to infant may impact energy retention and immune function that contribute to a predisposition to NAFLD.

  8. Endocrine causes of nonalcoholic fatty liver disease

    PubMed Central

    Marino, Laura; Jornayvaz, François R

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed. PMID:26494962

  9. Bariatric surgery and nonalcoholic fatty liver disease.

    PubMed

    Bower, Guy; Athanasiou, Thanos; Isla, Alberto M; Harling, Leanne; Li, Jia V; Holmes, Elaine; Efthimiou, Evangelos; Darzi, Ara; Ashrafian, Hutan

    2015-07-01

    The rising prevalence of nonalcoholic fatty liver disease (NAFLD) is associated with the increasing global pandemic of obesity. These conditions cluster with type II diabetes mellitus and the metabolic syndrome to result in obesity-associated liver disease. The benefits of bariatric procedures on diabetes and the metabolic syndrome have been recognized for some time, and there is now mounting evidence to suggest that bariatric procedures improve liver histology and contribute to the beneficial resolution of NAFLD in obese patients. These beneficial effects derive from a number of weight-dependent and weight-independent mechanisms including surgical BRAVE actions (bile flow changes, restriction of stomach size, anatomical gastrointestinal rearrangement, vagal manipulation, enteric hormonal modulation) and subsequent effects such as reduced lipid intake, adipocytokine secretion, modulation of gut flora, improvements in insulin resistance and reduced inflammation. Here, we review the clinical investigations on bariatric procedures for NAFLD, in addition to the mounting mechanistic data supporting these findings. Elucidating the mechanisms by which bariatric procedures may resolve NAFLD can help enhance surgical approaches for metabolic hepatic dysfunction and also contribute toward developing the next generation of therapies aimed at reducing the burden of obesity-associated liver disease.

  10. Nonalcoholic fatty liver disease and statins.

    PubMed

    Tziomalos, Konstantinos; Athyros, Vasilios G; Paschos, Paschalis; Karagiannis, Asterios

    2015-10-01

    Nonalcoholic fatty liver disease (NAFLD) is the most frequent cause of elevated transaminase levels and affects approximately one third of the general population. Patients with NAFLD are at increased risk for cardiovascular events, which represent the leading cause of death in this population. We discuss the safety and efficacy of statins in this population. We reviewed the most recent literature on the safety of statins in patients with NAFLD and on their effects on liver histology and cardiovascular events. It appears that statins can be safely administered to patients with NAFLD, including those with elevated transaminase levels (<3 times the upper limit of normal). Post-hoc analyses of randomized controlled trials also suggest that statins might reduce cardiovascular morbidity in this population. On the other hand, there are few and controversial data on the effects of statins on liver histology in patients with NAFLD. Statins appear to be safe and might also reduce cardiovascular events in patients with NAFLD. Ongoing and future studies will clarify whether statins might also have a role in the treatment of NAFLD. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Nonalcoholic Lipid Accumulation and Hepatocyte Malignant Transformation

    PubMed Central

    Gu, Juanjuan; Yao, Min; Yao, Dengbing; Wang, Li; Yang, Xuli; Yao, Dengfu

    2016-01-01

    Abstract Worldwide incidence of hepatocellular carcinoma (HCC) is steadily increasing, highlighting its status as a public health concern, particularly due to its significant association with other comorbidities, such as diabetes. However, nonalcoholic fatty liver disease (NAFLD) has emerged as a primary risk factor, with its own prevalence increasing in recent years, and it has gradually caught up with the historical primary etiological factors of infection with hepatitis B virus and hepatitis C virus, exposure to aflatoxin, or alcohol liver disease. The deeply worrisome aspects of all of these high risk factors, however, are their remarkable presence within populations. Systemic and genetic mechanisms involved in the malignant transformation of liver cells, as well as useful biomarkers of early stage HCC are being investigated. However, the exact mechanisms underlying the interrelation of NAFLD and HCC remain largely unknown. In this review, some of the recent advances in our understanding of liver lipid accumulation are summarized and discussed to provide insights into the relationship between NAFLD and hepatocyte malignant transformation. PMID:27350942

  12. Psoriasis and Nonalcoholic Fatty Liver Disease.

    PubMed

    Carrascosa, J M; Bonanad, C; Dauden, E; Botella, R; Olveira-Martín, A

    2017-03-16

    Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver condition in the West. The prevalence and severity of NAFLD is higher and the prognosis worse in patients with psoriasis. The pathogenic link between psoriasis and NAFLD is chronic inflammation and peripheral insulin resistance, a common finding in diseases associated with psoriasis. NAFLD should therefore be ruled out during the initial evaluation of patients with psoriasis, in particular if they show signs of metabolic syndrome and require systemic treatment. Concomitant psoriasis and NAFLD and the likelihood of synergy between them place limitations on general recommendations and treatment for these patients given the potential for liver toxicity. As hepatotoxic risk is associated with some of the conventional drugs used in this setting (e.g., acitretin, methotrexate, and ciclosporin), patients prescribed these treatments should be monitored as appropriate. Anti-tumor necrosis factor agents hold the promise of potential benefits based on their effects on the inflammatory process and improving peripheral insulin resistance. However, cases of liver toxicity have also been reported in relation to these biologics. No evidence has emerged to suggest that anti-p40 or anti-interleukin 17 agents provide benefits or have adverse effects.

  13. [Non-alcoholic fatty liver disease and hepatocellular carcinoma - 2016].

    PubMed

    Pár, Alajos; Pár, Gabriella

    2016-06-19

    In the past decade non-alcoholic liver disease became the most frequently diagnosed liver disease in developed countries. At the same time, the dramatic rise in the incidence of hepatocellular carcinoma is attributed to this common metabolic disorder, and mainly to its severe form, non-alcoholic steatohepatitis. The risk factors of these associated diseases are genetic predisposition, obesity and diabetes as well as chronic low grade necro-infammation, which often leads to liver fibrosis. Free fatty acids, cytokines, lipotoxicity, insulin resistance, microRNS dysregulation and alteration in intestinal microbiota play a pivotal role in the pathogenesis. Treatment of non-alcoholic fatty liver disease - weight reduction and physical exercise in obesity, metformin in diabetes, statins in dyslipidemia and, as a new option, obeticholic acid - may diminish the risk of the hepatocellular carcinoma related to this metabolic disease.

  14. NONALCOHOLIC FATTY LIVER DISEASE BRAZILIAN SOCIETY OF HEPATOLOGY CONSENSUS.

    PubMed

    Cotrim, Helma P; Parise, Edison R; Figueiredo-Mendes, Cláudio; Galizzi-Filho, João; Porta, Gilda; Oliveira, Claudia P

    2016-01-01

    The prevalence of obesity-related metabolic syndrome has rapidly increased in Brazil, resulting in a high frequency of nonalcoholic fatty liver disease, that didn't receive much attention in the past. However, it has received increased attention since this disease was identified to progress to end-stage liver diseases, such as cirrhosis and hepatocellular carcinoma. Clinical practice guidelines for the diagnosis and treatment of nonalcoholic fatty liver disease have not been established in Brazil. The Brazilian Society of Hepatology held an event with specialists' members from all over Brazil with the purpose of producing guideline for Nonalcoholic Fatty Liver Disease based on a systematic approach that reflects evidence-based medicine and expert opinions. The guideline discussed the following subjects: 1-Concepts and recommendations; 2-Diagnosis; 3-Non-medical treatment; 4-Medical treatment; 5-Pediatrics - Diagnosis; 6-Pediatrics - Non-medical treatment; 7-Pediatrics - Medical treatment; 8-Surgical treatment.

  15. Therapeutic potential of green tea in nonalcoholic fatty liver disease.

    PubMed

    Masterjohn, Christopher; Bruno, Richard S

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a constellation of progressive liver disorders that are closely related to obesity, diabetes, and insulin resistance and may afflict over 70 million Americans. NAFLD may occur as relatively benign, nonprogressive liver steatosis, but in many individuals it may progress in severity to nonalcoholic steatohepatitis, fibrosis, cirrhosis, and liver failure or hepatocellular carcinoma. No validated treatments currently exist for NAFLD except for weight loss, which has a poor long-term success rate. Thus, dietary strategies that prevent the development of liver steatosis or its progression to nonalcoholic steatohepatitis are critically needed. Green tea is rich in polyphenolic catechins that have hypolipidemic, thermogenic, antioxidant, and anti-inflammatory activities that may mitigate the occurrence and progression of NAFLD. This review presents the experimental evidence demonstrating the hepatoprotective properties of green tea and its catechins and the proposed mechanisms by which these targeted dietary agents protect against NAFLD.

  16. Lactation space design: supporting evidence-based practice and the baby-friendly hospital initiative.

    PubMed

    Thompson, Tammy Smith; Heflin, Lashawna

    2011-01-01

    The design of spaces where lactation occurs within a healthcare facility often lacks careful attention to the environmental requirements of breastfeeding. Although numerous studies evoke overwhelming support for lactation initiation in hospitals, few designers may understand the importance of such spaces. Furthermore, many designers may be unaware of the contributions they may make to this initiative. Countless studies that support the philosophy that breast milk is the best nutritional option for babies have been conducted. There are many health and economic advantages of breastfeeding for babies, mothers, and communities. Research suggests that exclusive breastfeeding for the first 6 months of life reduces the rate of illness throughout infancy and beyond, saves lives, and could save billions of dollars in the United States each year.The Baby Friendly Hospital Initiative is a global program established to promote within healthcare facilities the facilitation of breastfeeding infants from birth. Results of this initiative show a significant increase in breastfeeding rates in many countries. The intuitive design response to such favorable research is to enhance the lactation environment, assuming that mothers who feel comfortable in lactation spaces will use them more frequently, which promotes lactation in healthcare facilities. Considering the numerous research-supported advantages of breastfeeding, designers would be prudent to seek and apply knowledge of the environmental needs to the design of lactation spaces. This may be achieved by becoming familiar with lactation procedures to understand the circulation, adjacencies, and spatial requirements of lactation programs. Incorporating this information into the design may allow the development of ideal spaces that facilitate lactation.

  17. Current Pharmacologic Therapy for Nonalcoholic Fatty Liver Disease.

    PubMed

    Ganesh, Swaytha; Rustgi, Vinod K

    2016-05-01

    Weight loss, regular exercise, and diet composition modification seem to improve biochemical and histologic abnormalities. Other therapies directed at insulin resistance, oxidative stress, cytoprotection, and fibrosis may also offer benefits. Insulin sensitizers and vitamin E seem to be the most promising; however, they cause side effects. A multifaceted approach of lifestyle modifications, weight loss, and pharmacotherapy can be used in combination, but no single treatment approach has proved universally applicable to the general population with nonalcoholic steatohepatitis (NASH). Continuous clinical and preclinical studies on existing and potential drugs are needed to improve treatment of nonalcoholic fatty liver disease/NASH.

  18. [Non-alcoholic fatty liver disease in children and adolescents].

    PubMed

    Björklund, Jessica; Laursen, Tea Lund; Kazankov, Konstantin; Thomsen, Karen Louise; Hamilton-Dutoit, Stephen; Stenbøg, Elisabeth; Grønbæk, Henning

    2017-07-03

    Non-alcoholic fatty liver disease (NAFLD) is characterized by liver fat accumulation and non-alcoholic steatohepatitis (NASH) with inflammation and fibrosis, which may lead to cirrhosis also in childhood. NAFLD/NASH in children are related to obesity and the metabolic syndrome, and incidence and prevalence are expected to increase. Children having liver steatosis and elevated liver enzymes are most often asymptomatic, and a liver biopsy is necessary for correct diagnosis and staging. The treatment should focus on lifestyle changes, as pharmacological therapy needs further evaluation.

  19. Non-alcoholic Fatty liver disease in children.

    PubMed

    Singer, Cristina; Stancu, Polixenia; Coşoveanu, Simona; Botu, Alina

    2014-01-01

    In the last years, there has been extremely much information which reveals an alarming increase of obesity in children and, at the same time, an increase of the incidence of non-alcoholic fatty liver disease (NAFLD). NAFLD implies a wide range of affections starting from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH); the latter can evolve to cirrhosis and hepatic carcinoma. All these affections were noticed in children, too. The article presents data on the epidemiology, pathogeny, clinical and paraclinical findings, and treatment of NAFLD in children.

  20. Non-Alcoholic Fatty Liver Disease in Children

    PubMed Central

    SINGER, CRISTINA; STANCU, POLIXENIA; COŞOVEANU, SIMONA; BOTU, ALINA

    2014-01-01

    In the last years, there has been extremely much information which reveals an alarming increase of obesity in children and, at the same time, an increase of the incidence of non-alcoholic fatty liver disease (NAFLD). NAFLD implies a wide range of affections starting from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH); the latter can evolve to cirrhosis and hepatic carcinoma. All these affections were noticed in children, too. The article presents data on the epidemiology, pathogeny, clinical and paraclinical findings, and treatment of NAFLD in children. PMID:25729601

  1. Nonalcoholic Fatty Liver Disease in Children: Hepatic and Extrahepatic Complications.

    PubMed

    Selvakumar, Praveen Kumar Conjeevaram; Kabbany, Mohammad Nasser; Nobili, Valerio; Alkhouri, Naim

    2017-06-01

    Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome and has become the most common form of chronic liver disease in children and adolescents. The histologic spectrum of NAFLD is broad ranging, from the relatively benign form of simple steatosis to the aggressive form of nonalcoholic steatohepatitis, eventually leading to fibrosis and cirrhosis. NAFLD has also been recognized as an independent risk factor for extrahepatic complications, such as cardiovascular disease, type 2 diabetes mellitus, sleep disorders, and osteoporosis. In this review, we discuss both the hepatic and extrahepatic complications of NAFLD in children. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Reliability of urine lactate as a novel biomarker of lactate production capacity in maximal swimming.

    PubMed

    Nikolaidis, Stefanos; Karpouzi, Christina; Tsalis, George; Kabasakalis, Athanasios; Papaioannou, Konstantinos G; Mougios, Vassilis

    2016-01-01

    Postexercise urine lactate may be a novel biomarker of lactate production capacity during exercise. To evaluate the reliability and utility of the urine lactate concentration after maximal swimming trials between different training protocols (6 × 50 m and 3 × 100 m) and training states (active and nonactive swimmers). Lactate and creatinine were determined by spectrophotometry in blood and urine. Blood and urine lactate concentrations were correlated in-between training protocols and in participants of different training states. The reliability of the urine lactate concentration was moderate for one of the training protocols and good or moderate for the two training states. Additionally, it was lower than that of the blood lactate concentration, and did not improve after normalizing to the urine creatinine concentration. Although promising as a biomarker of lactate production capacity, urine lactate requires further research to improve its reliability.

  3. Lactate production under fully aerobic conditions: the lactate shuttle during rest and exercise.

    PubMed

    Brooks, G A

    1986-12-01

    O2 insufficiency and other factors increase the rate of lactate production. Significant quantities of lactate are produced under postabsorptive as well as postprandial conditions in resting individuals. In humans during postabsorptive rest, 25-50% of the total carbohydrate combusted appears to pass through the lactate pool. During sustained submaximal (in terms of VO2max) exercise, the rates of lactate production (Ri) and oxidation (Rox) are greatly elevated as compared to rest. However, lactate production and oxidation increase relatively less than O2 consumption during moderate-intensity exercise. Because the lactate production index (RiI = Ri/VO2) decreases during submaximal, moderate-intensity exercise compared to rest, it is concluded that skeletal muscle and other sites of lactate production are effectively oxygenated. Alterations in the levels of circulating catecholamines can affect levels and turnover rates of glucose and lactate. In pure red dog gracilis muscle in situ and in the healthy and myocardium in vivo, contraction results in glycolysis and lactate production. This production of lactate occurs despite an apparent abundance of O2. Similarly, glucose catabolism in the human brain results in lactate production. The formation of lactate under fully aerobic conditions of rest and exercise represents an important mechanism by which different tissues share a carbon source (lactate) for oxidation and other processes such as gluconeogenesis. This mechanism has been termed the lactate shuttle.

  4. Inflammatory mediators in mastitis and lactation insufficiency.

    PubMed

    Ingman, Wendy V; Glynn, Danielle J; Hutchinson, Mark R

    2014-07-01

    Mastitis is a common inflammatory disease during lactation that causes reduced milk supply. A growing body of evidence challenges the central role of pathogenic bacteria in mastitis, with disease severity associated with markers of inflammation rather than infection. Inflammation in the mammary gland may be triggered by microbe-associated molecular patterns (MAMPs) as well as danger-associated molecular patterns (DAMPs) binding to pattern recognition receptors such as the toll-like receptors (TLRs) on the surface of mammary epithelial cells and local immune cell populations. Activation of the TLR4 signalling pathway and downstream nuclear factor kappa B (NFkB) is critical to mediating local mammary gland inflammation and systemic immune responses in mouse models of mastitis. However, activation of NFkB also induces epithelial cell apoptosis and reduced milk protein synthesis, suggesting that inflammatory mediators activated during mastitis promote partial involution. Perturbed milk flow, maternal stress and genetic predisposition are significant risk factors for mastitis, and could lead to a heightened TLR4-mediated inflammatory response, resulting in increased susceptibility and severity of mastitis disease in the context of low MAMP abundance. Therefore, heightened host inflammatory signalling may act in concert with pathogenic or commensal bacterial species to cause both the inflammation associated with mastitis and lactation insufficiency. Here, we present an alternate paradigm to the widely held notion that breast inflammation is driven principally by infectious bacterial pathogens, and suggest there may be other therapeutic strategies, apart from the currently utilised antimicrobial agents, that could be employed to prevent and treat mastitis in women.

  5. Lactate metabolism in the fetal rabbit lung

    SciTech Connect

    Engle, M.J.; Brown, D.J.; Dooley, M.

    1986-05-01

    Lactate is frequently overlooked as a potential substrate for the fetal lung, even though it is present in the fetal circulation in concentrations as high as 8 mM. These high concentrations, coupled with the relatively low levels of glucose in the fetal blood, may indicate that lactate can substitute for glucose in pulmonary energy generation and phospholipid synthesis. A series of experiments was therefore undertaken in order to investigate the role of lactate in perinatal pulmonary development. Explants from 30 day gestation fetal rabbit lungs were incubated in Krebs-Ringer bicarbonate buffer supplemented with 3 mM (U-/sup 14/C)-glucose and varying levels of lactate. In the absence of medium lactate, fetal rabbit lung explants were capable of producing lactate at a rate of approximately 200 etamoles/mg protein/hour. The addition of lactate to the bathing medium immediately reduced net lactate production and above 4 mM, fetal rabbit lung explants became net utilizers of lactate. Media lactate concentrations of 2.5 mM, 5 mM and 10 mM also decreased glucose incorporation into total tissue disaturated phosphatidylcholine by approximately 20%, 35%, and 45%, respectively. Glucose incorporation into surfactant phosphatidylcholine was also reduced by approximately 50%, when lactate was present in the incubation medium at a concentration of 5 mM. Additional experiments also revealed that fetal lung lactate dehydrogenase activity was almost twice that found in the adult rabbit lung. These data indicate that lactate may be an important carbon source for the developing lung and could be a significant component in the manufacture of surfactant phosphatidylcholine during late gestation.

  6. [Role of metabolic lipases and lipotoxicity in the development of non-alcoholic steatosis and non-alcoholic steatohepatitis].

    PubMed

    Berlanga, Alba; Guiu-Jurado, Esther; Porras, José Antonio; Aragonès, Gemma; Auguet, Teresa

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in developed countries, covering a spectrum of pathological conditions ranging from single steatosis to non-alcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma. Its pathogenesis has been often interpreted by the "double-hit" hypothesis, where the lipid accumulation in the liver is followed by proinflammatory mediators inducing inflammation, hepatocellular injury and fibrosis. Nowadays, a more complex model suggests that free fatty acids and their metabolites could be the true lipotoxic agents that contribute to the development of NAFLD and hepatic insulin resistance, suggesting a central role for metabolic lipases in that process.

  7. [The role of lactate besides the lactic acidosis].

    PubMed

    Brucculeri, S; Urso, C; Caimi, G

    2013-01-01

    Lactic acidosis (LA) is the most common form of metabolic acidosis defined by values of lactate greater than 5 mmol / l and by a pH <7.34. The pathogenesis of LA involves hypoxic (type A) and non hypoxic (type B) causes which are often coexisting. Lactic acidosis is usual in hospitalized population especially in subjects in intensive care units, in which lactate levels on admission could be predictors of mortality even in the absence of organ dysfunction or shock. The outcome is mainly dependent on the cardiovascular effects of acidosis. In subjects with cardiogenic shock, the increased lactate/pyruvate ratio, detectable at onset, is correladed with mortality. An early assessment of blood and tissue lactate levels could play a role in the therapeutic management as well as in outcome. LA could be a unfavorable prognostic factor in cancer. The lactate would act also as "signal molecule" and as a promoting factor in angiogenesis and tumor progression. In the presence of risk factors for LA the role of metformin may be overrated. Despite the doctrinal progress to understand the pathogenesis and pathophysiology, there is not univocal consensus on the therapeutic treatment of LA. The identification and the attempt to remove the cause of acidosis are main aims; treatment with sodium bicarbonate is a matter of debate as the data on the cardiovascular effects and mortality are unclear. The therapy with carbicarb, dichloroacetate or THAM has shown no specific advantages in terms of mortality. In experimental models of LA and shock the use of sodium-hydrogen exchanger-1 (NHE1) selective inhibitors reduces cell damage and inflammatory cytokines synthesis; it also improves cardiac performance and decreases mortality.

  8. NICU Nurses and Lactation-Based Support and Care.

    PubMed

    Froh, Elizabeth; Dahlmeier, Katherine; Spatz, Diane L

    2017-06-01

    The provision of human milk and breastfeeding is essential in the neonatal intensive care unit (NICU) population. However, recent national research has demonstrated very low percentages of NICU nurses providing lactation-based support and care to patients and families, and less than half of all NICUs have an International Board Certified Lactation Consultant (IBCLC) on staff. The purpose of this study was to describe how NICU bedside nurses are providing lactation-based support and care during their shifts and the frequency of that support. The secondary aim was to gain an understanding of the NICU nurses' attitudes toward human milk and breastfeeding. Through a prospective descriptive cohort design, the authors of this study created and disseminated a web-based survey (SurveyMonkey) of 21 questions including the Iowa Infant Feeding Attitude Scale (IIFAS) to a Northeastern urban hospital staff of bedside nurses. A total of 140 of the 389 eligible NICU bedside nurses responded to the survey. Between 50.7% and 72.9% of nurses reported to providing lactation-based support and care during the previous shift worked and during the previous week worked, respectively. The participants' responses to the IIFAS resulted in an overall score of 69.1, indicating an attitude of "positive to breastfeeding." The study demonstrates that the majority provide lactation-based support and care on every shift and hold very positive attitudes toward the provision of human milk and breastfeeding. Hospitals should be encouraged to promote educational and training programs in their respective institutions. Researchers should examine NICU nurses' attitudes and beliefs about human milk and breastfeeding on a national scale.

  9. Parental perceptions regarding lifestyle interventions for obese children and adolescents with nonalcoholic fatty liver disease.

    PubMed

    Iñiguez, Ingrid Rivera; Yap, Jason; Mager, Diana R

    2014-05-01

    Nonalcoholic fatty liver disease (NAFLD) affects 30% of obese children globally. The main treatment for NAFLD is to promote gradual weight loss through lifestyle modification. Very little is known regarding parental perspectives about the barriers and facilitators that influence the ability to promote healthy lifestyle behaviours in children with NAFLD. To explore and describe parental perspectives regarding barriers to and facilitators of implementing lifestyle modification in children with NAFLD. A mixed-methods approach, including qualitative methodology (focus groups) and validated questionnaires (Lifestyle Behaviour Checklist), was used to assess parental perceptions regarding barriers to and facilitators of lifestyle change in parents of children with healthy body weights (control parents) and in parents of children with NAFLD (NAFLD parents). NAFLD parents identified more problem behaviours related to food portion size and time spent in nonsedentary physical activity, and lower parental self-efficacy than parents of controls (P<0.05). Major barriers to lifestyle change cited by NAFLD parents were lack of time, self-motivation and role modelling of healthy lifestyle behaviours. In contrast, control parents used a variety of strategies to elicit healthy lifestyle behaviours in their children including positive role modelling, and inclusion of the child in food preparation and meal purchasing decisions, and perceived few barriers to promoting healthy lifestyles. Internet sources were the main form of nutrition information used by parents. Lifestyle modification strategies focused on promoting increased parental self-efficacy and parental motivation to promote healthy lifestyle behaviour are important components in the treatment of obese children with NAFLD.

  10. Nonalcoholic fatty liver disease - A multisystem disease?

    PubMed Central

    Mikolasevic, Ivana; Milic, Sandra; Turk Wensveen, Tamara; Grgic, Ivana; Jakopcic, Ivan; Stimac, Davor; Wensveen, Felix; Orlic, Lidija

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians. PMID:27920470

  11. Nuclear receptors and nonalcoholic fatty liver disease.

    PubMed

    Cave, Matthew C; Clair, Heather B; Hardesty, Josiah E; Falkner, K Cameron; Feng, Wenke; Clark, Barbara J; Sidey, Jennifer; Shi, Hongxue; Aqel, Bashar A; McClain, Craig J; Prough, Russell A

    2016-09-01

    Nuclear receptors are transcription factors which sense changing environmental or hormonal signals and effect transcriptional changes to regulate core life functions including growth, development, and reproduction. To support this function, following ligand-activation by xenobiotics, members of subfamily 1 nuclear receptors (NR1s) may heterodimerize with the retinoid X receptor (RXR) to regulate transcription of genes involved in energy and xenobiotic metabolism and inflammation. Several of these receptors including the peroxisome proliferator-activated receptors (PPARs), the pregnane and xenobiotic receptor (PXR), the constitutive androstane receptor (CAR), the liver X receptor (LXR) and the farnesoid X receptor (FXR) are key regulators of the gut:liver:adipose axis and serve to coordinate metabolic responses across organ systems between the fed and fasting states. Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and may progress to cirrhosis and even hepatocellular carcinoma. NAFLD is associated with inappropriate nuclear receptor function and perturbations along the gut:liver:adipose axis including obesity, increased intestinal permeability with systemic inflammation, abnormal hepatic lipid metabolism, and insulin resistance. Environmental chemicals may compound the problem by directly interacting with nuclear receptors leading to metabolic confusion and the inability to differentiate fed from fasting conditions. This review focuses on the impact of nuclear receptors in the pathogenesis and treatment of NAFLD. Clinical trials including PIVENS and FLINT demonstrate that nuclear receptor targeted therapies may lead to the paradoxical dissociation of steatosis, inflammation, fibrosis, insulin resistance, dyslipidemia and obesity. Novel strategies currently under development (including tissue-specific ligands and dual receptor agonists) may be required to separate the beneficial effects of nuclear receptor activation from unwanted metabolic

  12. Heritability of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Schwimmer, Jeffrey B.; Celedon, Manuel A.; Lavine, Joel E.; Salem, Rany; Campbell, Nzali; Schork, Nicholas J.; Shiehmorteza, Masoud; Yokoo, Takeshi; Chavez, Alyssa; Middleton, Michael S.; Sirlin, Claude B.

    2010-01-01

    Background & Aims Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States. The etiology is believed to be multi-factorial with a substantial genetic component; however, the heritability of NAFLD is undetermined. Therefore, a familial aggregation study was performed to test the hypothesis that NAFLD is highly heritable. Methods Overweight children with biopsy-proven NAFLD and overweight children without NAFLD served as probands. Family members were studied including magnetic resonance imaging to quantify liver fat fraction. Fatty liver was defined as a liver fat fraction ≥ 5%. Etiologies for fatty liver other than NAFLD were excluded. Narrow-sense heritability estimates for fatty liver (dichotomous) and fat fraction (continuous) were calculated using variance components analysis adjusted for covariate effects. Results Fatty liver was present in 17% of siblings and 37% of parents of overweight children without NAFLD. Fatty liver was significantly more common in siblings (59%) and parents (78%) of children with NAFLD. Liver fat fraction was correlated with body mass index (BMI), although the correlation was significantly stronger for families of children with NAFLD than those without NAFLD. Adjusted for age, sex, race, and BMI, heritability of fatty liver was 1.000 and of liver fat fraction 0.386. Conclusion Family members of children with NAFLD should be considered at high risk for NAFLD. These data suggest that familial factors are a major determinant of whether an individual has NAFLD. Studies examining the complex relations between genes and environment in the development and progression of NAFLD are warranted. PMID:19208353

  13. Lactate administration reproduces specific brain and liver exercise-related changes.

    PubMed

    E, Lezi; Lu, Jianghua; Selfridge, J Eva; Burns, Jeffrey M; Swerdlow, Russell H

    2013-10-01

    The effects of exercise are not limited to muscle, and its ability to mitigate some chronic diseases is under study. A more complete understanding of how exercise impacts non-muscle tissues might facilitate design of clinical trials and exercise mimetics. Here, we focused on lactate's ability to mediate changes in liver and brain bioenergetic-associated parameters. In one group of experiments, C57BL/6 mice underwent 7 weeks of treadmill exercise sessions at intensities intended to exceed the lactate threshold. Over time, the mice dramatically increased their lactate threshold. To ensure that plasma lactate accumulated during the final week, the mice were run to exhaustion. In the liver, mRNA levels of gluconeogenesis-promoting genes increased. While peroxisome proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1α) expression increased, there was a decrease in PGC-1β expression, and overall gene expression changes favored respiratory chain down-regulation. In the brain, PGC-1α and PGC-1β were unchanged, but PGC-1-related co-activator expression and mitochondrial DNA copy number increased. Brain tumor necrosis factor alpha expression fell, whereas vascular endothelial growth factor A expression rose. In another group of experiments, exogenously administered lactate was found to reproduce some but not all of these observed liver and brain changes. Our data suggest that lactate, an exercise byproduct, could mediate some of the effects exercise has on the liver and the brain, and that lactate itself can act as a partial exercise mimetic.

  14. Exogenous lactate supply affects lactate kinetics of rainbow trout, not swimming performance

    PubMed Central

    Omlin, Teye; Langevin, Karolanne

    2014-01-01

    Intense swimming causes circulatory lactate accumulation in rainbow trout because lactate disposal (Rd) is not stimulated as strongly as lactate appearance (Ra). This mismatch suggests that maximal Rd is limited by tissue capacity to metabolize lactate. This study uses exogenous lactate to investigate what constrains maximal Rd and minimal Ra. Our goals were to determine how exogenous lactate affects: 1) Ra and Rd of lactate under baseline conditions or during graded swimming, and 2) exercise performance (critical swimming speed, Ucrit) and energetics (cost of transport, COT). Results show that exogenous lactate allows swimming trout to boost maximal Rd lactate by 40% and reach impressive rates of 56 μmol·kg−1·min−1. This shows that the metabolic capacity of tissues for lactate disposal is not responsible for setting the highest Rd normally observed after intense swimming. Baseline endogenous Ra (resting in normoxic water) is not significantly reduced by exogenous lactate supply. Therefore, trout have an obligatory need to produce lactate, either as a fuel for oxidative tissues and/or from organs relying on glycolysis. Exogenous lactate does not affect Ucrit or COT, probably because it acts as a substitute for glucose and lipids rather than extra fuel. We conclude that the observed 40% increase in Rd lactate is made possible by accelerating lactate entry into oxidative tissues via monocarboxylate transporters (MCTs). This observation together with the weak expression of MCTs and the phenomenon of white muscle lactate retention show that lactate metabolism of rainbow trout is significantly constrained by transmembrane transport. PMID:25121611

  15. Lactation and the Substance-Exposed Mother-Infant Dyad.

    PubMed

    Jansson, Lauren M; Velez, Martha

    2015-01-01

    Pregnant and postpartum women with substance use disorders have very unique needs and can present challenges to healthcare providers who are not familiar with how to evaluate and respond properly to their necessities. One such situation frequently arises when women with substance use disorders wish to breast-feed. There are many benefits and challenges to this practice that are specific to this population, and treating practitioners are often unclear on how to address them. The purpose of this article is to identify barriers to lactation in substance-exposed dyads and to provide strategies to mitigate these barriers and for promoting lactation in appropriate women with substance use disorders who wish to breast-feed.

  16. Innate immune signaling and gut-liver interactions in non-alcoholic fatty liver disease

    PubMed Central

    Trautwein, Christian

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and covers a disease spectrum ranging from steatosis to inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The innate immune response in the liver plays an important role during NAFLD progression. In addition, changes in the intestinal microbial balance and bacterial translocation can further affect disease progression. Immune cells in the liver recognize cell damage or pathogen invasion with intracellular or surface-expressed pattern recognition receptors (PRRs), subsequently initiating signaling cascades that trigger the release of factors promoting the inflammatory response during NAFLD progression. Therefore, mechanisms by which cells of the immune system are activated and recruited into the liver and how these cells cause injury and stress are important for understanding the inflammatory response during NAFLD. PMID:25568861

  17. Attribution of Blame for Wife Abuse by Alcoholics and Nonalcoholics.

    ERIC Educational Resources Information Center

    Carducci, Bernardo J.; McNeely, Judith A.

    Several researchers have explored the role of alcohol in domestic violence and attributions of blame. To compare the amount of blame attributed to an incident of wife abuse, alcoholic (N=52) and nonalcoholic (N=159) subjects read an account of wife abuse and distributed a percentage of the blame to the man, the woman, and the situation.…

  18. The Metabolic Syndrome and Its Influence on Nonalcoholic Steatohepatitis.

    PubMed

    Kanwar, Pushpjeet; Kowdley, Kris V

    2016-05-01

    Nonalcoholic steatohepatitis (NASH) and the metabolic syndrome (MetS) are highly prevalent in the Western population. Their pathogenesis is closely linked to insulin resistance, which serves as a therapeutic target for the management of these conditions. This review article reviews the research supporting the influence of MetS on NASH and includes studies supporting their similar epidemiology, pathogenesis, and treatment.

  19. Non-alcoholic fatty liver disease in children.

    PubMed

    Chaturvedi, Kanupriya; Vohra, Pankaj

    2012-09-01

    A cross sectional study was conducted in 100 children, aged 5 to 12 years, to find the prevalence of non-alcoholic fatty liver diseases (NAFLD), at New Delhi. Those with fatty liver on ultrasonography with no apparent etiology, were labeled as NAFLD. Three (3%) children had evidence of fatty liver on ultrasonography.

  20. INFLUENCE OF OXIDATIVE STRESS AND OBESITY IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS.

    PubMed

    Leghi, Gabriela Esteves; Domenici, Fernanda Aparecida; Vannucchi, Helio

    2015-01-01

    Nonalcoholic steatohepatitis is considered the hepatic manifestation of metabolic syndrome and it is particularly associated to the insulin resistance, hypertension, obesity and abnormalities in lipid and glucose metabolism. Considering the importance of obesity and oxidative stress in the pathophysiology of nonalcoholic steatohepatitis, this study aimed to evaluate the presence and association of the obesity and oxidative stress in this pathology. Fifteen outpatients with nonalcoholic steatohepatitis (nonalcoholic steatohepatitis group), diagnosed according to the histopathological findings from the liver biopsy, and 15 body mass index-matched subjects (non nonalcoholic steatohepatitis group) without nonalcoholic steatohepatitis were included. All volunteers were registered in a Brazilian University Hospital. Nutritional assessment (weight, height, body mass index and waist circumference) and biochemical analysis (fasting glucose, liver enzymes, lipid profile, leptin, superoxide dismutase, glutathione peroxidase, vitamins C and E, catalase and 8-isoprostane) were performed for all the participants. The student t test was used for statistical analysis, with P<0.05 as the significant factor. Nonalcoholic steatohepatitis patients had higher fasting glucose, hepatic enzymes (serum aspartate aminotransaminase, alanine aminotransaminase, gamma glutamyl transferase, alkaline phosphatase), triglycerides and superoxide dismutase and lower glutathione peroxidase values than non nonalcoholic steatohepatitis individuals. This paper demonstrates that only the presence of obesity is not enough to trigger alterations in all the studied biomarkers. Despite the majority of oxidative stress markers being found to be similar in both conditions, the nonalcoholic steatohepatitis subjects could be slightly more affected than the non nonalcoholic steatohepatitis individuals.

  1. 21 CFR 184.1639 - Potassium lactate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium lactate. 184.1639 Section 184.1639 Food... Specific Substances Affirmed as GRAS § 184.1639 Potassium lactate. (a) Potassium lactate (C3H5O3K, CAS Reg. No. 996-31-6) is the potassium salt of lactic acid. It is a hydroscopic, white, odorless solid and is...

  2. 21 CFR 184.1639 - Potassium lactate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium lactate. 184.1639 Section 184.1639 Food... Specific Substances Affirmed as GRAS § 184.1639 Potassium lactate. (a) Potassium lactate (C3H5O3K, CAS Reg. No. 996-31-6) is the potassium salt of lactic acid. It is a hydroscopic, white, odorless solid and is...

  3. 21 CFR 184.1639 - Potassium lactate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Potassium lactate. 184.1639 Section 184.1639 Food... GRAS § 184.1639 Potassium lactate. (a) Potassium lactate (C3H5O3K, CAS Reg. No. 996-31-6) is the potassium salt of lactic acid. It is a hydroscopic, white, odorless solid and is prepared commercially by...

  4. 21 CFR 184.1639 - Potassium lactate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium lactate. 184.1639 Section 184.1639 Food... Specific Substances Affirmed as GRAS § 184.1639 Potassium lactate. (a) Potassium lactate (C3H5O3K, CAS Reg. No. 996-31-6) is the potassium salt of lactic acid. It is a hydroscopic, white, odorless solid and is...

  5. 21 CFR 184.1639 - Potassium lactate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Potassium lactate. 184.1639 Section 184.1639 Food... Specific Substances Affirmed as GRAS § 184.1639 Potassium lactate. (a) Potassium lactate (C3H5O3K, CAS Reg. No. 996-31-6) is the potassium salt of lactic acid. It is a hydroscopic, white, odorless solid and is...

  6. 21 CFR 184.1768 - Sodium lactate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium lactate. 184.1768 Section 184.1768 Food and... Substances Affirmed as GRAS § 184.1768 Sodium lactate. (a) Sodium lactate (C3H5O3Na, CAS Reg. No. 72-17-3) is the sodium salt of lactic acid. It is prepared commercially by the neutralization of lactic acid...

  7. 21 CFR 184.1768 - Sodium lactate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Sodium lactate. 184.1768 Section 184.1768 Food and....1768 Sodium lactate. (a) Sodium lactate (C3H5O3Na, CAS Reg. No. 72-17-3) is the sodium salt of lactic acid. It is prepared commercially by the neutralization of lactic acid with sodium hydroxide. (b)...

  8. 21 CFR 184.1768 - Sodium lactate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium lactate. 184.1768 Section 184.1768 Food and... Substances Affirmed as GRAS § 184.1768 Sodium lactate. (a) Sodium lactate (C3H5O3Na, CAS Reg. No. 72-17-3) is the sodium salt of lactic acid. It is prepared commercially by the neutralization of lactic acid...

  9. 21 CFR 184.1768 - Sodium lactate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Sodium lactate. 184.1768 Section 184.1768 Food and... Substances Affirmed as GRAS § 184.1768 Sodium lactate. (a) Sodium lactate (C3H5O3Na, CAS Reg. No. 72-17-3) is the sodium salt of lactic acid. It is prepared commercially by the neutralization of lactic acid...

  10. 21 CFR 184.1768 - Sodium lactate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium lactate. 184.1768 Section 184.1768 Food and... Substances Affirmed as GRAS § 184.1768 Sodium lactate. (a) Sodium lactate (C3H5O3Na, CAS Reg. No. 72-17-3) is the sodium salt of lactic acid. It is prepared commercially by the neutralization of lactic acid...

  11. 21 CFR 184.1207 - Calcium lactate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Calcium lactate. 184.1207 Section 184.1207 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Specific Substances Affirmed as GRAS § 184.1207 Calcium lactate. (a) Calcium lactate (C6H10CaO6.xH2O,...

  12. 21 CFR 184.1207 - Calcium lactate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Calcium lactate. 184.1207 Section 184.1207 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Specific Substances Affirmed as GRAS § 184.1207 Calcium lactate. (a) Calcium lactate (C6H10CaO6.xH2O,...

  13. 21 CFR 184.1207 - Calcium lactate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium lactate. 184.1207 Section 184.1207 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1207 Calcium lactate. (a) Calcium lactate (C6H10CaO6.xH2O, where x is...

  14. 21 CFR 184.1207 - Calcium lactate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Calcium lactate. 184.1207 Section 184.1207 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DIRECT... GRAS § 184.1207 Calcium lactate. (a) Calcium lactate (C6H10CaO6.xH2O, where x is any integer up to...

  15. 21 CFR 184.1207 - Calcium lactate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Calcium lactate. 184.1207 Section 184.1207 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Specific Substances Affirmed as GRAS § 184.1207 Calcium lactate. (a) Calcium lactate (C6H10CaO6.xH2O,...

  16. Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease

    PubMed Central

    Miura, Kouichi; Ohnishi, Hirohide

    2014-01-01

    Emerging data have shown a close association between compositional changes in gut microbiota and the development of nonalcoholic fatty liver disease (NAFLD). The change in gut microbiota may alter nutritional absorption and storage. In addition, gut microbiota are a source of Toll-like receptor (TLR) ligands, and their compositional change can also increase the amount of TLR ligands delivered to the liver. TLR ligands can stimulate liver cells to produce proinflammatory cytokines. Therefore, the gut-liver axis has attracted much interest, particularly regarding the pathogenesis of NAFLD. The abundance of the major gut microbiota, including Firmicutes and Bacteroidetes, has been considered a potential underlying mechanism of obesity and NAFLD, but the role of these microbiota in NAFLD remains unknown. Several reports have demonstrated that certain gut microbiota are associated with the development of obesity and NAFLD. For instance, a decrease in Akkermansia muciniphila causes a thinner intestinal mucus layer and promotes gut permeability, which allows the leakage of bacterial components. Interventions to increase Akkermansia muciniphila improve the metabolic parameters in obesity and NAFLD. In children, the levels of Escherichia were significantly increased in nonalcoholic steatohepatitis (NASH) compared with those in obese control. Escherichia can produce ethanol, which promotes gut permeability. Thus, normalization of gut microbiota using probiotics or prebiotics is a promising treatment option for NAFLD. In addition, TLR signaling in the liver is activated, and its downstream molecules, such as proinflammatory cytokines, are increased in NAFLD. To data, TLR2, TLR4, TLR5, and TLR9 have been shown to be associated with the pathogenesis of NAFLD. Therefore, gut microbiota and TLRs are targets for NAFLD treatment. PMID:24966608

  17. Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease.

    PubMed

    Miura, Kouichi; Ohnishi, Hirohide

    2014-06-21

    Emerging data have shown a close association between compositional changes in gut microbiota and the development of nonalcoholic fatty liver disease (NAFLD). The change in gut microbiota may alter nutritional absorption and storage. In addition, gut microbiota are a source of Toll-like receptor (TLR) ligands, and their compositional change can also increase the amount of TLR ligands delivered to the liver. TLR ligands can stimulate liver cells to produce proinflammatory cytokines. Therefore, the gut-liver axis has attracted much interest, particularly regarding the pathogenesis of NAFLD. The abundance of the major gut microbiota, including Firmicutes and Bacteroidetes, has been considered a potential underlying mechanism of obesity and NAFLD, but the role of these microbiota in NAFLD remains unknown. Several reports have demonstrated that certain gut microbiota are associated with the development of obesity and NAFLD. For instance, a decrease in Akkermansia muciniphila causes a thinner intestinal mucus layer and promotes gut permeability, which allows the leakage of bacterial components. Interventions to increase Akkermansia muciniphila improve the metabolic parameters in obesity and NAFLD. In children, the levels of Escherichia were significantly increased in nonalcoholic steatohepatitis (NASH) compared with those in obese control. Escherichia can produce ethanol, which promotes gut permeability. Thus, normalization of gut microbiota using probiotics or prebiotics is a promising treatment option for NAFLD. In addition, TLR signaling in the liver is activated, and its downstream molecules, such as proinflammatory cytokines, are increased in NAFLD. To data, TLR2, TLR4, TLR5, and TLR9 have been shown to be associated with the pathogenesis of NAFLD. Therefore, gut microbiota and TLRs are targets for NAFLD treatment.

  18. Lactation--how important is it?

    PubMed

    MacIntyre, U E; Walker, A R

    1994-02-01

    In Africa, with poverty rising, and health care diminishing, a nutritional question is-what are the limits of successful physiological adaptation to low dietary intakes? In this review the practice of lactation is discussed, from both past and present viewpoints. Orthodox Recommended Allowances for lactation are scarcely ever met. Yet, through various adaptations, the huge majority of African and similarly placed mothers lactate successfully and produce milk of good quantity and quality. The benefits from supplements are discussed; broadly, results have been disappointing. Some good and adverse non-dietary practices are considered. Benefits for infant and mother from lactation, even for protracted periods, far exceed drawbacks.

  19. Hemichannel-mediated release of lactate.

    PubMed

    Karagiannis, Anastassios; Sylantyev, Sergiy; Hadjihambi, Anna; Hosford, Patrick S; Kasparov, Sergey; Gourine, Alexander V

    2016-07-01

    In the central nervous system lactate contributes to the extracellular pool of readily available energy substrates and may also function as a signaling molecule which mediates communication between glial cells and neurons. Monocarboxylate transporters are believed to provide the main pathway for lactate transport across the membranes. Here we tested the hypothesis that lactate could also be released via opening of pannexin and/or functional connexin hemichannels. In acute slices prepared from the brainstem, hippocampus, hypothalamus and cortex of adult rats, enzymatic amperometric biosensors detected significant tonic lactate release inhibited by compounds, which block pannexin/connexin hemichannels and facilitated by lowering extracellular [Ca(2+)] or increased PCO2 Enhanced lactate release triggered by hypoxia was reduced by ∼50% by either connexin or monocarboxylate transporter blockers. Stimulation of Schaffer collateral fibers triggered lactate release in CA1 area of the hippocampus, which was facilitated in conditions of low extracellular [Ca(2+)], markedly reduced by blockade of connexin hemichannels and abolished by lactate dehydrogenase inhibitor oxamate. These results indicate that lactate transport across the membranes may occur via mechanisms other than monocarboxylate transporters. In the central nervous system, hemichannels may function as a conduit of lactate release, and this mechanism is recruited during hypoxia and periods of enhanced neuronal activity. © The Author(s) 2015.

  20. Hemichannel-mediated release of lactate

    PubMed Central

    Karagiannis, Anastassios; Sylantyev, Sergiy; Hadjihambi, Anna; Hosford, Patrick S; Kasparov, Sergey

    2015-01-01

    In the central nervous system lactate contributes to the extracellular pool of readily available energy substrates and may also function as a signaling molecule which mediates communication between glial cells and neurons. Monocarboxylate transporters are believed to provide the main pathway for lactate transport across the membranes. Here we tested the hypothesis that lactate could also be released via opening of pannexin and/or functional connexin hemichannels. In acute slices prepared from the brainstem, hippocampus, hypothalamus and cortex of adult rats, enzymatic amperometric biosensors detected significant tonic lactate release inhibited by compounds, which block pannexin/connexin hemichannels and facilitated by lowering extracellular [Ca2+] or increased PCO2. Enhanced lactate release triggered by hypoxia was reduced by ∼50% by either connexin or monocarboxylate transporter blockers. Stimulation of Schaffer collateral fibers triggered lactate release in CA1 area of the hippocampus, which was facilitated in conditions of low extracellular [Ca2+], markedly reduced by blockade of connexin hemichannels and abolished by lactate dehydrogenase inhibitor oxamate. These results indicate that lactate transport across the membranes may occur via mechanisms other than monocarboxylate transporters. In the central nervous system, hemichannels may function as a conduit of lactate release, and this mechanism is recruited during hypoxia and periods of enhanced neuronal activity. PMID:26661210

  1. Non-alcoholic steatohepatitis in type 2 diabetes mellitus.

    PubMed

    Gupte, Parijat; Amarapurkar, Deepak; Agal, Subhash; Baijal, Rajiv; Kulshrestha, Pramod; Pramanik, Snehansu; Patel, Nikhil; Madan, Aruna; Amarapurkar, Anjali; Hafeezunnisa

    2004-08-01

    Non-alcoholic steatohepatitis (NASH) is commonly associated with type 2 diabetes mellitus (DM). Prevalence of NASH in type 2 DM has not been well studied and there is an epidemic rise in type 2 DM in Asian and Western populations. Its association with chronic liver disease in the form of NASH makes it an important health problem. Hence we have studied its prevalence and correlation of biochemical parameters with histological grades of non-alcoholic fatty liver disease (NAFLD) in otherwise asymptomatic type 2 DM patients. One hundred and forty-eight individuals were screened. Forty-eight individuals were excluded due to history of alcohol intake or liver disease as a result of other causes. One hundred non-alcoholic individuals with type 2 DM underwent abdominal ultrasonography (US abdomen). Forty-nine patients had evidence of fatty liver on US abdomen, and 32 of these 49 patients underwent liver biopsy. Four of 32 (12.5%) individuals had steatosis alone. Mild, moderate and severe NASH was present in 21/32 (65.5%), 4/32 (12.5%) and 3/32 (9.35%), respectively. Fibrosis was present in 7/32 (21.8%) patients (four grade 1 and three grade 3). There was no significant difference in body mass index (BMI), transaminase levels, serum cholesterol and triglyceride levels among patients with non-alcoholic fatty liver disease. We conclude that the prevalence of NASH is high in type 2 DM patients and liver biopsy is the only investigation to differentiate between non-alcoholic fatty liver and steatohepatitis.

  2. Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis

    PubMed Central

    Sanyal, Arun J.; Chalasani, Naga; Kowdley, Kris V.; McCullough, Arthur; Diehl, Anna Mae; Bass, Nathan M.; Neuschwander-Tetri, Brent A.; Lavine, Joel E.; Tonascia, James; Unalp, Aynur; Natta, Mark Van; Clark, Jeanne; Brunt, Elizabeth M.; Kleiner, David E.; Hoofnagle, Jay H.; Robuck, Patricia R.

    2010-01-01

    BACKGROUND Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrhosis. Currently, there is no established treatment for this disease. METHODS We randomly assigned 247 adults with nonalcoholic steatohepatitis and without diabetes to receive pioglitazone at a dose of 30 mg daily (80 subjects), vitamin E at a dose of 800 IU daily (84 subjects), or placebo (83 subjects), for 96 weeks. The primary outcome was an improvement in histologic features of nonalcoholic steatohepatitis, as assessed with the use of a composite of standardized scores for steatosis, lobular inflammation, hepatocellular ballooning, and fibrosis. Given the two planned primary comparisons, P values of less than 0.025 were considered to indicate statistical significance. RESULTS Vitamin E therapy, as compared with placebo, was associated with a significantly higher rate of improvement in nonalcoholic steatohepatitis (43% vs. 19%, P = 0.001), but the difference in the rate of improvement with pioglitazone as compared with placebo was not significant (34% and 19%, respectively; P = 0.04). Serum alanine and aspartate aminotransferase levels were reduced with vitamin E and with pioglitazone, as compared with placebo (P<0.001 for both comparisons), and both agents were associated with reductions in hepatic steatosis (P = 0.005 for vitamin E and P<0.001 for pioglitazone) and lobular inflammation (P = 0.02 for vitamin E and P = 0.004 for pioglitazone) but not with improvement in fibrosis scores (P = 0.24 for vitamin E and P = 0.12 for pioglitazone). Subjects who received pioglitazone gained more weight than did those who received vitamin E or placebo; the rates of other side effects were similar among the three groups. CONCLUSIONS Vitamin E was superior to placebo for the treatment of nonalcoholic steatohepatitis in adults without diabetes. There was no benefit of pioglitazone over placebo for the primary outcome; however, significant benefits of pioglitazone were observed for some

  3. Lactate Sensors on Flexible Substrates

    PubMed Central

    Yang, Xuesong; Fu, Timothy; Kota, Pavan Kumar; Tjia, Maggie; Nguyen, Cuong Manh; Chiao, Jung-Chih

    2016-01-01

    Lactate detection by an in situ sensor is of great need in clinical medicine, food processing, and athletic performance monitoring. In this paper, a flexible, easy to fabricate, and low-cost biosensor base on lactate oxidase is presented. The fabrication processes, including metal deposition, sol-gel IrOx deposition, and drop-dry enzyme loading method, are described in detail. The loaded enzyme was examined by scanning electron microscopy. Cyclic voltammetry was used to characterize the sensors. Durability, sensibility, and selectivity of the biosensors were examined. The comparison for different electrode sizes and different sensing film materials was conducted. The sensor could last for four weeks with an average surface area normalized sensitivity of 950 nA/(cm2 mM) and 9250 nA/(cm2 mM) for Au-based electrodes, and IrOx-modified electrodes respectively, both with an electrode size of 100 × 50 μm. The self-referencing method to record noises simultaneously with the working electrode greatly improved sensor sensitivity and selectivity. The sensor showed little response to interference chemicals, such as glutamate and dopamine. PMID:27657147

  4. Breastfeeding practices and lactation mastitis.

    PubMed

    Foxman, B; Schwartz, K; Looman, S J

    1994-03-01

    Clinical impression suggests that lactation mastitis is associated with inexperienced nursers, improper nursing techniques, stress and fatigue. A pilot study was conducted to describe the frequency of self-reported breastfeeding practices during the first week post partum among 100 breastfeeding women delivering at a freestanding birthing center or participating in an early discharge program. Nine cases of lactation mastitis were identified from the survey population and an additional 8 from the target population for the survey. Seventeen controls matched by delivery date were identified from survey participants. The frequency of self-reported breastfeeding practices, the presence of fatigue and stress during the week prior to the mastitis date in the case was compared among cases and controls. In the first week post partum, most women fed their babies every 2-3 hr for approx. 20 min a feeding. The cradle or Madonna position was the most frequently used nursing position. Nine percent reported supplementing feedings with formula. Women with mastitis were more likely than controls to report a history of mastitis with a previous child. In the week prior to the mastitis date of the case, women with mastitis were more likely than controls to report breast or nipple pain and cracks or breast fissures. They were less likely to report being able to take a daytime nap. Future studies should focus on the relative importance of and interrelationships among these factors.

  5. Alcoholic and non-alcoholic steatohepatitis.

    PubMed

    Neuman, Manuela G; French, Samuel W; French, Barbara A; Seitz, Helmut K; Cohen, Lawrence B; Mueller, Sebastian; Osna, Natalia A; Kharbanda, Kusum K; Seth, Devanshi; Bautista, Abraham; Thompson, Kyle J; McKillop, Iain H; Kirpich, Irina A; McClain, Craig J; Bataller, Ramon; Nanau, Radu M; Voiculescu, Mihai; Opris, Mihai; Shen, Hong; Tillman, Brittany; Li, Jun; Liu, Hui; Thomes, Paul G; Ganesan, Murali; Malnick, Steve

    2014-12-01

    This paper is based upon the "Charles Lieber Satellite Symposia" organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human immunodeficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible

  6. Alcoholic and non-alcoholic steatohepatitis

    PubMed Central

    Neuman, Manuela G.; French, Samuel W.; French, Barbara A.; Seitz, Helmut K.; Cohen, Lawrence B.; Mueller, Sebastian; Osna, Natalia A.; Kharbanda, Kusum K.; Seth, Devanshi; Bautista, Abraham; Thompson, Kyle J.; McKillop, Iain H.; Kirpich, Irina A.; McClain, Craig J.; Bataller, Ramon; Nanau, Radu M.; Voiculescu, Mihai; Opris, Mihai; Shen, Hong; Tillman, Brittany; Li, Jun; Liu, Hui; Thomas, Paul G.; Ganesan, Murali; Malnick, Steve

    2015-01-01

    This paper is based upon the “Charles Lieber Satellite Symposia” organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its comorbidities with chronic viral hepatitis in the presence or absence of human deficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible

  7. Review article: Drug therapy for non-alcoholic fatty liver disease.

    PubMed

    Comar, K M; Sterling, R K

    2006-01-15

    Non-alcoholic fatty liver disease represents a spectrum of liver diseases, characterized mainly by macrovesicular steatosis in the absence of significant alcohol ingestion. Non-alcoholic fatty liver disease includes both non-alcoholic fatty liver and non-alcoholic steatohepatitis. Non-alcoholic steatohepatitis once considered a benign process is now known to lead to progressive fibrosis and cirrhosis. Histologically indistinguishable from alcoholic liver disease, the exact aetiology of non-alcoholic fatty liver disease remains unknown, but the fundamental pathophysiological process appears to be insulin resistance and oxidative stress related to the metabolic syndrome. Therapy has focused on risk factors, weight reduction and pharmacological intervention. Promising pharmacological treatments have been demonstrated with antioxidants, insulin sensitizers, hepatoprotectants and lipid-lowering agents. However, without larger randomized studies, no pharmacological treatments can be recommended at this time.

  8. Lactate and glucose interactions during rest and exercise in men: effect of exogenous lactate infusion.

    PubMed

    Miller, Benjamin F; Fattor, Jill A; Jacobs, Kevin A; Horning, Michael A; Navazio, Franco; Lindinger, Michael I; Brooks, George A

    2002-11-01

    To test the hypothesis that lactate plays a central role in the distribution of carbohydrate (CHO) potential energy for oxidation and glucose production (GP), we performed a lactate clamp (LC) procedure during rest and moderate intensity exercise. Blood [lactate] was clamped at approximately 4 mM by exogenous lactate infusion. Subjects performed 90 min exercise trials at 65 % of the peak rate of oxygen consumption (V(O(2))(,peak); 65 %), 55 % V(O(2))(,peak) (55 %) and 55 % V(O(2))(,peak) with lactate clamped to the blood [lactate] that was measured at 65 % V(O(2))(,peak) (55 %-LC). Lactate and glucose rates of appearance (R(a)), disappearance (R(d)) and oxidation (R(ox)) were measured with a combination of [3-(13)C]lactate, H(13)CO(3)(-), and [6,6-(2)H(2)]glucose tracers. During rest and exercise, lactate R(a) and R(d) were increased at 55 %-LC compared to 55 %. Glucose R(a) and R(d) were decreased during 55 %-LC compared to 55 %. Lactate R(ox) was increased by LC during exercise (55 %: 6.52 +/- 0.65 and 55 %-LC: 10.01 +/- 0.68 mg kg(-1) min(-1)) which was concurrent with a decrease in glucose oxidation (55 %: 7.64 +/- 0.4 and 55 %-LC: 4.35 +/- 0.31 mg kg(-1) min(-1)). With LC, incorporation of (13)C from tracer lactate into blood glucose (L GNG) increased while both GP and calculated hepatic glycogenolysis (GLY) decreased. Therefore, increased blood [lactate] during moderate intensity exercise increased lactate oxidation, spared blood glucose and decreased glucose production. Further, exogenous lactate infusion did not affect rating of perceived exertion (RPE) during exercise. These results demonstrate that lactate is a useful carbohydrate in times of increased energy demand.

  9. Recent advances in understanding the role of adipocytokines during non-alcoholic fatty liver disease pathogenesis and their link with hepatokines.

    PubMed

    Panera, Nadia; Della Corte, Claudia; Crudele, Annalisa; Stronati, Laura; Nobili, Valerio; Alisi, Anna

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is currently considered the main cause of chronic liver disease worldwide. Mechanisms leading to the development and progression of this disease are topics of great interest for researchers and clinicians. The current multi-hit hypothesis has thrown the crosstalk between liver and adipose tissue into sharp focus. It is well known that adipose tissue produces circulating factors, known as adipocytokines, which exert several effects on liver cells, promoting the onset of NAFLD and its progression to non-alcoholic steatohepatitis in obese subjects. In a similar way, hepatocytes may also respond to obesogenic stimuli by producing and releasing hepatokines into the circulation. Here, the authors provide an overview of recent advances in our understanding of the role of the most relevant adipocytokines and hepatokines in NAFLD pathogenesis, highlighting their possible molecular and functional interactions.

  10. Lactate oxidation in human skeletal muscle mitochondria.

    PubMed

    Jacobs, Robert A; Meinild, Anne-Kristine; Nordsborg, Nikolai B; Lundby, Carsten

    2013-04-01

    Lactate is an important intermediate metabolite in human bioenergetics and is oxidized in many different tissues including the heart, brain, kidney, adipose tissue, liver, and skeletal muscle. The mechanism(s) explaining the metabolism of lactate in these tissues, however, remains unclear. Here, we analyze the ability of skeletal muscle to respire lactate by using an in situ mitochondrial preparation that leaves the native tubular reticulum and subcellular interactions of the organelle unaltered. Skeletal muscle biopsies were obtained from vastus lateralis muscle in 16 human subjects. Samples were chemically permeabilized with saponin, which selectively perforates the sarcolemma and facilitates the loss of cytosolic content without altering mitochondrial membranes, structure, and subcellular interactions. High-resolution respirometry was performed on permeabilized muscle biopsy preparations. By use of four separate and specific substrate titration protocols, the respirometric analysis revealed that mitochondria were capable of oxidizing lactate in the absence of exogenous LDH. The titration of lactate and NAD(+) into the respiration medium stimulated respiration (P ≤ 0.003). The addition of exogenous LDH failed to increase lactate-stimulated respiration (P = 1.0). The results further demonstrate that human skeletal muscle mitochondria cannot directly oxidize lactate within the mitochondrial matrix. Alternately, these data support previous claims that lactate is converted to pyruvate within the mitochondrial intermembrane space with the pyruvate subsequently taken into the mitochondrial matrix where it enters the TCA cycle and is ultimately oxidized.

  11. Possible mechanisms for lactate's induction of panic.

    PubMed

    Liebowitz, M R; Gorman, J M; Fyer, A; Dillon, D; Levitt, M; Klein, D F

    1986-04-01

    Forty-three patients with panic disorder or agoraphobia with panic attacks and 20 control subjects received 0.5 M racemic sodium lactate intravenous infusions, single-blind as to duration and sequence. During the procedure, pulse; blood pressure; blood L-lactate and pyruvate; plasma ionized calcium, phosphate, prolactin, epinephrine, norepinephrine, and cortisol levels; and venous PCO2, pH, and bicarbonate were measured in an attempt to clarify the mechanism of lactate-induced panic attacks. During the infusion, 72% of the patients but none of the control subjects had panic attacks. The laboratory findings suggest that peripheral catecholamine surge is not the mechanism by which lactate causes panic, although elevated epinephrine may be a predisposing factor. Heightened central noradrenergic activity was present in many but not all of the attacks. Contrary to previous hypotheses, neither depression of ionized calcium nor induction of metabolic alkalosis appears sufficient to cause panic during lactate infusion.

  12. Pathophysiological mechanisms involved in non-alcoholic steatohepatitis and novel potential therapeutic targets

    PubMed Central

    Higuera-de la Tijera, Fátima; Servín-Caamaño, Alfredo I

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a major health care problem and represents the hepatic expression of the metabolic syndrome. NAFLD is classified as non-alcoholic fatty liver (NAFL) or simple steatosis, and non-alcoholic steatohepatitis (NASH). NASH is characterized by the presence of steatosis and inflammation with or without fibrosis. The physiopathology of NAFL and NASH and their progression to cirrhosis involve several parallel and interrelated mechanisms, such as, insulin resistance (IR), lipotoxicity, inflammation, oxidative stress, and recently the gut-liver axis interaction has been described. Incretin-based therapies could play a role in the treatment of NAFLD. Glucagon-like peptide-1 (GLP-1) is an intestinal mucosa-derived hormone which is secreted into the bloodstream in response to nutrient ingestion; it favors glucose-stimulated insulin secretion, inhibition of postprandial glucagon secretion and delayed gastric emptying. It also promotes weight loss and is involved in lipid metabolism. Once secreted, GLP-1 is quickly degraded by dipeptidyl peptidase-4 (DPP-4). Therefore, DPP-4 inhibitors are able to extend the activity of GLP-1. Currently, GLP-1 agonists and DPP-4 inhibitors represent attractive options for the treatment of NAFLD and NASH. The modulation of lipid and glucose metabolism through nuclear receptors, such as the farsenoid X receptor, also constitutes an attractive therapeutic target. Obeticholic acid is a potent activator of the farnesoid X nuclear receptor and reduces liver fat content and fibrosis in animal models. Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid with immunomodulatory, anti-inflammatory, antiapoptotic, antioxidant and anti-fibrotic properties. UDCA can improve IR and modulate lipid metabolism through its interaction with nuclear receptors such as, TGR5, farnesoid X receptor-α, or the small heterodimeric partner. Finally, pharmacologic modulation of the gut microbiota could have a role in the therapy of

  13. Discrimination of Nonalcoholic Steatohepatitis Using Transient Elastography in Patients with Nonalcoholic Fatty Liver Disease

    PubMed Central

    Kim, Seung Up; Jang, Jae Young; Park, Hana; Kim, Ja Kyung; Lee, Chun Kyon; Chon, Young Eun; Han, Kwang-Hyub

    2016-01-01

    Background/aims The accuracy of noninvasive markers to discriminate nonalcoholic steatohepatitis (NASH) is unsatisfactory. We investigated whether transient elastography (TE) could discriminate patients with NASH from those with nonalcoholic fatty liver disease (NAFLD). Methods The patients suspected of NAFLD who underwent liver biopsy and concomitant TE were recruited from five tertiary centers between November 2011 and December 2013. Results The study population (n = 183) exhibited a mean age of 40.6 years and male predominance (n = 111, 60.7%). Of the study participants, 89 (48.6%) had non-NASH and 94 (51.4%) had NASH. The controlled attenuation parameter (CAP) and liver stiffness (LS) were significantly correlated with the degrees of steatosis (r = 0.656, P<0.001) and fibrosis (r = 0.714, P<0.001), respectively. The optimal cut-off values for steatosis were 247 dB/m for S1, 280 dB/m for S2, and 300 dB/m for S3. Based on the independent predictors derived from multivariate analysis [P = 0.044, odds ratio (OR) 4.133, 95% confidence interval (CI) 1.037–16.470 for CAP>250 dB/m; P = 0.013, OR 3.399, 95% CI 1.295–8.291 for LS>7.0 kPa; and P<0.001, OR 7.557, 95% CI 2.997–19.059 for Alanine aminotransferase>60 IU/L], we developed a novel CLA model for discriminating patients with NASH. The CLA model showed good discriminatory capability, with an area under the receiver operating characteristic curve (AUROC) of 0.812 (95% CI 0.724–0.880). To assess discriminatory power, the AUROCs, as determined by the bootstrap method, remained largely unchanged between iterations, with an average value of 0.833 (95% CI 0.740–0.893). Conclusion This novel TE-based CLA model showed acceptable accuracy in discriminating NASH from simple steatosis. However, further studies are required for external validation. PMID:27284700

  14. A20 Attenuates FFAs-induced Lipid Accumulation in Nonalcoholic Steatohepatitis

    PubMed Central

    Ai, Luoyan; Xu, Qingqing; Wu, Changwei; Wang, Xiaohan; Chen, Zhiwei; Su, Dazhi; Jiang, Xiaoke; Xu, Antao; Lin, Qing; Fan, Zhuping

    2015-01-01

    A20 is a ubiquitin-editing enzyme that attenuates the activity of proximal signaling complexes at pro-inflammatory receptors. It has been well documented that A20 protein plays an important role in response to liver injury and hepatocytes apoptosis in pro-inflammatory pathways. However, there was little evidence showing that A20 protein was involving in fatty-acid homeostasis except the up-regulation of two fatty acid metabolism regulatory genes at mRNA level (PPARa and CPT1a) by adenovirus-mediated A20 protein overexpression. In this study we found that: 1) the expression level of A20 protein was significantly higher in the steatotic liver from MCD-fed mice than the controls; 2) Overexpression of A20 protein suppressed FFAs-stimulated triglyceride deposition in HepG2 cells while under expression of A20 protein increased FFAs-stimulated triglyceride deposition; 3) Overexpression of A20 protein in HepG2 cells upregulated genes that promote β-oxidation and decreased the mRNA levels of key lipogenic genes such as fatty acid synthase (FAS), indicating A20 function as anti-steatotic factor by the activation of mitochondrial β-oxidation and attenuation of de novo lipogenesis; 4) Nonalcoholic steatohepatitis (NASH) patients showed significantly higher A20 expression level in liver compared with control individuals. Our results demonstrated that A20 protein plays an important role in fatty-acid homeostasis in human as well as animals. In addition, our data suggested that the pathological function of A20 protein in hepatocyte from lipotoxicity to NASH is by the alleviation of triglyceride accumulation in hepatocytes. Elevated expression of A20 protein could be a potential therapeutic strategy for preventing the progression of nonalcoholic steatohepatitis. PMID:26681923

  15. Systematic Review: Nutrition and Physical Activity in the Management of Paediatric Nonalcoholic Fatty Liver Disease.

    PubMed

    Gibson, Philippa S; Lang, Sarah; Dhawan, Anil; Fitzpatrick, Emer; Blumfield, Michelle L; Truby, Helen; Hart, Kathryn H; Moore, J Bernadette

    2017-08-01

    The aim of the study was to evaluate efficacy of nutrition and physical activity interventions in the clinical management of paediatric nonalcoholic fatty liver disease. The prevalence of paediatric nonalcoholic fatty liver disease continues to rise alongside childhood obesity. Weight loss through lifestyle modification is currently first-line treatment, although supplementation of specific dietary components may be beneficial. Medline, CINAHL, EMBASE, Scopus, and Cochrane Libraries were systematically searched to identify randomized controlled trials assessing nutritional and physical activity interventions. Primary outcome measures were changes to liver biomarkers assessed by imaging, histology, or serum liver function tests. Study quality was evaluated using the American Dietetic Association Quality Criteria Checklist. Fifteen articles met eligibility criteria investigating nutritional supplementation (vitamin E [n = 6], probiotics [n = 2], omega-3 fatty acids [n = 5]), dietary modification (low glycaemic load [n = 1] and reducing fructose intake [n = 1]). No randomized controlled trials examining physical activity interventions were identified. Vitamin E was ineffective at improving alanine transaminase levels, whereas omega-3 fatty acids decreased hepatic fat content. Probiotics gave mixed results, whereas reduced fructose consumption did not improve primary outcome measures. A low glycaemic load diet and a low-fat diet appeared equally effective in decreasing hepatic fat content and transaminases. Most studies were deemed neutral as assessed by the American Dietetic Association Quality Criteria Checklist. The limited evidence base inhibits the prescription of specific dietary and/or lifestyle strategies for clinical practice. General healthy eating and physical activity guidelines, promoting weight loss, should remain first-line treatment until high-quality evidence emerges that support specific interventions that offer additional clinical

  16. Involvement of the TAGE-RAGE system in non-alcoholic steatohepatitis: Novel treatment strategies

    PubMed Central

    Takeuchi, Masayoshi; Takino, Jun-ichi; Sakasai-Sakai, Akiko; Takata, Takanobu; Ueda, Tadashi; Tsutsumi, Mikihiro; Hyogo, Hideyuki; Yamagishi, Sho-ichi

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease around the world. It includes a spectrum of conditions from simple steatosis to non-alcoholic steatohepatitis (NASH) and can lead to fibrosis, cirrhosis, liver failure, and/or hepatocellular carcinoma. NAFLD is also associated with other medical conditions such as obesity, diabetes mellitus (DM), metabolic syndrome, hypertension, insulin resistance, hyperlipidemia, and cardiovascular disease (CVD). In diabetes, chronic hyperglycemia contributes to the development of both macro- and microvascular conditions through a variety of metabolic pathways. Thus, it can cause a variety of metabolic and hemodynamic conditions, including upregulated advanced glycation end-products (AGEs) synthesis. In our previous study, the most abundant type of toxic AGEs (TAGE); i.e., glyceraldehyde-derived AGEs, were found to make a significant contribution to the pathogenesis of DM-induced angiopathy. Furthermore, accumulating evidence suggests that the binding of TAGE with their receptor (RAGE) induces oxidative damage, promotes inflammation, and causes changes in intracellular signaling and the expression levels of certain genes in various cell populations including hepatocytes and hepatic stellate cells. All of these effects could facilitate the pathogenesis of hypertension, cancer, diabetic vascular complications, CVD, dementia, and NASH. Thus, inhibiting TAGE synthesis, preventing TAGE from binding to RAGE, and downregulating RAGE expression and/or the expression of associated effector molecules all have potential as therapeutic strategies against NASH. Here, we examine the contributions of RAGE and TAGE to various conditions and novel treatments that target them in order to prevent the development and/or progression of NASH. PMID:25544875

  17. Effect of intracellular lipid accumulation in a new model of non-alcoholic fatty liver disease

    PubMed Central

    2012-01-01

    Background In vitro exposure of liver cells to high concentrations of free fatty acids (FFA) results in fat overload which promotes inflammatory and fibrogenic response similar to those observed in patients with Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH). Since the mechanisms of this event have not been fully characterized, we aimed to analyze the fibrogenic stimuli in a new in vitro model of NASH. Methods HuH7 cells were cultured for 24 h in an enriched medium containing bovine serum albumin and increasing concentrations of palmitic and oleic acid at a molar ratio of 1:2 (palmitic and oleic acid, respectively). Cytotoxic effect, apoptosis, oxidative stress, and production of inflammatory and fibrogenic cytokines were measured. Results FFA induces a significant increment in the intracellular content of lipid droplets. The gene expression of interleukin-6, interleukin-8 and tumor necrosis factor alpha was significantly increased. The protein level of interleukin-8 was also increased. Intracellular lipid accumulation was associated to a significant up-regulation in the gene expression of transforming growth factor beta 1, alpha 2 macroglobulin, vascular endothelial growth factor A, connective tissue growth factor, insulin-like growth factor 2, thrombospondin 1. Flow cytometry analysis demonstrated a significant increment of early apoptosis and production of reactive oxygen species. Conclusions The exposure of hepatocytes to fatty acids elicits inflammation, increase of oxidative stress, apoptosis and production of fibrogenic cytokines. These data support a primary role of FFA in the pathogenesis of NAFLD and NASH. PMID:22380754

  18. Non-alcoholic fatty liver disease and obesity: biochemical, metabolic and clinical presentations.

    PubMed

    Milić, Sandra; Lulić, Davorka; Štimac, Davor

    2014-07-28

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components. Up to 80% of patients with NAFLD are obese, defined as a body mass index (BMI) > 30 kg/m(2). However, the distribution of fat tissue plays a greater role in insulin resistance than the BMI. The large amount of visceral adipose tissue (VAT) in morbidly obese (BMI > 40 kg/m(2)) individuals contributes to a high prevalence of NAFLD. Free fatty acids derived from VAT tissue, as well as from dietary sources and de novo lipogenesis, are released to the portal venous system. Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD. In addition, secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways, which are also activated by free fatty acids, and contribute to insulin resistance. Most NAFLD patients are asymptomatic on clinical presentation, even though some may present with fatigue, dyspepsia, dull pain in the liver and hepatosplenomegaly. Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications, anti-obesity medication and bariatric surgery. This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease. The relative contribution of visceral and liver fat to insulin resistance is discussed, and recommendations for clinical evaluation of affected individuals is provided.

  19. Hepatic reticuloendothelial system cell iron deposition is associated with increased apoptosis in nonalcoholic fatty liver disease.

    PubMed

    Maliken, Bryan D; Nelson, James E; Klintworth, Heather M; Beauchamp, Mary; Yeh, Matthew M; Kowdley, Kris V

    2013-05-01

    The aim of this study was to examine the relationship between the presence of hepatic iron deposition, apoptosis, histologic features, and serum markers of oxidative stress (OS) and cell death in nonalcoholic fatty liver disease (NAFLD). Clinical, biochemical, metabolic, and independent histopathologic assessment was conducted in 83 unselected patients with biopsy-proven NAFLD from a single center. Apoptosis and necrosis in serum was quantified using serum cytokeratin 18 (CK18) M30 and M65 enzyme-linked immunosorbent assays and in liver by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining in situ. Serum malondialdehyde (MDA) and thioredoxin-1 (Trx1) levels were measured to evaluate OS. Presence of reticuloendothelial system (RES) cell iron in the liver was associated with nonalcoholic steatohepatitis (P < 0.05) and increased hepatic TUNEL staining (P = 0.02), as well as increased serum levels of apoptosis-specific (M30; P = 0.013) and total (M65; P = 0.006) CK18 fragments, higher MDA (P = 0.002) and lower antioxidant Trx1 levels (P = 0.012), compared to patients without stainable hepatic iron. NAFLD patients with a hepatocellular (HC) iron staining pattern also had increased serum MDA (P = 0.006), but not M30 CK18 levels or TUNEL staining, compared to subjects without stainable hepatic iron. Patients with iron deposition limited to hepatocytes had a lower proportion of apoptosis-specific M30 fragments relative to total M65 CK18 levels (37% versus ≤25%; P < 0.05). Presence of iron in liver RES cells is associated with NASH, increased apoptosis, and increased OS. HC iron deposition in NAFLD is also associated with OS and may promote hepatocyte necrosis in this disease. Copyright © 2013 American Association for the Study of Liver Diseases.

  20. Metabolic syndrome in childhood from impaired carbohydrate metabolism to nonalcoholic fatty liver disease.

    PubMed

    Manco, Melania

    2011-10-01

    Compelling evidence supports the concept that nonalcoholic fatty liver disease (NAFLD) represents the hepatic component of metabolic syndrome (MetS). Intrahepatic fat seems to predict more strongly than does visceral adiposity an individual's cardiovascular risk and the likelihood that metabolic abnormalities are present in youth. Young individuals with fatty liver are more insulin resistant and present with a higher prevalence of metabolic abnormalities than do individuals without intrahepatic fat accumulation. They also present with a certain endothelial dysfunction and greater carotid intima-media thickness. Conversely, youth with MetS seem to have an increased risk of developing liver inflammation, a condition termed nonalcoholic steatohepatitis (NASH), and fibrosis. In the context of MetS, the liver is central in that it can drive both hepatic and systemic insulin resistance, trigger low-grade inflammation, and promote atherogenic processes. In the context of MetS, NAFLD and altered carbohydrate metabolism track from childhood to adulthood. Thus, prevention, recognition, and effective treatment of these two abnormalities may limit the burden of morbidity and mortality associated with obesity and may delay onset of cardiovascular disease in early adulthood. The present review aims at systematically presenting evidence of the critical interplay of fatty liver and altered glucose metabolism in youth. It attempts to provide pathogenetic explanations for such an association and the rationale for its treatment, with particular regard to nutritional interventions. Key teaching points: Overweight and obese youth should be screened for fatty liver disease once after puberty by liver function tests and ultrasonography. Screening for fatty liver should be accurately performed in young patients with features of metabolic syndrome. Obese patients with fatty liver are at increased risk for altered glucose metabolism, thus they should undergo an oral glucose tolerance test

  1. Inhibition of stress mediated cell death by human lactate dehydrogenase B in yeast.

    PubMed

    Sheibani, Sara; Jones, Natalie K; Eid, Rawan; Gharib, Nada; Arab, Nagla T T; Titorenko, Vladimir; Vali, Hojatollah; Young, Paul A; Greenwood, Michael T

    2015-08-01

    We report the identification of human L- lactate dehydrogenase B (LDHB) as a novel Bax suppressor. Yeast heterologously expressing LDHB is also resistant to the lethal effects of copper indicating that it is a general suppressor of stress mediated cell death. To identify potential LDHB targets, LDHB was expressed in yeast mutants defective in apoptosis, necrosis and autophagy. The absence of functional PCD regulators including MCA1, YBH3, cyclophilin (CPR3) and VMA3, as well as the absence of the pro-survival autophagic pathway (ATG1,7) did not interfere with the LDHB mediated protection against copper indicating that LDHB functions independently of known PCD regulators or by simply blocking or stimulating a common PCD promoting or inhibitory pathway. Measurements of lactate levels revealed that short-term copper stress (1.6 mM, 4 h), does not increase intracellular levels of lactate, instead a three-fold increase in extracellular lactate was observed. Thus, yeast cells resemble mammalian cells where different stresses are known to lead to increased lactate production leading to lactic acidosis. In agreement with this, we found that the addition of exogenous lactic acid to growth media was sufficient to induce cell death that could be inhibited by the expression of LDHB. Taken together our results suggest that lactate dehydrogenase is a general suppressor of PCD in yeast. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming

    PubMed Central

    Civini, Sara; Pacelli, Consiglia; Dieng, Mame Massar; Lemieux, William; Jin, Ping; Bazin, Renée; Patey, Natacha; Marincola, Francesco M.; Moldovan, Florina; Zaouter, Charlotte; Trudeau, Louis-Eric; Benabdhalla, Basma; Louis, Isabelle; Beauséjour, Christian; Stroncek, David; Le Deist, Françoise; Haddad, Elie

    2016-01-01

    Human mesenchymal stromal cells (MSC) have been shown to dampen immune response and promote tissue repair, but the underlying mechanisms are still under investigation. Herein, we demonstrate that umbilical cord-derived MSC (UC-MSC) alter the phenotype and function of monocyte-derived dendritic cells (DC) through lactate-mediated metabolic reprogramming. UC-MSC can secrete large quantities of lactate and, when present during monocyte-to-DC differentiation, induce instead the acquisition of M2-macrophage features in terms of morphology, surface markers, migratory properties and antigen presentation capacity. Microarray expression profiling indicates that UC-MSC modify the expression of metabolic-related genes and induce a M2-macrophage expression signature. Importantly, monocyte-derived DC obtained in presence of UC-MSC, polarize naïve allogeneic CD4+ T-cells into Th2 cells. Treatment of UC-MSC with an inhibitor of lactate dehydrogenase strongly decreases lactate concentration in culture supernatant and abrogates the effect on monocyte-to-DC differentiation. Metabolic analysis further revealed that UC-MSC decrease oxidative phosphorylation in differentiating monocytes while strongly increasing the spare respiratory capacity proportional to the amount of secreted lactate. Because both MSC and monocytes are recruited in vivo at the site of tissue damage and inflammation, we propose the local increase of lactate concentration induced by UC-MSC and the consequent enrichment in M2-macrophage generation as a mechanism to achieve immunomodulation. PMID:27070086

  3. L-Lactate Protects Skin Fibroblasts against Aging-Associated Mitochondrial Dysfunction via Mitohormesis.

    PubMed

    Zelenka, Jaroslav; Dvořák, Aleš; Alán, Lukáš

    2015-01-01

    A moderate elevation of reactive oxygen species (ROS) production and a mild inhibition of mitochondrial respiratory chain have been associated with a health promotion and a lifespan extension in several animal models of aging. Here, we tested whether this phenomenon called mitohormesis could be mediated by L-lactate. The treatment with 5 mM L-lactate significantly increased H2O2 production and slightly inhibited the respiration in cultured skin fibroblasts and in isolated mitochondria. The L-lactate exposure was associated with oxidation of intracellular glutathione, phosphorylation of 5'AMP-activated protein kinase (AMPK), and induction of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) transcription. A replicative aging of fibroblasts (L0) with a constant (LC), or intermittent 5 mM L-lactate (LI) in media showed that the high-passage LI fibroblasts have higher respiration, lower H2O2 release, and lower secretion of L-lactate compared to L0 and LC. This protection against mitochondrial dysfunction in LI cells was associated with lower activity of mechanistic target of rapamycin complex 1 (mTORC1), less signs of cellular senescence, and increased autophagy compared to L0 and LC. In conclusion, we demonstrated that intermittent but not constant exposure to L-lactate triggers mitohormesis, prevents aging-associated mitochondrial dysfunction, and improves other markers of aging.

  4. Lactate accumulation following isometric exercise training and its relationship with reduced resting blood pressure.

    PubMed

    Devereux, Gavin R; Coleman, Damian; Wiles, Jonathan D; Swaine, Ian

    2012-01-01

    The purpose of this study was (a) to assess lactate accumulation during isometric exercise, and to quantify the shifts in accumulation following isometric training; and (b) to relate any training-induced changes in lactate accumulation to reductions in resting blood pressure. Eleven male participants undertook isometric training for a 4-week period using bilateral-leg exercise. Training caused reductions in systolic, diastolic, and mean arterial resting blood pressure (of -4.9 ± 6.3 mmHg, P = 0.01; -2.6 ± 3.0 mmHg, P = 0.01; and -2.6 ± 2.3 mmHg, P = 0.001 respectively; mean ± s). These were accompanied by changes in muscle activity, taken as electromyographic activity to reach a given lactate concentration (from 114 ± 22 to 131 ± 27 mV and from 136 ± 25 to 155 ± 34 mV for 3 and 4 mmol · L(-1) respectively. Training intensity expressed relative to peak lactate was correlated with reduced resting systolic and mean arterial blood pressure. Training caused significant shifts in lactate accumulation, and reductions in resting blood pressure are strongly related to training intensity, when expressed relative to pre-training peak lactate. This suggests that higher levels of local muscle anaerobiosis may promote the training-induced reductions in resting blood pressure.

  5. Role of Mitochondria in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Nassir, Fatiha; Ibdah, Jamal A.

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) affects about 30% of the general population in the United States and includes a spectrum of disease that includes simple steatosis, non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. Significant insight has been gained into our understanding of the pathogenesis of NALFD; however the key metabolic aberrations underlying lipid accumulation in hepatocytes and the progression of NAFLD remain to be elucidated. Accumulating and emerging evidence indicate that hepatic mitochondria play a critical role in the development and pathogenesis of steatosis and NAFLD. Here, we review studies that document a link between the pathogenesis of NAFLD and hepatic mitochondrial dysfunction with particular focus on new insights into the role of impaired fatty acid oxidation, the transcription factor peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and sirtuins in development and progression of NAFLD. PMID:24837835

  6. Nonalcoholic fatty liver disease and metabolic syndrome in postmenopausal women.

    PubMed

    Rodrigues, Marcio H; Bruno, Anderson S; Nahas-Neto, Jorge; Santos, Maria Emilia S; Nahas, Eliana A P

    2014-05-01

    Nonalcoholic fatty liver disease (NAFLD) is considered the most common cause of chronic liver disease in the Western countries. NAFLD includes a spectrum ranging from a simple steatosis to a nonalcoholic steatohepatitis (NASH) which is defined by the presence of inflammatory infiltrate, cellular necrosis, hepatocyte ballooning, and fibrosis and cirrhosis that can eventually develop into hepatocellular carcinoma. Studies emphasize the role of insulin resistance, oxidative stress, pro-inflammatory cytokines, adipokines in the development and progression of NAFLD. It seems to be independently associated with type II diabetes mellitus, increased triglycerides, decreased HDL-cholesterol, abdominal obesity and insulin resistance. These findings are in accordance with the criteria used in the diagnosis of metabolic syndrome (MetS). Here, we will discuss the current knowledge on the epidemiology, pathophysiology and diagnosis of NAFLD and the association of metabolic syndrome in postmenopausal women.

  7. [Role of probiotics in treatment of nonalcoholic fatty liver disease].

    PubMed

    Chen, M; Wang, M C; Ni, R; Wang, J; Wang, L; Wang, G N; Zhang, L Y

    2017-01-20

    Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in China and manifests as simple fatty liver, non-alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. Studies have shown that intestinal flora can affect the development and progression of NAFLD via the "gut-liver axis" . Probiotics are active microorganisms with beneficial effects on the host, and more and more studies have found that probiotics play a positive role in improving NAFLD. They are cheaper, less harmful, and safer compared with antibiotics and surgery, and therefore, it may become a new method for the prevention and treatment of NAFLD. This article reviews the research advances in probiotics in the treatment of NAFLD, in order to provide a basis for the treatment of NAFLD using probiotics.

  8. Animal Models of Nonalcoholic Steatohepatitis: Eat, Delete, and Inflame.

    PubMed

    Ibrahim, Samar H; Hirsova, Petra; Malhi, Harmeet; Gores, Gregory J

    2016-05-01

    With the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become a public health problem with increasing prevalence. The mechanism of disease progression remains obscure and effective therapy is lacking. Therefore, there is a need to understand the pathogenic mechanisms responsible for disease development and progression in order to develop innovative therapies. To accomplish this goal, experimental animal models that recapitulate the human disease are necessary, especially, since causative mechanistic studies of NAFLD are more difficult or unethical to perform in humans. A large number of studies regarding the pathophysiology and treatment of nonalcoholic steatohepatitis (NASH) have been undertaken in mice to model human NAFLD and NASH. This review discusses the known dietary, genetic, and inflammation-based animal models of NASH described in recent years, with a focus on the major advances made in this field.

  9. Intrauterine Growth Retardation and Nonalcoholic Fatty Liver Disease in Children

    PubMed Central

    Alisi, Anna; Panera, Nadia; Agostoni, Carlo; Nobili, Valerio

    2011-01-01

    Intrauterine growth retardation (IUGR), the most important cause of perinatal mortality and morbidity, is defined as a foetal growth less than normal for the population, often used as synonym of small for gestational age (SGA). Studies demonstrated the relationships between metabolic syndrome (MS) and birthweight. This study suggested that, in children, adolescents, and adults born SGA, insulin resistance could lead to other metabolic disorders: type 2 diabetes (DM2), dyslipidemia, and nonalcoholic fatty liver disease (NAFLD). NAFLD may evolve to nonalcoholic steatohepatitis (NASH), and it is related to the development of MS. Lifestyle intervention, physical activity, and weight reduction represent the mainstay of NAFLD therapy. In particular, a catch-up growth reduction could decrease the risk to develop MS and NAFLD. In this paper, we outline clinical and experimental evidences of the association between IUGR, metabolic syndrome, insulin resistance, and NAFLD and discuss on a possible management to avoid the risk of MS in adulthood. PMID:22190925

  10. Animal Models of Nonalcoholic Steatohepatitis: Eat, Delete, and Inflame

    PubMed Central

    Ibrahim, Samar H.; Hirsova, Petra; Malhi, Harmeet; Gores, Gregory J.

    2016-01-01

    With the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become a public health problem with increasing prevalence. The mechanism of disease progression remains obscure and effective therapy is lacking. Therefore, there is a need to understand the pathogenic mechanisms responsible for disease development and progression in order to develop innovative therapies. To accomplish this goal, experimental animal models that recapitulate the human disease are necessary, especially, since causative mechanistic studies of NAFLD are more difficult or unethical to perform in humans. A large number of studies regarding the pathophysiology and treatment of NASH have been undertaken in mice to model human NAFLD and nonalcoholic steatohepatitis (NASH). This review discusses the known dietary, genetic and inflammation based animal models of NASH described in recent years, with a focus on the major advances made in this field. PMID:26626909

  11. Nonalcoholic fatty liver disease as a multi-systemic disease.

    PubMed

    Fotbolcu, Hakan; Zorlu, Elçin

    2016-04-28

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. NAFLD includes a wide spectrum of liver conditions ranging from simple steatosis to nonalcoholic steatohepatitis and advanced hepatic fibrosis. NAFLD has been recognized as a hepatic manifestation of metabolic syndrome linked with insulin resistance. NAFLD should be considered not only a liver specific disease but also an early mediator of systemic diseases. Therefore, NAFLD is usually associated with cardiovascular disease, chronic kidney disease, type 2 diabetes, obesity, and dyslipidemia. NAFLD is highly prevalent in the general population and is associated with increased cardiovascular morbidity and mortality. The underlying mechanisms and pathogenesis of NAFLD with regard to other medical disorders are not yet fully understood. This review focuses on pathogenesis of NAFLD and its relation with other systemic diseases.

  12. Non-Alcoholic Fatty Pancreatic Disease: A Review of Literature.

    PubMed

    Tariq, Hassan; Nayudu, Suresh; Akella, Sai; Glandt, Mariela; Chilimuri, Sridhar

    2016-12-01

    There is an epidemic of obesity worldwide. The prevalence of obesity has doubled over the last three decades. Obesity, especially abdominal obesity is associated with insulin resistance that can lead to pancreatic steatosis and non-alcoholic fatty pancreatic disease (NAFPD). NAFPD describes a phenotype entity ranging from deposition of fat in the pancreas to pancreatic inflammation, and resultant fibrosis, which is similar to that of non-alcoholic fatty liver disease (NAFLD). NAFPD may represent a meaningful manifestation of metabolic syndrome. Pancreatic steatosis can be diagnosed on ultrasound, computed tomography (CT) scan or magnetic resonance imaging (MRI). In addition to a correlation between pancreatic steatosis and metabolic syndrome, pancreatic steatosis may lead to a worse outcome in pancreatitis and may be an etiological factor in pancreatic cancer, but we need further research to examine the associations, pathophysiology, and the impact of pancreatic steatosis and NAFPD on the human health.

  13. Non-Alcoholic Fatty Pancreatic Disease: A Review of Literature

    PubMed Central

    Tariq, Hassan; Nayudu, Suresh; Akella, Sai; Glandt, Mariela; Chilimuri, Sridhar

    2016-01-01

    There is an epidemic of obesity worldwide. The prevalence of obesity has doubled over the last three decades. Obesity, especially abdominal obesity is associated with insulin resistance that can lead to pancreatic steatosis and non-alcoholic fatty pancreatic disease (NAFPD). NAFPD describes a phenotype entity ranging from deposition of fat in the pancreas to pancreatic inflammation, and resultant fibrosis, which is similar to that of non-alcoholic fatty liver disease (NAFLD). NAFPD may represent a meaningful manifestation of metabolic syndrome. Pancreatic steatosis can be diagnosed on ultrasound, computed tomography (CT) scan or magnetic resonance imaging (MRI). In addition to a correlation between pancreatic steatosis and metabolic syndrome, pancreatic steatosis may lead to a worse outcome in pancreatitis and may be an etiological factor in pancreatic cancer, but we need further research to examine the associations, pathophysiology, and the impact of pancreatic steatosis and NAFPD on the human health. PMID:28058076

  14. Statins in nonalcoholic fatty liver disease and steatohepatitis: updated review.

    PubMed

    Nseir, William; Mahamid, Mahmud

    2013-03-01

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that refers to the presence of hepatic steatosis without significant intake of alcohol. NAFLD is an asymptomatic disease that can progress to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The most common cause of mortality in patients with NAFLD or NASH is cardiovascular disease (CVD). Currently, the treatment of NAFLD focuses on gradual weight loss and life style modifications. However, multifactorial treatment of NAFLD or NASH risk factors may be needed to reduce the likelihood of these patients developing CVD. This review discusses the mechanisms that link hyperlipidemia and NAFLD. In addition, the review focuses on the safety and efficacy of statins in patients with NAFLD or NASH, and their effect on the extent of hepatic steatosis and fibrosis based on human studies.

  15. Nonalcoholic Fatty Liver Disease Review: Diagnosis, Treatment, and Outcomes.

    PubMed

    Ahmed, Aijaz; Wong, Robert J; Harrison, Stephen A

    2015-11-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal serum aminotransferase levels in both developed and developing countries. Patients with nonalcoholic steatohepatitis (NASH), a subset of NAFLD, are at risk for progressive liver disease and in need of effective treatment options. A practical approach may be pursued by identifying patients with NAFLD with the highest likelihood for histologic evidence of NASH. Despite decades of clinical trials, no single treatment can be recommended to all patients with NASH. Importantly, there is no evidence that pioglitazone or vitamin E improves fibrosis. Bariatric surgeries may improve hepatic histology in morbidly obese patients with NASH, although randomized clinical trials are lacking. Currently, NASH is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. The primary and secondary prevention of NAFLD may require aggressive strategies for managing obesity, diabetes, and metabolic syndrome.

  16. Non-alcoholic Wernicke's encephalopathy: broadening the clinicoradiological spectrum

    PubMed Central

    Santos Andrade, C; Tavares Lucato, L; da Graça Morais Martin, M; Joaquina Marques-Dias, M; Antonio Pezzi Portela, L; Scarabôtolo Gattás, G; da Costa Leite, C

    2010-01-01

    Wernicke's encephalopathy (WE) is a serious neurological disorder secondary to thiamine deficiency. Improved recognition by radiologists and allied health providers of the different clinical settings and imaging findings associated with this emergency can optimise the management of this condition and help prevent its severe consequences. The aim of this study is to illustrate the broad clinicoradiological spectrum of non-alcoholic WE, while emphasising atypical MRI findings. PMID:20223908

  17. Betaine and nonalcoholic steatohepatitis: back to the future?

    PubMed

    Mukherjee, Sandeep

    2011-08-28

    Nonalcoholic steatohepatitis (NASH) is an important indication for liver transplantation in many Western countries. Obesity and insulin resistance are the two most common risk factors for NASH, which can lead to recurrent NASH after liver transplantation. There is currently no approved therapy for NASH, and treatment is directed at risk factor modification and lifestyle changes. Betaine has been used for NASH, with mixed results, and may show promise in conjunction with other agents in clinical trials.

  18. Nonalcoholic fatty liver disease: molecular pathways and therapeutic strategies

    PubMed Central

    2013-01-01

    Along with rising numbers of patients with metabolic syndrome, the prevalence of nonalcoholic fatty liver disease (NAFLD) has increased in proportion with the obesity epidemic. While there are no established treatments for NAFLD, current research is targeting new molecular mechanisms that underlie NAFLD and associated metabolic disorders. This review discusses some of these emerging molecular mechanisms and their therapeutic implications for the treatment of NAFLD. The basic research that has identified potential molecular targets for pharmacotherapy will be outlined. PMID:24209497

  19. [Nonalcoholic carbonated beverage based on a potato concentrate].

    PubMed

    Lovkis, Z V; Litviak, V V; Petiushev, N N; Pochitskaia, I M

    2007-01-01

    The technology of reception of a concentrate is developed and introduced on the basis of potato, and also nonalcoholic aerated drink "Mikola" prepared on its basis. The major importance in formation organoleptic properties of a concentrate and a drink belongs to reaction melanoidin formation. The developed technologies can form a basis for creation of the whole spectrum of domestic soft drinks of the functional purpose.

  20. Cerebrovascular Alterations in Alcoholic and Non-Alcoholic Psychiatric Patients

    DTIC Science & Technology

    2005-12-19

    19-12-2005 article 12003-04; 2005 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Cerebrovascular alterations in alcoholic and non-alcoholic patients. 5b...University Responsible publisher is the Dean of the Faculty Printed in the Printing offices of the Faculty 47 CEREBROVASCULAR ALTERATIONS IN ALCOHOLIC...The US vs. Hungarian group comparison confimned the cerebrovascular alteration in Hun- garian alcoholic group. Elevated KEG values in alcoholics may

  1. Etiology and therapeutic approach to elevated lactate

    PubMed Central

    Andersen, Lars W.; Mackenhauer, Julie; Roberts, Jonathan C.; Berg, Katherine M.; Cocchi, Michael N.; Donnino, Michael W.

    2014-01-01

    Lactate levels are commonly evaluated in acutely ill patients. Although most commonly used in the context of evaluating shock, lactate can be elevated for many reasons. While tissue hypoperfusion is probably the most common cause of elevation, many other etiologies or contributing factors exist. Clinicians need to be aware of the many potential causes of lactate elevation as the clinical and prognostic importance of an elevated lactate varies widely by disease state. Moreover, specific therapy may need to be tailored to the underlying cause of elevation. The current review is based on a comprehensive PubMed search and contains an overview of the pathophysiology of lactate elevation followed by an in-depth look at the varied etiologies, including medication-related causes. The strengths and weaknesses of lactate as a diagnostic/prognostic tool and its potential use as a clinical endpoint of resuscitation will be discussed. The review ends with some general recommendations on management of patients with elevated lactate. PMID:24079682

  2. Current trends in lactate metabolism: introduction.

    PubMed

    Gladden, L Bruce

    2008-03-01

    In September 2006, at the Integrative Physiology of Exercise meeting in Indianapolis, IN, a symposium entitled "Current Trends in Lactate Metabolism" was presented. This short paper introduces two papers from that symposium. The first paper by L. Bruce Gladden briefly summarizes key pieces of evidence that support the cell-to-cell lactate shuttle, a concept that is no longer an hypothesis but that, instead, is now an established theory that provides the context for discussions of whole body metabolism. Gladden also offers a critical appraisal of the intracellular lactate shuttle and evaluates an ongoing controversy relative to the role of lactate in acid-base balance. In the second paper, Hashimoto and Brooks provide their evidence in support of the intracellular lactate shuttle and a lactate oxidation complex in the inner mitochondrial membrane. They also postulate that lactate is a cell-signaling molecule, "lactormone," that can upregulate gene and protein expression. Both papers have been updated since their original presentations and represent the current state of knowledge.

  3. Evaluation of the Lactate Plus monitor for plasma lactate concentration measurement in dogs.

    PubMed

    Nye, Carolyn J; Musulin, Sarah E; Hanel, Rita M; Mariani, Christopher L

    2017-01-01

    To compare the Lactate Plus handheld monitor to a reference blood gas analyzer for determining plasma lactate concentrations in canine whole blood. Prospective observational study. University teaching hospital. Ninety-four dogs hospitalized or admitted through the emergency service provided 125 blood samples. Only dogs that required a venous or arterial blood gas evaluation as a part of their diagnostic assessment or ongoing management were included. None. Canine whole blood samples were assayed for plasma lactate concentration with a reference blood gas analyzer and the Lactate Plus monitor. Correlation and Bland-Altman analyses were used to compare results between the 2 methods. A subset of blood samples was repeatedly analyzed with the Lactate Plus to assess monitor precision. Plasma lactate measurements from the Lactate Plus monitor showed excellent correlation with those from the reference analyzer (ρ = 0.98, P < 0.0001). Bland-Altman analysis revealed a small bias (0.1296). Agreement between the 2 methods was less consistent for lactate concentrations >5 mmol/L. The coefficient of variation ranged from 0-26.2% (median, 3.7%) and was <15% for 50/53 samples. The Lactate Plus provides a fast and affordable method to measure plasma lactate concentration in dogs. Results showed excellent agreement with the reference analyzer and precision of the instrument was acceptable. © Veterinary Emergency and Critical Care Society 2016.

  4. A comparison of the fibrotic potential of nonalcoholic fatty liver disease and chronic hepatitis C.

    PubMed

    Charlotte, Fréderic; Le Naour, Gilles; Bernhardt, Carole; Poynard, Thierry; Ratziu, Vlad

    2010-08-01

    In nonalcoholic fatty liver disease the amount of fibrosis for individual histologic stages is unknown. To better understand the fibrotic potential of nonalcoholic fatty liver disease, we compared the amount of fibrosis in nonalcoholic fatty liver disease versus chronic hepatitis C virus patients. The area of fibrosis for equivalent fibrosis stages was measured by micromorphometry in 70 nonalcoholic fatty liver disease and 70 matched, untreated, chronic hepatitis C virus controls. The area of fibrosis correlated with Brunt stage (r = 0.71; P < .001) in nonalcoholic fatty liver disease and METAVIR stage (r = 0.58; P < .001) in chronic hepatitis C virus. Mean area of fibrosis was similar in nonalcoholic fatty liver disease and chronic hepatitis C virus patients (7.77% versus 7.70%). Although chronic hepatitis C virus patients displayed higher area of fibrosis in early disease (no or mild fibrosis), nonalcoholic fatty liver disease and chronic hepatitis C virus patients had similar area of fibrosis in more advanced disease (7.83% versus 8.06%, respectively; P = .86 for bridging fibrosis; and 16.62% versus 12.98%, respectively; P = .29 for cirrhosis). The area of fibrosis was similar in Brunt stage 3 nonalcoholic fatty liver disease and METAVIR stage 2 chronic hepatitis C virus, the usual threshold for initiating therapy. The area of steatosis declined with increasing fibrosis stages confirming the early loss of liver fat with progressive fibrosis in nonalcoholic fatty liver disease. Fibrosis is as abundant in nonalcoholic fatty liver disease as in chronic hepatitis C virus, especially in the advanced stages of the disease. The fibrotic potential of nonalcoholic fatty liver disease is as severe as that of chronic hepatitis C virus.

  5. Stat5a increases lactation of dairy cow mammary gland epithelial cells cultured in vitro.

    PubMed

    Liu, Xiao Fei; Li, Meng; Li, Qing Zhang; Lu, Li Min; Tong, Hui Li; Gao, Xue Jun

    2012-10-01

    Signal transducer and activator of transcription 5a (Stat5a) transduces signals of extracellular cytokines and growth factors to the nucleus of mammary gland epithelial cells and thereby regulates gene transcription during pregnancy, lactation, and weaning. However, its function on the milk production of dairy cows needs further investigation. In this experiment, the effects of Stat5a on lactation ability of dairy cow mammary gland epithelial cells (DCMECs) were analyzed. Eukaryotic expression vector pcDNA3.1+-stat5a-αS1 was constructed by inserting stat5a gene into the plasmid vector pcDNA3.1+ and replacing CMV promoter with α-S1-casein 5' flanking sequence. The recombinant vector was stably transfected into DCMECs after geneticin (G418) selection. The proliferation and viability of DCMECs, expression of β-casein and stat5a gene, and the content of lactose were detected. The results showed that stat5a gene in eukaryotic expression vector pcDNA3.1+-stat5a-αS1 was highly expressed in DCMECs and could increase the lactation ability of DCMECs. The associativity of Stat5a with nutrients on the lactation ability of DCMECs was also evaluated. Lysine (Lys), methionine (Met), sodium acetate, β-sodium hydroxybutyrate, and glucose all had more positive effects on the lactation function of DCMECs after pcDNA3.1+-stat5a-αS1 transfection. The proliferation and viability of DCMECs, expression of β-casein and stat5a gene, and contents of lactose and triglyceride were detected. The results revealed that nutrients could promote expression of Stat5a gene to increase lactation of DCMECs. These data help to clarify the function of stat5 gene on lactation and gene regulatory networks linking stat5a.

  6. Management of Non-alcoholic Fatty Liver Disease and Steatohepatitis

    PubMed Central

    Le, Thuy-Anh; Loomba, Rohit

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver enzymes and chronic liver disease in the US with expected rise in incidence paralleling the epidemic of obesity. A subset of patients with NAFLD have the progressive form of NAFLD that is termed non-alcoholic steatohepatitis (NASH), which is characterized by specific features on liver histology including hepatocellular ballooning degeneration, lobular inflammation, and zone-3 steatosis with or without peri-sinusoidal fibrosis. Non-alcoholic steatohepatitis can progress to cirrhosis and result in liver-related death. Insulin resistance is commonly seen in patients with NASH and often co-exists with other features of the metabolic syndrome including hypertension, hyperlipidemia, and obesity. Although weight loss through lifestyle modifications including dietary changes and increased physical exercise remains the backbone of management of NASH, it has proved challenging for patients to achieve and maintain weight loss goals. Thus, it is often necessary to couple lifestyle changes with another pharmacologic treatment for NASH. Insulin sensitizers including the biguanides (metformin), thiazolidinediones (pioglitazone and rosiglitazone), and glucagon-like peptide-1 receptor agonists (exenatide) are large groups of medications that have been studied for the treatment of NASH. Other agents with anti-inflammatory, anti-apoptotic, or anti-fibrotic properties which have been studied in NASH include vitamin E, pentoxifylline, betaine, and ursodeoxycholic acid. This review will provide a detailed summary on the clinical data behind the full spectrum of treatments that exist for NASH and suggest management recommendations. PMID:25755424

  7. Pharmacologic therapy for nonalcoholic fatty liver disease in adults.

    PubMed

    Malinowski, Scott S; Byrd, Jennifer S; Bell, Allison M; Wofford, Marion R; Riche, Daniel M

    2013-02-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of triglycerides in hepatocytes in the absence of excessive alcohol intake, ranging in severity from simple steatosis to nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis can ultimately progress to cirrhosis and hepatocellular carcinoma. NAFLD is associated with cardiometabolic risk factors and is the most common chronic liver disease among adults in the Western Hemisphere. Although simple steatosis is generally considered a self-limiting disease, evidence suggests an increased risk of cardiovascular disease, and, less conclusively, mortality, among individuals with NAFLD and/or NASH. The current standard of care for the treatment of patients with NAFLD focuses on lifestyle interventions, particularly diet and exercise. There is a lack of consensus regarding the most effective and appropriate pharmacologic therapy. A PubMed search was conducted using the medical subject heading terms "fatty liver" and "steatohepatitis." This review focuses on the current pharmacologic options available for treating adults with NAFLD and/or NASH. Continued investigation of drugs or combinations that improve NAFLD progression is crucial. Clinicians, particularly pharmacists, must take an active role in identification and appropriate selection of pharmacotherapy for NAFLD. © 2013 Pharmacotherapy Publications, Inc.

  8. Transcriptional networks implicated in human nonalcoholic fatty liver disease.

    PubMed

    Ye, Hua; Liu, Wei

    2015-10-01

    The transcriptome of nonalcoholic fatty liver disease (NAFLD) was investigated in several studies. However, the implications of transcriptional networks in progressive NAFLD are not clear and mechanisms inducing transition from nonalcoholic simple fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) are still elusive. The aims of this study were to (1) construct networks for progressive NAFLD, (2) identify hub genes and functional modules in these networks and (3) infer potential linkages among hub genes, transcription factors and microRNAs (miRNA) for NAFLD progression. A systems biology approach by combining differential expression analysis and weighted gene co-expression network analysis (WGCNA) was utilized to dissect transcriptional profiles in 19 normal, 10 NAFL and 16 NASH patients. Based on this framework, 3 modules related to chromosome organization, proteasomal ubiquitin-dependent protein degradation and immune response were identified in NASH network. Furthermore, 9 modules of co-expressed genes associated with NAFL/NASH transition were found. Further characterization of these modules defined 13 highly connected hub genes in NAFLD progression network. Interestingly, 11 significantly changed miRNAs were predicted to target 10 of the 13 hub genes. Characterization of modules and hub genes that may be regulated by miRNAs could facilitate the identification of candidate genes and pathways responsible for NAFL/NASH transition and lead to a better understanding of NAFLD pathogenesis. The identified modules and hub genes may point to potential targets for therapeutic interventions.

  9. Management of non-alcoholic fatty liver disease in 2015

    PubMed Central

    Malhotra, Neel; Beaton, Melanie D

    2015-01-01

    There is no single pharmacologic therapy that has been approved to treat nonalcoholic fatty liver disease in the general population. The backbone of therapy currently includes intensive lifestyle modification with established targets for diet and weight loss. The use of unsweetened, unfiltered coffee along with limiting high fructose corn syrup have emerged as beneficial dietary recommendations. The use of empiric oral hypoglycemic agents and vitamin E, however, has not been widely accepted. Developing bariatric surgical techniques are promising, but additional studies with long-term follow up are needed before it can be widely recommended. Finally, liver transplantation is an increasingly frequent consideration once complications of end-stage disease have developed. The future treatment of those with nonalcoholic fatty liver disease will likely involve a personalized approach. The importance of the gut microbiome in mediating hepatocyte inflammation and intestinal permeability is emerging and may offer avenues for novel treatment. The study of anti-fibrotic agents such as pentoxifylline and FXR agonists hold promise and new pathways, such as hepatocyte cannabinoid receptor antagonists are being studied. With the incidence of obesity and the metabolic syndrome increasing throughout the developed world, the future will continue to focus on finding novel agents and new applications of existing therapies to help prevent and to mediate the progression of nonalcoholic fatty liver disease. PMID:26730275

  10. Management of Non-alcoholic Fatty Liver Disease and Steatohepatitis.

    PubMed

    Le, Thuy-Anh; Loomba, Rohit

    2012-06-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver enzymes and chronic liver disease in the US with expected rise in incidence paralleling the epidemic of obesity. A subset of patients with NAFLD have the progressive form of NAFLD that is termed non-alcoholic steatohepatitis (NASH), which is characterized by specific features on liver histology including hepatocellular ballooning degeneration, lobular inflammation, and zone-3 steatosis with or without peri-sinusoidal fibrosis. Non-alcoholic steatohepatitis can progress to cirrhosis and result in liver-related death. Insulin resistance is commonly seen in patients with NASH and often co-exists with other features of the metabolic syndrome including hypertension, hyperlipidemia, and obesity. Although weight loss through lifestyle modifications including dietary changes and increased physical exercise remains the backbone of management of NASH, it has proved challenging for patients to achieve and maintain weight loss goals. Thus, it is often necessary to couple lifestyle changes with another pharmacologic treatment for NASH. Insulin sensitizers including the biguanides (metformin), thiazolidinediones (pioglitazone and rosiglitazone), and glucagon-like peptide-1 receptor agonists (exenatide) are large groups of medications that have been studied for the treatment of NASH. Other agents with anti-inflammatory, anti-apoptotic, or anti-fibrotic properties which have been studied in NASH include vitamin E, pentoxifylline, betaine, and ursodeoxycholic acid. This review will provide a detailed summary on the clinical data behind the full spectrum of treatments that exist for NASH and suggest management recommendations.

  11. Lactate as a Biomarker for Sleep

    PubMed Central

    Naylor, Erik; Aillon, Daniel V.; Barrett, Brian S.; Wilson, George S.; Johnson, David A.; Johnson, Donna A.; Harmon, Hans P.; Gabbert, Seth; Petillo, Peter A.

    2012-01-01

    Study Objectives: An ideal biomarker for sleep should change rapidly with sleep onset, remain at a detectably differential level throughout the sleep period, and exhibit a rapid change with waking. Currently, no molecular marker has been identified that exhibits all three properties. This study examined three substances (lactate, glucose, and glutamate) for suitability as a sleep biomarker. Design: Using amperometric biosensor technology in conjunction with electroencephalograph (EEG) and electromyograph (EMG) monitoring, extracellular concentrations of lactate and glucose (Cohort 1) as well as lactate and glutamate (Cohort 2) were recorded over multiple sleep/wake cycles. Patients or Participants: There were 12 C57Bl/6J male mice (3-5 mo old). Interventions: Sleep and waking transitions were identified using EEG recordings. Extracellular concentrations of lactate, glucose, and glutamate were evaluated before and during transition events as well as during extended sleep and during a 6-h sleep deprivation period. Measurements and Results: Rapid and sustained increases in cortical lactate concentration (approximately 15 μM/min) were immediately observed upon waking and during rapid eye movement sleep. Elevated lactate concentration was also maintained throughout a 6-h period of continuous waking. A persistent and sustained decline in lactate concentration was measured during nonrapid eye movement sleep. Glutamate exhibited similar patterns, but with a much slower rise and decline (approximately 0.03 μM/min). Glucose concentration changes did not demonstrate a clear correlation with either sleep or wake. Conclusions: These findings indicate that extracellular lactate concentration is a reliable sleep/wake biomarker and can be used independently of the EEG signal. Citation: Naylor E; Aillon DV; Barrett BS; Wilson GS; Johnson DA; Johnson DA; Harmon HP; Gabbert S; Petillo PA. Lactate as a biomarker for sleep. SLEEP 2012;35(9):1209-1222. PMID:22942499

  12. Lactational mastitis caused by Streptococcus lactarius.

    PubMed

    Tena, Daniel; Fernández, Cristina; López-Garrido, Beatriz; Pérez-Balsalobre, Mercedes; Losa, Cristina; Medina-Pascual, María José; Sáez-Nieto, Juan Antonio

    2016-08-01

    Human infections caused by Streptococcus lactarius have not been previously reported. In the present report, we describe a lactational mastitis caused by this organism. The infection occurred in a 28-year-old breast-feeding female, with a 10-days history of moderate pain on the right breast. The patient was cured after antibiotic treatment with levofloxacin for 21 days. Our case shows that S. lactarius should be considered as a cause of lactational mastitis. The introduction of molecular microbiology techniques can be extremely useful for knowing the implication of streptococci in lactational mastitis.

  13. An In Vitro Model of the Horse Gut Microbiome Enables Identification of Lactate-Utilizing Bacteria That Differentially Respond to Starch Induction

    PubMed Central

    Biddle, Amy S.; Black, Samuel J.; Blanchard, Jeffrey L.

    2013-01-01

    Laminitis is a chronic, crippling disease triggered by the sudden influx of dietary starch. Starch reaches the hindgut resulting in enrichment of lactic acid bacteria, lactate accumulation, and acidification of the gut contents. Bacterial products enter the bloodstream and precipitate systemic inflammation. Hindgut lactate levels are normally low because specific bacterial groups convert lactate to short chain fatty acids. Why this mechanism fails when lactate levels rapidly rise, and why some hindgut communities can recover is unknown. Fecal samples from three adult horses eating identical diets provided bacterial communities for this in vitro study. Triplicate microcosms of fecal slurries were enriched with lactate and/or starch. Metabolic products (short chain fatty acids, headspace gases, and hydrogen sulfide) were measured and microbial community compositions determined using Illumina 16S rRNA sequencing over 12-hour intervals. We report that patterns of change in short chain fatty acid levels and pH in our in vitro system are similar to those seen in in vivo laminitis induction models. Community differences between microcosms with disparate abilities to clear excess lactate suggest profiles conferring resistance of starch-induction conditions. Where lactate levels recover following starch induction conditions, propionate and acetate levels rise correspondingly and taxa related to Megasphaeraelsdenii reach levels exceeding 70% relative abundance. In lactate and control cultures, taxa related to Veillonellamontpellierensis are enriched as lactate levels fall. Understanding these community differences and factors promoting the growth of specific lactate utilizing taxa may be useful to prevent acidosis under starch-induction conditions. PMID:24098591

  14. An in vitro model of the horse gut microbiome enables identification of lactate-utilizing bacteria that differentially respond to starch induction.

    PubMed

    Biddle, Amy S; Black, Samuel J; Blanchard, Jeffrey L

    2013-01-01

    Laminitis is a chronic, crippling disease triggered by the sudden influx of dietary starch. Starch reaches the hindgut resulting in enrichment of lactic acid bacteria, lactate accumulation, and acidification of the gut contents. Bacterial products enter the bloodstream and precipitate systemic inflammation. Hindgut lactate levels are normally low because specific bacterial groups convert lactate to short chain fatty acids. Why this mechanism fails when lactate levels rapidly rise, and why some hindgut communities can recover is unknown. Fecal samples from three adult horses eating identical diets provided bacterial communities for this in vitro study. Triplicate microcosms of fecal slurries were enriched with lactate and/or starch. Metabolic products (short chain fatty acids, headspace gases, and hydrogen sulfide) were measured and microbial community compositions determined using Illumina 16S rRNA sequencing over 12-hour intervals. We report that patterns of change in short chain fatty acid levels and pH in our in vitro system are similar to those seen in in vivo laminitis induction models. Community differences between microcosms with disparate abilities to clear excess lactate suggest profiles conferring resistance of starch-induction conditions. Where lactate levels recover following starch induction conditions, propionate and acetate levels rise correspondingly and taxa related to Megasphaeraelsdenii reach levels exceeding 70% relative abundance. In lactate and control cultures, taxa related to Veillonellamontpellierensis are enriched as lactate levels fall. Understanding these community differences and factors promoting the growth of specific lactate utilizing taxa may be useful to prevent acidosis under starch-induction conditions.

  15. Metabolomic analysis of human cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis diseases.

    PubMed

    Safaei, Akram; Arefi Oskouie, Afsaneh; Mohebbi, Seyed Reza; Rezaei-Tavirani, Mostafa; Mahboubi, Mohammad; Peyvandi, Maryam; Okhovatian, Farshad; Zamanian-Azodi, Mona

    2016-01-01

    Metabolome analysis is used to evaluate the characteristics and interactions of low molecular weight metabolites under a specific set of conditions. In cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatotic hepatitis (NASH) the liver does not function thoroughly due to long-term damage. Unfortunately the early detection of cirrhosis, HCC, NAFLD and NASH is a clinical problem and determining a sensitive, specific and predictive novel method based on biomarker discovery is an important task. On the other hand, metabolomics has been reported as a new and powerful technology in biomarker discovery and dynamic field that cause global comprehension of system biology. In this review, it has been collected a heterogeneous set of metabolomics published studies to discovery of biomarkers in researches to introduce diagnostic biomarkers for early detection and the choice of patient-specific therapies.

  16. Metabolomic analysis of human cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis diseases

    PubMed Central

    Safaei, Akram; Arefi Oskouie, Afsaneh; Mohebbi, Seyed Reza; Rezaei-Tavirani, Mostafa; Mahboubi, Mohammad; Peyvandi, Maryam; Okhovatian, Farshad; Zamanian-Azodi, Mona

    2016-01-01

    Metabolome analysis is used to evaluate the characteristics and interactions of low molecular weight metabolites under a specific set of conditions. In cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatotic hepatitis (NASH) the liver does not function thoroughly due to long-term damage. Unfortunately the early detection of cirrhosis, HCC, NAFLD and NASH is a clinical problem and determining a sensitive, specific and predictive novel method based on biomarker discovery is an important task. On the other hand, metabolomics has been reported as a new and powerful technology in biomarker discovery and dynamic field that cause global comprehension of system biology. In this review, it has been collected a heterogeneous set of metabolomics published studies to discovery of biomarkers in researches to introduce diagnostic biomarkers for early detection and the choice of patient-specific therapies. PMID:27458508

  17. Maternal Buprenorphine Maintenance and Lactation.

    PubMed

    Jansson, Lauren M; Spencer, Nancy; McConnell, Krystle; Velez, Martha; Tuten, Michelle; Harrow, Cheryl A; Jones, Hendrée E; Swortwood, Madeleine J; Barnes, Allan J; Scheidweiler, Karl B; Huestis, Marilyn A

    2016-11-01

    In addition to the well-known benefits of human milk and breastfeeding for the mother and infant, breastfeeding may mitigate neonatal abstinence syndrome severity in prenatally opioid-exposed infants. However, lack of conclusive data regarding the extent of the presence of buprenorphine and active metabolites in human milk makes the recommendation of breastfeeding for buprenorphine-maintained women difficult for many providers. This study seeks to determine the concentrations of buprenorphine and its active metabolites (norbuprenorphine, buprenorphine-glucuronide, and norbuprenorphine-glucuronide) in human milk, maternal plasma, and infant plasma of buprenorphine-maintained women and their infants. Up to 10 buprenorphine-maintained women provided paired breast milk and plasma samples at 2, 3, 4, 14, and 30 days postdelivery, and 9 infants provided plasma samples on day 14 of life. All samples were analyzed via liquid chromatography tandem mass spectrometry to determine concentrations of buprenorphine, norbuprenorphine, buprenorphine-glucuronide, and norbuprenorphine-glucuronide by a fully validated method. Concentrations of buprenorphine and metabolites are low in human milk and maternal plasma. Breastfed infant plasma concentrations of buprenorphine were low or undetectable and metabolite concentrations undetectable at 14 days of infant age. There were significant correlations between maternal buprenorphine dose and maternal plasma and human milk buprenorphine concentrations. These data find low concentrations of buprenorphine and metabolites in human milk and lend support to the recommendation for lactation among stable buprenorphine-maintained women. However, the correlation between maternal dose and maternal plasma and human milk buprenorphine concentrations bears further study.

  18. Comparison of the Lactate Pro and Analox GM7 blood lactate analysers.

    PubMed

    van Someren, K A; Howatson, G; Nunan, D; Thatcher, R; Shave, R

    2005-10-01

    The purpose of this study was firstly, to determine the level of agreement between the Lactate Pro and Analox GM7 for the measurement of blood lactate, and secondly, to examine whether these analysers may be used interchangeably to identify lactate parameters routinely used in the physiological assessment of athletes. Twenty well-trained male cyclists performed an incremental cycle ergometry test; duplicate blood samples were taken simultaneously throughout the test for lactate determination using the two analysers. Power output and heart rate at LT, LT1, 2 mmol.L-1, and 4 mmol.L-1 were calculated from the lactate values obtained from the two analysers. There was a strong linear relationship between the two analysers (Lactate Pro=1.4541xAnalox GM7-0.1287; R2=0.969, p<0.001; SEE=0.704) though the Lactate Pro overestimated blood lactate when compared to the Analox GM7; 95% ratio limits of agreement (Lactate Pro/Analox GM7) were 1.40x//1.35. Differences were found between analysers for power output and heart rate at LT1 (p<0.01), 2 mmol.L-1 (p<0.001), and 4 mmol.L-1 (p<0.001); no differences were found between analysers for power output or heart rate at LT. In conclusion, the average difference in blood lactate concentration measured by the Lactate Pro and the Analox GM7 was 40%, with 95% of measures differing by between 4% and 89%. This poor level of agreement and the significant differences between the two analysers in power output and heart rate associated with a number of lactate parameters indicate that these analysers should not be used interchangeably.

  19. Inducing Lactation: Breastfeeding for Adoptive Moms

    MedlinePlus

    ... Español Text Size Email Print Share Inducing Lactation: Breastfeeding for Adoptive Moms Page Content Article Body A ... a breastfeeding relationship while further stimulating milk production. Nursing Supplement While there is no way to predict ...

  20. Phyllodes Tumor in a Lactating Breast

    PubMed Central

    Murthy, Sudha S.; Raju, K. V. V. N.; Nair, Haripreetha G.

    2016-01-01

    Phyllodes tumor is attributed to a small fraction of primary tumors of the breast. Such tumors occur rarely in pregnancy and lactation. We report a case of a 25-year-old lactating mother presenting with a lump in the left breast. Core needle biopsy was opined as phyllodes tumor with lactational changes, and subsequent wide local excision confirmed the diagnosis of benign phyllodes tumor with lactational changes. The characteristic gross and microscopic findings of a well-circumscribed lesion with leaf-like fibroepithelial growth pattern and typical nonuniform or diffuse stromal proliferation with periductal accentuation even in the absence of mitotic figures can help clinch the diagnosis. Benign phyllodes is known for its recurrence and requires wide excision and close follow-up. It is vital to identify these lesions even on limited biopsies as therapeutic options differ. This case is presented for its rarity and the diagnostic challenge it poses in limited biopsy. PMID:27081326

  1. [Natural remedies during pregnancy and lactation].

    PubMed

    Gut, E; Melzer, J; von Mandach, U; Saller, R

    2004-10-01

    Up to date there is a lack of systematically gathered data on the use of natural remedies (phytotherapeutic, homeopathic, anthroposophic, spagyric, Bach and Schussler remedies) during pregnancy and lactation. The aim of this non-representative pilot study on 139 women, who came for delivery to three institutions between mid-1997 and the beginning of 1998, was to receive data about how often and within which spectrum natural remedies are used during pregnancy and lactation. During pregnancy 96% and within the lactation period 84% of the women consumed at least 1 natural remedy. Phytotherapeutic drugs were used most frequently. In contrast to the widespread use of natural remedies by pregnant women and nursing mothers in this study, little information on the effectiveness and possible risks is available. Therefore it seems necessary to examine and evaluate natural remedies used during pregnancy and lactation.

  2. Regulation of bone mineral loss during lactation

    NASA Technical Reports Server (NTRS)

    Brommage, R.; Deluca, H. F.

    1985-01-01

    The effects of varyng dietary calcium and phosphorous levels, vitamin D deficiency, oophorectomy, adrenalectomy, and simultaneous pregnancy on bone mineral loss during lactation in rats are studied. The experimental procedures and evaluations are described. The femur ash weight of lactating and nonlactating rats are calculated. The data reveals that a decrease in dietary calcium of 0.02 percent results in an increased loss of bone mineral, an increase in calcium to 1.4 percent does not lessen bone mineral loss, and bone mineral loss in vitamin D deficient rats is independent of calcium levels. It is observed that changes in dietary phosphorous level, oophorectomy, adrenalectomy, and simultaneous pragnancy do not reduce bone mineral loss during lactation. The analysis of various hormones to determine the mechanism that triggers bone mineral loss during lactation is presented.

  3. Regulation of bone mineral loss during lactation

    NASA Technical Reports Server (NTRS)

    Brommage, R.; Deluca, H. F.

    1985-01-01

    The effects of varyng dietary calcium and phosphorous levels, vitamin D deficiency, oophorectomy, adrenalectomy, and simultaneous pregnancy on bone mineral loss during lactation in rats are studied. The experimental procedures and evaluations are described. The femur ash weight of lactating and nonlactating rats are calculated. The data reveals that a decrease in dietary calcium of 0.02 percent results in an increased loss of bone mineral, an increase in calcium to 1.4 percent does not lessen bone mineral loss, and bone mineral loss in vitamin D deficient rats is independent of calcium levels. It is observed that changes in dietary phosphorous level, oophorectomy, adrenalectomy, and simultaneous pragnancy do not reduce bone mineral loss during lactation. The analysis of various hormones to determine the mechanism that triggers bone mineral loss during lactation is presented.

  4. Genetics Home Reference: lactate dehydrogenase deficiency

    MedlinePlus

    ... dehydrogenase-B pieces (subunits) of the lactate dehydrogenase enzyme. This enzyme is found throughout the body and is important ... cells. There are five different forms of this enzyme, each made up of four protein subunits. Various ...

  5. Effect of abomasal ferrous lactate infusion on phosphorus absorption in lactating dairy cows.

    PubMed

    Feng, X; Knowlton, K F; Dietrich, A D; Duncan, S

    2013-07-01

    The objective of this study was to evaluate the effect of ferrous lactate infusion on postruminal P absorption in lactating dairy cows. Four ruminally cannulated lactating cows were used in a 4×4 Latin square design with 14 d per period. Cows were fed a basal diet containing 0.39% P, providing 100% of the calculated P requirement. On d 8 to 14 of each period, each cow was infused with 0, 200, 500, or 1,250mg of Fe/d in the form of ferrous lactate solution (ferrous lactate in 1L of double-distilled water) into the abomasum. Infusate was formulated to approximate 0, 2, 5, or 12.5mg of Fe/L in drinking water with 100L of water intake/d. Total fecal collection was conducted in the last 4 d of each period to measure nutrient digestion and excretion. Dry matter intake, milk yield, and milk composition were not affected by treatment. Digestibility of DM, NDF, and nitrogen decreased linearly with increasing ferrous lactate infusion. Infusion of ferrous lactate did not affect intake and digestibility of total P, inorganic P, or phytate P. In lactating cows, P absorption was not negatively influenced by abomasally infused ferrous lactate up to 1,250mg of Fe/d. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  6. Lactate shuttling and lactate use as fuel after traumatic brain injury: metabolic considerations

    PubMed Central

    Dienel, Gerald A

    2014-01-01

    Lactate is proposed to be generated by astrocytes during glutamatergic neurotransmission and shuttled to neurons as ‘preferred' oxidative fuel. However, a large body of evidence demonstrates that metabolic changes during activation of living brain disprove essential components of the astrocyte–neuron lactate shuttle model. For example, some glutamate is oxidized to generate ATP after its uptake into astrocytes and neuronal glucose phosphorylation rises during activation and provides pyruvate for oxidation. Extension of the notion that lactate is a preferential fuel into the traumatic brain injury (TBI) field has important clinical implications, and the concept must, therefore, be carefully evaluated before implementation into patient care. Microdialysis studies in TBI patients demonstrate that lactate and pyruvate levels and lactate/pyruvate ratios, along with other data, have important diagnostic value to distinguish between ischemia and mitochondrial dysfunction. Results show that lactate release from human brain to blood predominates over its uptake after TBI, and strong evidence for lactate metabolism is lacking; mitochondrial dysfunction may inhibit lactate oxidation. Claims that exogenous lactate infusion is energetically beneficial for TBI patients are not based on metabolic assays and data are incorrectly interpreted. PMID:25204393

  7. Lactate oxidation at the mitochondria: a lactate-malate-aspartate shuttle at work

    PubMed Central

    Kane, Daniel A.

    2014-01-01

    Lactate, the conjugate base of lactic acid occurring in aqueous biological fluids, has been derided as a “dead-end” waste product of anaerobic metabolism. Catalyzed by the near-equilibrium enzyme lactate dehydrogenase (LDH), the reduction of pyruvate to lactate is thought to serve to regenerate the NAD+ necessary for continued glycolytic flux. Reaction kinetics for LDH imply that lactate oxidation is rarely favored in the tissues of its own production. However, a substantial body of research directly contradicts any notion that LDH invariably operates unidirectionally in vivo. In the current Perspective, a model is forwarded in which the continuous formation and oxidation of lactate serves as a mitochondrial electron shuttle, whereby lactate generated in the cytosol of the cell is oxidized at the mitochondria of the same cell. From this perspective, an intracellular lactate shuttle operates much like the malate-aspartate shuttle (MAS); it is also proposed that the two shuttles are necessarily interconnected in a lactate-MAS. Among the requisite features of such a model, significant compartmentalization of LDH, much like the creatine kinase of the phosphocreatine shuttle, would facilitate net cellular lactate oxidation in a variety of cell types. PMID:25505376

  8. Iodine nutrition in pregnancy and lactation.

    PubMed

    Leung, Angela M; Pearce, Elizabeth N; Braverman, Lewis E

    2011-12-01

    Adequate iodine intake is required for the synthesis of thyroid hormones that are important for normal fetal and infant neurodevelopment. In this review, we discuss iodine physiology during pregnancy and lactation, methods to assess iodine sufficiency, the importance of adequate iodine nutrition, studies of iodine supplementation during pregnancy and lactation, the consequences of hypothyroidism during pregnancy, the current status of iodine nutrition in the United States, the global efforts toward achieving universal iodine sufficiency, and substances that may interfere with iodine use.

  9. Interaction of Factors Related to Lactation Duration

    PubMed Central

    Boettcher, Joan P; Chezem, Jo Carol; Roepke, Judith; Whitaker, Tracy Adams

    1999-01-01

    Perceived social support and interpersonal dependency were studied as potential factors associated with lactation duration based upon previous breastfeeding experience. Inexperienced breastfeeding mothers perceived more social support than experienced breastfeeding mothers did. Perceived social support was not significantly correlated with lactation duration. An ancillary finding was that women providing a combination of breast milk and human milk substitutes had significantly lower social self-confidence than did mothers providing breast milk exclusively. PMID:22945984

  10. Genome-based nutrition: an intervention strategy for the prevention and treatment of obesity and nonalcoholic steatohepatitis.

    PubMed

    Roman, Sonia; Ojeda-Granados, Claudia; Ramos-Lopez, Omar; Panduro, Arturo

    2015-03-28

    Obesity and nonalcoholic steatohepatitis are increasing in westernized countries, regardless of their geographic location. In Latin America, most countries, including Mexico, have a heterogeneous admixture genome with Amerindian, European and African ancestries. However, certain high allelic frequencies of several nutrient-related polymorphisms may have been achieved by past gene-nutrient interactions. Such interactions may have promoted the positive selection of variants adapted to regional food sources. At present, the unbalanced diet composition of the Mexicans has led the country to a 70% prevalence rate of overweightness and obesity due to substantial changes in food habits, among other factors. International guidelines and intervention strategies may not be adequate for all populations worldwide because they do not consider disparities in genetic and environmental factors, and thus there is a need for differential prevention and management strategies. Here, we provide the rationale for an intervention strategy for the prevention and management of obesity-related diseases such as non-alcoholic steatohepatitis based on a regionalized genome-based diet. The components required to design such a diet should focus on the specific ancestry of each population around the world and the convenience of consuming traditional ethnic food.

  11. Loss of Hepatic CEACAM1: A Unifying Mechanism Linking Insulin Resistance to Obesity and Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Heinrich, Garrett; Ghadieh, Hilda E.; Ghanem, Simona S.; Muturi, Harrison T.; Rezaei, Khadijeh; Al-Share, Qusai Y.; Bowman, Thomas A.; Zhang, Deqiang; Garofalo, Robert S.; Yin, Lei; Najjar, Sonia M.

    2017-01-01

    The pathogenesis of human non-alcoholic fatty liver disease (NAFLD) remains unclear, in particular in the context of its relationship to insulin resistance and visceral obesity. Work on the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in mice has resolved some of the related questions. CEACAM1 promotes insulin clearance by enhancing the rate of uptake of the insulin-receptor complex. It also mediates a negative acute effect of insulin on fatty acid synthase activity. This positions CEACAM1 to coordinate the regulation of insulin and lipid metabolism. Fed a regular chow diet, global null mutation of Ceacam1 manifest hyperinsulinemia, insulin resistance, obesity, and steatohepatitis. They also develop spontaneous chicken-wire fibrosis, characteristic of non-alcoholic steatohepatitis. Reduction of hepatic CEACAM1 expression plays a significant role in the pathogenesis of diet-induced metabolic abnormalities, as bolstered by the protective effect of hepatic CEACAM1 gain-of-function against the metabolic response to dietary fat. Together, this emphasizes that loss of hepatic CEACAM1 links NAFLD to insulin resistance and obesity. PMID:28184213

  12. The Dual Role of Nrf2 in Nonalcoholic Fatty Liver Disease: Regulation of Antioxidant Defenses and Hepatic Lipid Metabolism.

    PubMed

    Chambel, Sílvia S; Santos-Gonçalves, Andreia; Duarte, Tiago L

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease with ever-growing incidence in the industrialized world. It starts with the simple accumulation of lipids in the hepatocyte and can progress to the more severe nonalcoholic steatohepatitis (NASH), which is associated with inflammation, fibrosis, and cirrhosis. There is increasing awareness that reactive oxygen species and electrophiles are implicated in the pathogenesis of NASH. Transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a positive regulator of the expression of a battery of genes involved in the protection against oxidative/electrophilic stress. In rodents, Nrf2 is also known to participate in hepatic fatty acid metabolism, as a negative regulator of genes that promote hepatosteatosis. We review relevant evidence in the literature that these two mechanisms may contribute to the protective role of Nrf2 in the development of hepatic steatosis and in the progression to steatohepatitis, particularly in young animals. We propose that age may be a key to explain contradictory findings in the literature. In summary, Nrf2 mediates the crosstalk between lipid metabolism and antioxidant defense mechanisms in experimental models of NAFLD, and the nutritional or pharmacological induction of Nrf2 represents a promising potential new strategy for its prevention and treatment.

  13. Genome-based nutrition: An intervention strategy for the prevention and treatment of obesity and nonalcoholic steatohepatitis

    PubMed Central

    Roman, Sonia; Ojeda-Granados, Claudia; Ramos-Lopez, Omar; Panduro, Arturo

    2015-01-01

    Obesity and nonalcoholic steatohepatitis are increasing in westernized countries, regardless of their geographic location. In Latin America, most countries, including Mexico, have a heterogeneous admixture genome with Amerindian, European and African ancestries. However, certain high allelic frequencies of several nutrient-related polymorphisms may have been achieved by past gene-nutrient interactions. Such interactions may have promoted the positive selection of variants adapted to regional food sources. At present, the unbalanced diet composition of the Mexicans has led the country to a 70% prevalence rate of overweightness and obesity due to substantial changes in food habits, among other factors. International guidelines and intervention strategies may not be adequate for all populations worldwide because they do not consider disparities in genetic and environmental factors, and thus there is a need for differential prevention and management strategies. Here, we provide the rationale for an intervention strategy for the prevention and management of obesity-related diseases such as non-alcoholic steatohepatitis based on a regionalized genome-based diet. The components required to design such a diet should focus on the specific ancestry of each population around the world and the convenience of consuming traditional ethnic food. PMID:25834309

  14. Loss of Hepatic CEACAM1: A Unifying Mechanism Linking Insulin Resistance to Obesity and Non-Alcoholic Fatty Liver Disease.

    PubMed

    Heinrich, Garrett; Ghadieh, Hilda E; Ghanem, Simona S; Muturi, Harrison T; Rezaei, Khadijeh; Al-Share, Qusai Y; Bowman, Thomas A; Zhang, Deqiang; Garofalo, Robert S; Yin, Lei; Najjar, Sonia M

    2017-01-01

    The pathogenesis of human non-alcoholic fatty liver disease (NAFLD) remains unclear, in particular in the context of its relationship to insulin resistance and visceral obesity. Work on the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in mice has resolved some of the related questions. CEACAM1 promotes insulin clearance by enhancing the rate of uptake of the insulin-receptor complex. It also mediates a negative acute effect of insulin on fatty acid synthase activity. This positions CEACAM1 to coordinate the regulation of insulin and lipid metabolism. Fed a regular chow diet, global null mutation of Ceacam1 manifest hyperinsulinemia, insulin resistance, obesity, and steatohepatitis. They also develop spontaneous chicken-wire fibrosis, characteristic of non-alcoholic steatohepatitis. Reduction of hepatic CEACAM1 expression plays a significant role in the pathogenesis of diet-induced metabolic abnormalities, as bolstered by the protective effect of hepatic CEACAM1 gain-of-function against the metabolic response to dietary fat. Together, this emphasizes that loss of hepatic CEACAM1 links NAFLD to insulin resistance and obesity.

  15. The Dual Role of Nrf2 in Nonalcoholic Fatty Liver Disease: Regulation of Antioxidant Defenses and Hepatic Lipid Metabolism

    PubMed Central

    Chambel, Sílvia S.; Santos-Gonçalves, Andreia; Duarte, Tiago L.

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease with ever-growing incidence in the industrialized world. It starts with the simple accumulation of lipids in the hepatocyte and can progress to the more severe nonalcoholic steatohepatitis (NASH), which is associated with inflammation, fibrosis, and cirrhosis. There is increasing awareness that reactive oxygen species and electrophiles are implicated in the pathogenesis of NASH. Transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a positive regulator of the expression of a battery of genes involved in the protection against oxidative/electrophilic stress. In rodents, Nrf2 is also known to participate in hepatic fatty acid metabolism, as a negative regulator of genes that promote hepatosteatosis. We review relevant evidence in the literature that these two mechanisms may contribute to the protective role of Nrf2 in the development of hepatic steatosis and in the progression to steatohepatitis, particularly in young animals. We propose that age may be a key to explain contradictory findings in the literature. In summary, Nrf2 mediates the crosstalk between lipid metabolism and antioxidant defense mechanisms in experimental models of NAFLD, and the nutritional or pharmacological induction of Nrf2 represents a promising potential new strategy for its prevention and treatment. PMID:26120584

  16. Are oxidative stress mechanisms the common denominator in the progression from hepatic steatosis towards non-alcoholic steatohepatitis (NASH)?

    PubMed

    Tariq, Zoon; Green, Charlotte J; Hodson, Leanne

    2014-08-01

    Non-alcoholic fatty liver disease (NAFLD) is not a single disease entity, rather it describes a spectrum of liver conditions that range from fatty liver (steatosis) to more severe steatosis coupled with marked inflammation and fibrosis [non-alcoholic steatohepatitis (NASH)] to severe liver disease such as cirrhosis and possibly hepatocellular carcinoma. Obesity, notably abdominal obesity, is a common risk factor for NAFLD. The pathogenesis from steatosis to NASH is poorly understood, and the 'two hit' model, as suggested nearly two decades ago, provides a feasible starting point for characterization of underlying mechanisms. This review will examine the oxidative stress factors ('triggers') which have been implicated as a 'second hit' in the development of primary NASH. It would be reasonable to assume that multiple, rather than single, pro-oxidative intracellular and extracellular triggers act in conjunction promoting oxidative stress that drives the development of NASH. It is likely that the common denominator of these pro-oxidative triggers is mitochondrial dysfunction. Understanding the contribution of each of these 'triggers' is an essential step in starting to understand and elucidate the mechanisms responsible for progression from steatosis to NASH, thus enabling the development of therapeutic targeting to prevent NASH development and progression.

  17. Working memory and blood lactate levels.

    PubMed

    Perciavalle, Valentina; Maci, Tiziana; Perciavalle, Vincenzo; Massimino, Simona; Coco, Marinella

    2015-11-01

    The accumulation of lactate in the blood after a high-intensity exercise is associated with an increase of lactate extractions by the brain. Previously, a negative influence of blood lactate on attentional processes has been observed. The present study was carried out to examine the association of high blood lactate levels, induced with a maximal cycling, with another cognitive domain: working memory. For evaluation of working memory two different protocols were used: the first (Self-Ordered Pointing Task) capable of analyzing non-spatial working memory requiring the ability to generate and monitor a sequence of responses and the second for evaluating motor working memory necessary to perform a motor task. The study was carried out in 30 students (15 males and 15 females) who performed exhaustive exercise. In each subject, blood lactate was measured and motor as well as non-motor forms of working memory were evaluated before the exercise, at its end as well as 15 min after the exhaustion. It was observed that an increase of blood lactate levels is associated with a worsening of both types of working memory.

  18. Composition of sow milk during lactation.

    PubMed

    Klobasa, F; Werhahn, E; Butler, J E

    1987-05-01

    The composition of sow colostrum and milk was quantitated in 25 sows at 14 time points throughout lactation. All animals belonged to the same experimental herd of German Landrace, farrowed within 4 d, and were of various lactation numbers and various litter sizes. In the first 6 h of lactation colostrum total solids (TS) and protein contents were higher, while fat and lactose contents were lower than in mature milk. Decreased total protein and whey protein contents and concomitantly increased fat and lactose content, with nearly unchanged TS levels, indicate transition from colostrum to mature milk. The high protein content of colostrum was largely due to immunoglobulin (Ig). During the first 6 h, IgG accounts for nearly all the protein in colostrum but plays a decreasing role in sow milk as lactation proceeds. After 2 wk, IgA levels begin to increase and at the end of lactation, IgA constitutes 40% of the total whey protein. No influences of lactation number and litter size on milk composition could be ascertained in this study.

  19. Sodium D-lactate infusion of panic disorder patients.

    PubMed

    Gorman, J M; Goetz, R R; Dillon, D; Liebowitz, M R; Fyer, A J; Davies, S; Klein, D F

    1990-06-01

    Nineteen patients with panic disorder received sodium D,L-lactate (racemic) and pure sodium D-lactate infusions in a pilot study. Sodium D-lactate, which is less metabolically active than L-lactate, produced panic attacks in half the patients. D-Lactate also produced hypocapnia and alkalosis, indicating hyperventilation. These findings suggest that metabolism of lactate is not necessary for the induction of panic in susceptible patients. D-Lactate appears similar to other agents that cause panic in its capacity to stimulate respiration in the preliminary study.

  20. Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease.

    PubMed

    Kawano, Yuki; Cohen, David E

    2013-04-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation in the absence of excess alcohol intake. NAFLD is the most common chronic liver disease, and ongoing research efforts are focused on understanding the underlying pathobiology of hepatic steatosis with the anticipation that these efforts will identify novel therapeutic targets. Under physiological conditions, the low steady-state triglyceride concentrations in the liver are attributable to a precise balance between acquisition by uptake of non-esterified fatty acids from the plasma and by de novo lipogenesis, versus triglyceride disposal by fatty acid oxidation and by the secretion of triglyceride-rich lipoproteins. In NAFLD patients, insulin resistance leads to hepatic steatosis by multiple mechanisms. Greater uptake rates of plasma non-esterified fatty acids are attributable to increased release from an expanded mass of adipose tissue as a consequence of diminished insulin responsiveness. Hyperinsulinemia promotes the transcriptional upregulation of genes that promote de novo lipogenesis in the liver. Increased hepatic lipid accumulation is not offset by fatty acid oxidation or by increased secretion rates of triglyceride-rich lipoproteins. This review discusses the molecular mechanisms by which hepatic triglyceride homeostasis is achieved under normal conditions, as well as the metabolic alterations that occur in the setting of insulin resistance and contribute to the pathogenesis of NAFLD.

  1. Non-alcoholic fatty liver and metabolic syndrome in children: a vicious circle.

    PubMed

    Alterio, Arianna; Alisi, Anna; Liccardo, Daniela; Nobili, Valerio

    2014-01-01

    During the last decade, paediatricians have observed a dramatic increase of non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) in children. Furthermore, several lines of evidence have reported that a large part of children with NAFLD presents one or more traits of MS making plausible that, in the coming years, these subjects may present a rapid course of disease towards more severe cirrhosis and cardiovascular disease. Genetic susceptibility and the pressure of intrauterine environment and lifestyle are all crucial to activate molecular machinery that leads to development of NAFLD and MS in childhood. In this scenario, central obesity and consequent adipose tissue inflammation are critical to promote both MS-associated metabolic dysfunctions and NAFLD-related hepatic damage. An excessive dietary intake may in fact cause a specific lipid partitioning and induce metabolic stressors, which in turn promote insulin resistance and the release of several circulating factors. These molecules, on the one hand, trigger steatosis and the inflammatory response that characterize liver damage in NAFLD, and on the other hand contribute to the onset of other features of MS. This review provides an overview of current genetic, pathogenetic and clinical evidence of the vicious circle created by NAFLD and MS in children. 2014 S. Karger AG, Basel

  2. Low-carbohydrate ketogenic diets, glucose homeostasis, and nonalcoholic fatty liver disease.

    PubMed

    Schugar, Rebecca C; Crawford, Peter A

    2012-07-01

    Obesity-associated nonalcoholic fatty liver disease (NAFLD) is highly prevalent, for which weight loss is the generally recommended clinical management. Low-carbohydrate ketogenic diets have been successful in promoting weight loss, but variations in the range of metabolic responses to these diets indicate that the effects of altering macronutrient content are not completely understood. This review focuses on the most recent findings that reveal the relationship between low-carbohydrate diets and NAFLD in rodent models and humans. Low-carbohydrate diets have been shown to promote weight loss, decrease intrahepatic triglyceride content, and improve metabolic parameters of patients with obesity. These ketogenic diets also provoke weight loss in rodents. However, long-term maintenance on a ketogenic diet stimulates the development of NAFLD and systemic glucose intolerance in mice. The relationship between ketogenic diets and systemic insulin resistance in both humans and rodents remains to be elucidated. Because low-carbohydrate ketogenic diets are increasingly employed for treatment of obesity, NAFLD, and neurological diseases such as epilepsy, understanding the long-term systemic effects of low-carbohydrate diets is crucial to the development of efficacious and safe dietary interventions.

  3. Development of an in vitro human liver system for interrogating nonalcoholic steatohepatitis

    PubMed Central

    Feaver, Ryan E.; Cole, Banumathi K.; Lawson, Mark J.; Hoang, Stephen A.; Blackman, Brett R.; Figler, Robert A.; Sanyal, Arun J.; Wamhoff, Brian R.

    2016-01-01

    A barrier to drug development for nonalcoholic steatohepatitis (NASH) is the absence of translational preclinical human-relevant systems. An in vitro liver model was engineered to incorporate hepatic sinusoidal flow, transport, and lipotoxic stress risk factors (glucose, insulin, free fatty acids) with cocultured primary human hepatocytes, hepatic stellate cells (HSCs), and macrophages. Transcriptomic, lipidomic, and functional endpoints were evaluated and compared with clinical data from NASH patient biopsies. The lipotoxic milieu promoted hepatocyte lipid accumulation (4-fold increase, P < 0.01) and a lipidomics signature similar to NASH biopsies. Hepatocyte glucose output increased with decreased insulin sensitivity. These changes were accompanied by increased inflammatory analyte secretion (e.g., IL-6, IL-8, alanine aminotransferase). Fibrogenic activation markers increased with lipotoxic conditions, including secreted TGF-β (>5-fold increase, P < 0.05), extracellular matrix gene expression, and HSC activation. Significant pathway correlation existed between this in vitro model and human biopsies. Consistent with clinical trial data, 0.5 μM obeticholic acid in this model promoted a healthy lipidomic signature, reduced inflammatory and fibrotic secreted factors, but also increased ApoB secretion, suggesting a potential adverse effect on lipoprotein metabolism. Lipotoxic stress activates similar biological signatures observed in NASH patients in this system, which may be relevant for interrogating novel therapeutic approaches to treat NASH. PMID:27942596

  4. OSAS-related inflammatory mechanisms of liver injury in nonalcoholic fatty liver disease.

    PubMed

    Paschetta, Elena; Belci, Paola; Alisi, Anna; Liccardo, Daniela; Cutrera, Renato; Musso, Giovanni; Nobili, Valerio

    2015-01-01

    Obstructive sleep apnoea syndrome (OSAS) is a common sleep disorder, affecting over 4% of the general population, and is associated with metabolic syndrome and cardiovascular disease, independent of obesity and traditional risk factors. OSAS has been recently connected to nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in the world, which can be found in 30% of the general adult population. Several studies suggest that the chronic intermittent hypoxia (CIH) of OSAS patients may per se trigger liver injury, inflammation, and fibrogenesis, promoting NAFLD development and the progression from steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In NAFLD patients, liver disease may be caused by hypoxia both indirectly by promoting inflammation and insulin resistance and directly by enhancing proinflammatory cytokine production and metabolic dysregulation in liver cells. In this review, we focus on molecular mechanisms linking OSAS to NAFLD, including hypoxia inducible factor (HIF), nuclear factor kappa B (NF-κB), YKL-40, unfolded protein response, and hypoxic adipose tissue inflammation, which all could provide novel potential therapeutic approaches for the management of NAFLD patients with OSAS.

  5. Health benefits of blue-green algae: prevention of cardiovascular disease and nonalcoholic fatty liver disease.

    PubMed

    Ku, Chai Siah; Yang, Yue; Park, Youngki; Lee, Jiyoung

    2013-02-01

    Blue-green algae (BGA) are among the most primitive life forms on earth and have been consumed as food or medicine by humans for centuries. BGA contain various bioactive components, such as phycocyanin, carotenoids, γ-linolenic acid, fibers, and plant sterols, which can promote optimal health in humans. Studies have demonstrated that several BGA species or their active components have plasma total cholesterol and triglyceride-lowering properties due to their modulation of intestinal cholesterol absorption and hepatic lipogenic gene expression. BGA can also reduce inflammation by inhibiting the nuclear factor κ B activity, consequently reducing the production of proinflammatory cytokines. Furthermore, BGA inhibit lipid peroxidation and have free radical scavenging activity, which can be beneficial for the protection against oxidative stress. The aforementioned effects of BGA can contribute to the prevention of metabolic and inflammatory diseases. This review provides an overview of the current knowledge of the health-promoting functions of BGA against cardiovascular disease and nonalcoholic fatty liver disease, which are major health threats in the developed countries.

  6. Health Benefits of Blue-Green Algae: Prevention of Cardiovascular Disease and Nonalcoholic Fatty Liver Disease

    PubMed Central

    Ku, Chai Siah; Yang, Yue; Park, Youngki

    2013-01-01

    Abstract Blue-green algae (BGA) are among the most primitive life forms on earth and have been consumed as food or medicine by humans for centuries. BGA contain various bioactive components, such as phycocyanin, carotenoids, γ-linolenic acid, fibers, and plant sterols, which can promote optimal health in humans. Studies have demonstrated that several BGA species or their active components have plasma total cholesterol and triglyceride-lowering properties due to their modulation of intestinal cholesterol absorption and hepatic lipogenic gene expression. BGA can also reduce inflammation by inhibiting the nuclear factor κ B activity, consequently reducing the production of proinflammatory cytokines. Furthermore, BGA inhibit lipid peroxidation and have free radical scavenging activity, which can be beneficial for the protection against oxidative stress. The aforementioned effects of BGA can contribute to the prevention of metabolic and inflammatory diseases. This review provides an overview of the current knowledge of the health-promoting functions of BGA against cardiovascular disease and nonalcoholic fatty liver disease, which are major health threats in the developed countries. PMID:23402636

  7. [Prevalence of and risk factors for delayed onset of lactation in Chinese lactating women in 2013].

    PubMed

    Jiang, S; Duan, Y F; Pang, X H; Bi, Y; Wang, J; Zhao, L Y; Yin, S A; Yang, Z Y

    2016-12-06

    Objective: To study the prevalence of delayed onset of lactation (later than 3 days) in lactating women in China and to analyze its influencing factors. Methods: Data were extracted from Chinese National Nutrition and Health Surveillance-Mothers, from mothers with children under 2 years of age (in 2013). A total of 11 178 women who were lactating or had lactated were selected from 55 counties of 30 provinces (excluding the Tibet Autonomous Region) in China, using the multi-stage stratified cluster randomization sampling method. Basic information, including onset of lactation, initiation of breastfeeding, breastfeeding difficulties and breastfeeding knowledge were collected using a questionnaire investigation. The prevalence of delayed onset of lactation were analyzed by the weighted processing of complex sampling from the 6(th) national population census data. A multiple logistic regression was used to analyze the factors associated with delaged onset of lactation. Results: Among 11 178 lactating women, 3 388 had an onset of lactation later than 3 d. The prevalence of delayed onset of lactation was 30.3%. After complex weighting, the prevalence of delayed onset of lactation was 31.2% (95% CI: 25.7%-36.8%) for lactating women in China. Delivery by Caesarean section (OR=1.28, 95%CI: 1.06-1.53) and initiating breastfeeding ≥4 h (OR= 2.34, 95%CI: 1.76-3.11) were the negative factors for delayed onset of lactation. Compared with those living in large cities, lactating women living in medium or small cities (OR=1.39, 95%CI: 1.05-1.84) had a higher risk of delayed onset of lactation. Compared with the lactating women doing housework, the risk of delayed onset of lactation was lower (P<0.05) among those whose occupations were as leaders of Enterprises/Institutions (OR=0.68, 95%CI: 0.47-0.99), in catering and service trades (OR=0.61, 95%CI: 0.43-0.86), in agriculture/forestry/fishery/herdsmen fields (OR=0.65, 95%CI: 0.44-0.96) and who were unemployed (OR= 0.64, 95%CI: 0

  8. Nursing practices and lactation amenorrhoea.

    PubMed

    Elias, M F; Teas, J; Johnston, J; Bora, C

    1986-01-01

    The purpose of this study is to test the hypothesis that nursing behavior is an independent underlying factor of importance in duration of amenorrhea. Multivariate analysis is applied to information on frequency and duration of nursing practices, maternal age, and nutritional status assessed by weight for height in a sample of 32 middle-class American women with a wide range of nursing behavior. The mothers were followed for 2 years postpartum, data being collected during 8 home visits by interview and by nursing records kept by the mothers. Amenorrhea lasted 1.3 to 27.1 months in the sample as a whole. Those women who nursed frequently (8/day) during exclusive breastfeeding remained amenorrheic longer than infrequent nursers, introduced supplements later, and did not resume menses as promptly thereafter. They continued an hour or more of night nursing during supplemented nursing. Duration of exclusive nursing and night nursing after supplementation were the major influences on duration of amenorrhea. This strong association favors the hypothesis that the underlying factor is nursing behavior. Mother's age, weight-for-height, and nursing frequency before supplementation showed no significant effect. Those women who introduced supplements late and maintained at least an hour of night nursing had a prolonged period of amenorrhea. The median for this group was 6-10 months longer than that for those who started supplements early and/or reduced subsequent night nursing to less than an hour. The recommendation that women must suckle their babies at least 5 times a day with a total suckling duration of more than 65 minutes per day is not sufficient. The findings reported here suggest that if women nurse exclusively for the 1st half year, maintaining night nursing after introducing supplements is important. If they supplement earlier, then they will lose the contraceptive protection of lactation, irrespective of how they nurse.

  9. Continuous lactation effects on mammary remodeling during late gestation and lactation in dairy goats.

    PubMed

    Safayi, S; Theil, P K; Hou, L; Engbaek, M; Nørgaard, J V; Sejrsen, K; Nielsen, M O

    2010-01-01

    The present study aimed to 1) elucidate whether continuous milking during late gestation in dairy goats negatively affects mammary remodeling and hence milk production in the subsequent lactation, and 2) identify the regulatory factors responsible for changes in cell turnover and angiogenesis in the continuously lactating mammary gland. Nine multiparous dairy goats were used. One udder half was dried off approximately 9 wk prepartum (normal lactation; NL), and the other udder half of the same goat was milked continuously (continuous lactation; CL) until parturition or until the half-udder milk yields had dropped to below 50 g/d. Mammary biopsies were obtained from each udder half just before the NL gland was dried off (before dry period), within the first 2 wk after drying-off (early dry period, samples available only for NL glands), in the mid dry period, within the last 2 wk before parturition (late dry period), and at d 1 (the day of parturition), 3, 10, 60, and 180 of lactation. Mammary morphology was characterized in biopsies by quantitative histology, and cell turnover was determined by immunohistochemistry (terminal deoxynucleotidyl transferase dUTP nick end labeling and Ki-67). Transcription of genes encoding factors involved in mammary epithelial cell (MEC) turnover and vascular function was quantified by quantitative reverse transcription PCR. Results demonstrated that omitting the dry period was possible in goats but was not as easy as claimed before. Renewal of MEC was suppressed in CL glands, which resulted in a smaller MEC population in the subsequent lactation. At the time of parturition (and throughout lactation), the mammary glands subjected to CL had smaller alveoli, more fully differentiated MEC, and a substantially larger capillary fraction compared with NL glands. The continuously lactating gland thus resembled a normally lactating gland in an advanced stage of lactation. None of the studied genomic factors could account for these treatment

  10. Hyperoxia decreases muscle glycogenolysis, lactate production, and lactate efflux during steady-state exercise.

    PubMed

    Stellingwerff, Trent; Leblanc, Paul J; Hollidge, Melanie G; Heigenhauser, George J F; Spriet, Lawrence L

    2006-06-01

    The aim of this study was to determine whether the decreased muscle and blood lactate during exercise with hyperoxia (60% inspired O2) vs. room air is due to decreased muscle glycogenolysis, leading to decreased pyruvate and lactate production and efflux. We measured pyruvate oxidation via PDH, muscle pyruvate and lactate accumulation, and lactate and pyruvate efflux to estimate total pyruvate and lactate production during exercise. We hypothesized that 60% O2 would decrease muscle glycogenolysis, resulting in decreased pyruvate and lactate contents, leading to decreased muscle pyruvate and lactate release with no change in PDH activity. Seven active male subjects cycled for 40 min at 70% VO2 peak on two occasions when breathing 21 or 60% O2. Arterial and femoral venous blood samples and blood flow measurements were obtained throughout exercise, and muscle biopsies were taken at rest and after 10, 20, and 40 min of exercise. Hyperoxia had no effect on leg O2 delivery, O2 uptake, or RQ during exercise. Muscle glycogenolysis was reduced by 16% with hyperoxia (267 +/- 19 vs. 317 +/- 21 mmol/kg dry wt), translating into a significant, 15% reduction in total pyruvate production over the 40-min exercise period. Decreased pyruvate production during hyperoxia had no effect on PDH activity (pyruvate oxidation) but significantly decreased lactate accumulation (60%: 22.6 +/- 6.4 vs. 21%: 31.3 +/- 8.7 mmol/kg dry wt), lactate efflux, and total lactate production over 40 min of cycling. Decreased glycogenolysis in hyperoxia was related to an approximately 44% lower epinephrine concentration and an attenuated accumulation of potent phosphorylase activators ADPf and AMPf during exercise. Greater phosphorylation potential during hyperoxia was related to a significantly diminished rate of PCr utilization. The tighter metabolic match between pyruvate production and oxidation resulted in a decrease in total lactate production and efflux over 40 min of exercise during hyperoxia.

  11. Hypoxia and exercise provoke both lactate release and lactate oxidation by the human brain.

    PubMed

    Overgaard, Morten; Rasmussen, Peter; Bohm, Aske M; Seifert, Thomas; Brassard, Patrice; Zaar, Morten; Homann, Pernille; Evans, Kevin A; Nielsen, Henning B; Secher, Niels H

    2012-07-01

    Lactate is shuttled between organs, as demonstrated in the Cori cycle. Although the brain releases lactate at rest, during physical exercise there is a cerebral uptake of lactate. Here, we evaluated the cerebral lactate uptake and release in hypoxia, during exercise and when the two interventions were combined. We measured cerebral lactate turnover via a tracer dilution method ([1-(13)C]lactate), using arterial to right internal jugular venous differences in 9 healthy individuals (5 males and 4 females), at rest and during 30 min of submaximal exercise in normoxia and hypoxia (F(i)o(2) 10%, arterial oxygen saturation 72 ± 10%, mean ± sd). Whole-body lactate turnover increased 3.5-fold and 9-fold at two workloads in normoxia and 18-fold during exercise in hypoxia. Although middle cerebral artery mean flow velocity increased during exercise in hypoxia, calculated cerebral mitochondrial oxygen tension decreased by 13 mmHg (P<0.001). At the same time, cerebral lactate release increased from 0.15 ± 0.1 to 0.8 ± 0.6 mmol min(-1) (P<0.05), corresponding to ∼10% of cerebral energy consumption. Concurrently, cerebral lactate uptake was 1.0 ± 0.9 mmol min(-1) (P<0.05), of which 57 ± 9% was oxidized, demonstrating that lactate oxidation may account for up to ∼33% of the energy substrate used by the brain. These results support the existence of a cell-cell lactate shuttle that may involve neurons and astrocytes.

  12. Non-thermal effects of a ceramics radiation on reversibility of lactate dehydrogenase reaction.

    PubMed

    Kohashi, M; Kasuya, Y; Watanabe, T

    1996-02-01

    Non-thermal effects of a ceramics radiation on reversibility of lactate dehydrogenase reaction have been investigated using the enzyme irradiated on cooling, and a pyruvate/NADH (system I) or a lactate/NAD+ (system II) as substrate. The Km for lactate in the system II using the irradiated enzyme tended to decrease just like balancing with the increase in Km for pyruvate in system I. The Vmax/Km for system II was increased 2.3-fold by the 18-h irradiated enzyme. Each enthalpy and entropy change in system II using the 18-h irradiation of the enzyme was decreased by 21 kJ mol-1, although that in system I was increased by 12 kJ mol-1. From a thermodynamic analysis, it was estimated that solvation of the active center of LDH was promoted and stabilized by the irradiation, and that it caused this regulation of the reversibility of LDH.

  13. Lactate production by the mammalian blastocyst: manipulating the microenvironment for uterine implantation and invasion?

    PubMed

    Gardner, David K

    2015-04-01

    The mammalian blastocyst exhibits a high capacity for aerobic glycolysis, a metabolic characteristic of tumours. It has been considered that aerobic glycolysis is a means to ensure a high carbon flux to fulfil biosynthetic demands. Here, alternative explanations for this pattern of metabolism are considered. Lactate creates a microenvironment of low pH around the embryo to assist the disaggregation of uterine tissues to facilitate trophoblast invasion. Further it is proposed that lactate acts as a signalling molecule (especially at the reduced oxygen tension present at implantation) to elicit bioactive VEGF recruitment from uterine cells, to promote angiogenesis. Finally it is suggested that the region of high lactate/low pH created by the blastocyst modulates the activity of the local immune response, helping to create immune tolerance. Consequently, the mammalian blastocyst offers a model to study the role of microenvironments, and how metabolites and pH are used in signalling.

  14. Neuroendocrine regulation of prolactin secretion during late pregnancy: easing the transition into lactation.

    PubMed

    Andrews, Z B

    2005-07-01

    Prolactin is an anterior pituitary hormone critical for maintaining pregnancy and lactation. Under normal conditions, prolactin secretion is tightly regulated by inhibitory dopaminergic neuronal systems within the mediobasal hypothalamus in a process known as short-loop negative feedback. This review focuses on neuroendocrine adaptations to prolactin negative feedback during late pregnancy. It is suggested that, in terms of prolactin regulation, late pregnancy is a transition period into lactation because many of the neuroendocrine adaptations promoting hyperprolactinemia in lactation develop during late pregnancy. As a consequence, the maternal brain is geared to provide unrestrained prolactin release critical for milk production, maternal care and thus survival of the offspring before parturition. The mechanisms responsible for these changes are discussed.

  15. The relationship between blood potassium, blood lactate, and electromyography signals related to fatigue in a progressive cycling exercise test.

    PubMed

    Tenan, Matthew S; McMurray, Robert G; Blackburn, B Troy; McGrath, Melanie; Leppert, Kyle

    2011-02-01

    Local muscle fatigue may be related to potassium efflux from the muscle cell and/or lactate accumulation within the muscle. Local fatigue causes a decrease in median frequency (MPF) of the electromyogram's power spectrum during isometric contractions but its relationship to changes in potassium and lactate during dynamic exercise is equivocal. Thus, this investigation evaluated relationships between changes in the MPF from the vastus lateralis and blood levels of lactate and potassium during an incremental cycling test and recovery. Trained cyclists (n=8) completed a discontinuous, graded cycle test to exhaustion under normal and glycogen-reduced conditions. The glycogen reduced condition promoted an environment of lower lactate production while permitting a consistent potassium response. Blood samples and maximal isometric EMG data were collected at the end of each stage and during recovery. Maximal lactate levels were ∼ 60% lower in the glycogen reduced condition; potassium was similar between trials. MPF did not change significantly at volitional fatigue. Further, MPF was not significantly related to lactate (p>0.27) or potassium (p>0.16) in either condition. Though both lactate and potassium have been implicated as factors relating to local muscle fatigue, neither is significantly related to changes in MPF during or after progressive exercise on a cycle ergometer.

  16. Lactate and force production in skeletal muscle

    PubMed Central

    Kristensen, Michael; Albertsen, Janni; Rentsch, Maria; Juel, Carsten

    2005-01-01

    Lactic acid accumulation is generally believed to be involved in muscle fatigue. However, one study reported that in rat soleus muscle (in vitro), with force depressed by high external K+ concentrations a subsequent incubation with lactic acid restores force and thereby protects against fatigue. However, incubation with 20 mm lactic acid reduces the pH gradient across the sarcolemma, whereas the gradient is increased during muscle activity. Furthermore, unlike active muscle the Na+–K+ pump is not activated. We therefore hypothesized that lactic acid does not protect against fatigue in active muscle. Three incubation solutions were used: 20 mm Na-lactate (which acidifies internal pH), 12 mm Na-lactate +8 mm lactic acid (which mimics the pH changes during muscle activity), and 20 mm lactic acid (which acidifies external pH more than internal pH). All three solutions improved force in K+-depressed rat soleus muscle. The pH regulation associated with lactate incubation accelerated the Na+–K+ pump. To study whether the protective effect of lactate/lactic acid is a general mechanism, we stimulated muscles to fatigue with and without pre-incubation. None of the incubation solutions improved force development in repetitively stimulated muscle (Na-lactate had a negative effect). It is concluded that although lactate/lactic acid incubation regains force in K+-depressed resting muscle, a similar incubation has no or a negative effect on force development in active muscle. It is suggested that the difference between the two situations is that lactate/lactic acid removes the negative consequences of an unusual large depolarization in the K+-treated passive muscle, whereas the depolarization is less pronounced in active muscle. PMID:15550457

  17. Lactate and force production in skeletal muscle.

    PubMed

    Kristensen, Michael; Albertsen, Janni; Rentsch, Maria; Juel, Carsten

    2005-01-15

    Lactic acid accumulation is generally believed to be involved in muscle fatigue. However, one study reported that in rat soleus muscle (in vitro), with force depressed by high external K(+) concentrations a subsequent incubation with lactic acid restores force and thereby protects against fatigue. However, incubation with 20 mm lactic acid reduces the pH gradient across the sarcolemma, whereas the gradient is increased during muscle activity. Furthermore, unlike active muscle the Na(+)-K(+) pump is not activated. We therefore hypothesized that lactic acid does not protect against fatigue in active muscle. Three incubation solutions were used: 20 mM Na-lactate (which acidifies internal pH), 12 mM Na-lactate +8 mm lactic acid (which mimics the pH changes during muscle activity), and 20 mM lactic acid (which acidifies external pH more than internal pH). All three solutions improved force in K(+)-depressed rat soleus muscle. The pH regulation associated with lactate incubation accelerated the Na(+)-K(+) pump. To study whether the protective effect of lactate/lactic acid is a general mechanism, we stimulated muscles to fatigue with and without pre-incubation. None of the incubation solutions improved force development in repetitively stimulated muscle (Na-lactate had a negative effect). It is concluded that although lactate/lactic acid incubation regains force in K(+)-depressed resting muscle, a similar incubation has no or a negative effect on force development in active muscle. It is suggested that the difference between the two situations is that lactate/lactic acid removes the negative consequences of an unusual large depolarization in the K(+)-treated passive muscle, whereas the depolarization is less pronounced in active muscle.

  18. Inhibition of lactate removal by ketone bodies in rat liver. Evidence for a quantitatively important role of the plasma membrane lactate transporter in lactate metabolism.

    PubMed Central

    Metcalfe, H K; Monson, J P; Welch, S G; Cohen, R D

    1986-01-01

    We studied the effect of DL-3-hydroxybutyrate and acetoacetate on lactate transport into isolated hepatocytes and on lactate removal in the isolated perfused rat liver. Ketone bodies inhibited lactate transport into isolated hepatocytes (maximum, 35% at concentrations of 10-20 mM). Lactate removal and glucose production by perfused livers were examined before and after the introduction of a constant infusion of hydroxybutyrate, acetoacetate, or appropriate control into the portal venous limb. Lactate removal was significantly inhibited within 10 s of the appearance of increasing concentrations of ketone bodies in the effluent. Corresponding decreases in glucose production were observed. The dependence of inhibition on D-3-hydroxybutyrate concentration was documented in isolated perfused livers (maximum inhibition of lactate removal, 58% at 14 mM). This phenomenon could be a factor in the development of lactic acidosis accompanying ketoacidosis, and indicates that plasma membrane lactate transport may determine the rate of hepatic lactate removal. PMID:3745435

  19. Low vitamin D status is associated with advanced liver fibrosis in patients with nonalcoholic fatty liver disease.

    PubMed

    Yang, Bing-Bing; Chen, Yuan-Hua; Zhang, Cheng; Shi, Chang-E; Hu, Kai-Feng; Zhou, Ju; Xu, De-Xiang; Chen, Xi

    2017-02-01

    Several studies explored the association between vitamin D status and nonalcoholic fatty liver disease with contradictory results. We aimed to investigate the association between vitamin D status, inflammatory cytokines and liver fibrosis in nonalcoholic fatty liver disease patients. Two hundred nineteen nonalcoholic fatty liver disease patients and 166 age- and gender- matched healthy controls were recruited for this study. Serum 25(OH)D was measured by radioimmunoassay. Serum interleukin-8 and transforming growth factor-β1 were measured using ELISA. Serum 25(OH)D was only marginally decreased in nonalcoholic fatty liver disease patients. Interestingly, serum 25(OH)D was markedly reduced in nonalcoholic fatty liver disease patients with advanced liver fibrosis compared to nonalcoholic fatty liver disease patients with indeterminate liver fibrosis and no advanced fibrosis. Logistic regression analysis showed that there was an inverse association between serum 25(OH)D and severity of liver fibrosis in nonalcoholic fatty liver disease patients. Further analysis showed that serum interleukin-8 was elevated in nonalcoholic fatty liver disease patients, the highest interleukin-8 in patients with advanced fibrosis. An inverse correlation between serum 25(OH)D and interleukin-8 was observed in nonalcoholic fatty liver disease patients with and without liver fibrosis. Although serum transforming growth factor-β1 was slightly elevated in nonalcoholic fatty liver disease patients, serum transforming growth factor-β1 was reduced in nonalcoholic fatty liver disease patients with advanced fibrosis. Unexpectedly, a positive correlation between serum 25(OH)D and transforming growth factor-β1 was observed in nonalcoholic fatty liver disease patients with advanced fibrosis. In conclusion, low vitamin D status is associated with advanced liver fibrosis in nonalcoholic fatty liver disease patients. Interleukin-8 may be an important mediator for hepatic fibrosis in nonalcoholic

  20. Glycolysis and the significance of lactate in traumatic brain injury

    PubMed Central

    Carpenter, Keri L. H.; Jalloh, Ibrahim; Hutchinson, Peter J.

    2015-01-01

    In traumatic brain injury (TBI) patients, elevation of the brain extracellular lactate concentration and the lactate/pyruvate ratio are well-recognized, and are associated statistically with unfavorable clinical outcome. Brain extracellular lactate was conventionally regarded as a waste product of glucose, when glucose is metabolized via glycolysis (Embden-Meyerhof-Parnas pathway) to pyruvate, followed by conversion to lactate by the action of lactate dehydrogenase, and export of lactate into the extracellular fluid. In TBI, glycolytic lactate is ascribed to hypoxia or mitochondrial dysfunction, although the precise nature of the latter is incompletely understood. Seemingly in contrast to lactate's association with unfavorable outcome is a growing body of evidence that lactate can be beneficial. The idea that the brain can utilize lactate by feeding into the tricarboxylic acid (TCA) cycle of neurons, first published two decades ago, has become known as the astrocyte-neuron lactate shuttle hypothesis. Direct evidence of brain utilization of lactate was first obtained 5 years ago in a cerebral microdialysis study in TBI patients, where administration of 13C-labeled lactate via the microdialysis catheter and simultaneous collection of the emerging microdialysates, with 13C NMR analysis, revealed 13C labeling in glutamine consistent with lactate utilization via the TCA cycle. This suggests that where neurons are too damaged to utilize the lactate produced from glucose by astrocytes, i.e., uncoupling of neuronal and glial metabolism, high extracellular levels of lactate would accumulate, explaining the association between high lactate and poor outcome. Recently, an intravenous exogenous lactate supplementation study in TBI patients revealed evidence for a beneficial effect judged by surrogate endpoints. Here we review the current state of knowledge about glycolysis and lactate in TBI, how it can be measured in patients, and whether it can be modulated to achieve better

  1. Lactate receptor sites link neurotransmission, neurovascular coupling, and brain energy metabolism.

    PubMed

    Lauritzen, Knut H; Morland, Cecilie; Puchades, Maja; Holm-Hansen, Signe; Hagelin, Else Marie; Lauritzen, Fredrik; Attramadal, Håvard; Storm-Mathisen, Jon; Gjedde, Albert; Bergersen, Linda H

    2014-10-01

    The G-protein-coupled lactate receptor, GPR81 (HCA1), is known to promote lipid storage in adipocytes by downregulating cAMP levels. Here, we show that GPR81 is also present in the mammalian brain, including regions of the cerebral neocortex and hippocampus, where it can be activated by physiological concentrations of lactate and by the specific GPR81 agonist 3,5-dihydroxybenzoate to reduce cAMP. Cerebral GPR81 is concentrated on the synaptic membranes of excitatory synapses, with a postsynaptic predominance. GPR81 is also enriched at the blood-brain-barrier: the GPR81 densities at endothelial cell membranes are about twice the GPR81 density at membranes of perivascular astrocytic processes, but about one-seventh of that on synaptic membranes. There is only a slight signal in perisynaptic processes of astrocytes. In synaptic spines, as well as in adipocytes, GPR81 immunoreactivity is located on subplasmalemmal vesicular organelles, suggesting trafficking of the protein to and from the plasma membrane. The results indicate roles of lactate in brain signaling, including a neuronal glucose and glycogen saving response to the supply of lactate. We propose that lactate, through activation of GPR81 receptors, can act as a volume transmitter that links neuronal activity, cerebral energy metabolism and energy substrate availability. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Staphylococcus aureus lactate- and malate-quinone oxidoreductases contribute to nitric oxide resistance and virulence.

    PubMed

    Spahich, Nicole A; Vitko, Nicholas P; Thurlow, Lance R; Temple, Brenda; Richardson, Anthony R

    2016-06-01

    Staphylococcus aureus is a Gram-positive pathogen that resists many facets of innate immunity including nitric oxide (NO·). Staphylococcus aureus NO-resistance stems from its ability to evoke a metabolic state that circumvents the negative effects of reactive nitrogen species. The combination of l-lactate and peptides promotes S. aureus growth at moderate NO-levels, however, neither nutrient alone suffices. Here, we investigate the staphylococcal malate-quinone and l-lactate-quinone oxidoreductases (Mqo and Lqo), both of which are critical during NO-stress for the combined utilization of peptides and l-lactate. We address the specific contributions of Lqo-mediated l-lactate utilization and Mqo-dependent amino acid consumption during NO-stress. We show that Lqo conversion of l-lactate to pyruvate is required for the formation of ATP, an essential energy source for peptide utilization. Thus, both Lqo and Mqo are essential for growth under these conditions making them attractive candidates for targeted therapeutics. Accordingly, we exploited a modelled Mqo/Lqo structure to define the catalytic and substrate-binding residues.We also compare the S. aureus Mqo/Lqo enzymes to their close relatives throughout the staphylococci and explore the substrate specificities of each enzyme. This study provides the initial characterization of the mechanism of action and the immunometabolic roles for a newly defined staphylococcal enzyme family. © 2016 John Wiley & Sons Ltd.

  3. Lactate Activates HIF-1 in Oxidative but Not in Warburg-Phenotype Human Tumor Cells

    PubMed Central

    De Saedeleer, Christophe J.; Copetti, Tamara; Porporato, Paolo E.; Verrax, Julien

    2012-01-01

    Cancer can be envisioned as a metabolic disease driven by pressure selection and intercellular cooperativeness. Together with anaerobic glycolysis, the Warburg effect, formally corresponding to uncoupling glycolysis from oxidative phosphorylation, directly participates in cancer aggressiveness, supporting both tumor progression and dissemination. The transcription factor hypoxia-inducible factor-1 (HIF-1) is a key contributor to glycolysis. It stimulates the expression of glycolytic transporters and enzymes supporting high rate of glycolysis. In this study, we addressed the reverse possibility of a metabolic control of HIF-1 in tumor cells. We report that lactate, the end-product of glycolysis, inhibits prolylhydroxylase 2 activity and activates HIF-1 in normoxic oxidative tumor cells but not in Warburg-phenotype tumor cells which also expressed lower basal levels of HIF-1α. These data were confirmed using genotypically matched oxidative and mitochondria-depleted glycolytic tumor cells as well as several different wild-type human tumor cell lines of either metabolic phenotype. Lactate activates HIF-1 and triggers tumor angiogenesis and tumor growth in vivo, an activity that we found to be under the specific upstream control of the lactate transporter monocarboxylate transporter 1 (MCT1) expressed in tumor cells. Because MCT1 also gates lactate-fueled tumor cell respiration and mediates pro-angiogenic lactate signaling in endothelial cells, MCT1 inhibition is confirmed as an attractive anticancer strategy in which a single drug may target multiple tumor-promoting pathways. PMID:23082126

  4. Modulation of Mammary Stromal Cell Lactate Dynamics by Ambient Glucose and Epithelial Factors.

    PubMed

    Tobar, Nicolas; Porras, Omar; Smith, Patricio C; Barros, L Felipe; Martínez, Jorge

    2017-01-01

    Hyperglycemia is a risk factor for a variety of human cancers. Increased access to glucose and that tumor metabolize glucose by a glycolytic process even in the presence of oxygen (Warburg effect), provide a framework to analyze a particular set of metabolic adaptation mechanisms that may explain this phenomenon. In the present work, using a mammary stromal cell line derived from healthy tissue that was subjected to a long-term culture in low (5 mM) or high (25 mM) glucose, we analyzed kinetic parameters of lactate transport using a FRET biosensor. Our results indicate that the glucose pre-culture and soluble epithelial factors constitute a stimulus for lactate stromal production, factors that also modify the kinetic parameters and the monocarboxylate transporters expression in stromal cells. We also observed a vectorial flux of lactate from stroma to epithelial cells in a co-culture setting and found that the uptake of lactate by epithelial cells correlates with the degree of malignancy. Glucose preconditioning of the stromal cell stimulated epithelial motility. Our findings suggest that lactate generated by stromal cells in the high glucose condition stimulate epithelial migration. Overall, our results support the notion that glucose not only provides a substrate for tumor nutrition but also behaves as a signal promoting malignancy. J. Cell. Physiol. 232: 136-144, 2017. © 2016 Wiley Periodicals, Inc.

  5. Treatment of fibrosis in nonalcoholic fatty liver disease.

    PubMed

    Hoteit, Maarouf A; Anania, Frank A

    2007-03-01

    Nonalcoholic steatohepatitis (NASH) is one of the most common liver disorders in North America. The mechanism of liver injury in NASH involves insulin resistance and oxidative stress as well as cytokine release. Therapeutic interventions aimed at enhancing insulin sensitivity or reducing oxidative stress have been studied. The role of peptide hormones secreted by adipose tissue--adipocytokines--in the potential pathogenesis of NASH is an area of intense research. As the function of adipokines in modulating hepatic inflammation and fibrosis is elucidated, the potential for novel treatment strategies in patients with NASH is likely to be realized.

  6. Clinical Presentation and Patient Evaluation in Nonalcoholic Fatty Liver Disease.

    PubMed

    Patel, Vaishali; Sanyal, Arun J; Sterling, Richard

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is a diagnosis of exclusion. Most patients are asymptomatic and diagnosed incidentally. Most patients remain undiagnosed. A high index of suspicion and serologic work-up to rule out alternative causes of liver disease is required. In NALFD, fibrosis correlates with outcomes, including mortality. To diagnose, assess severity, and monitor fibrosis, 2 noninvasive methods can be used. However, noninvasive tests are more helpful at extremes of fibrosis: excluding it or diagnosing advanced fibrosis. Liver biopsy is usually reserved for cases whereby noninvasive tests fail to accurately determine the degree of fibrosis or the diagnosis is unclear.

  7. Non-alcoholic fatty liver disease in children.

    PubMed

    Janczyk, Wojciech; Socha, Piotr

    2012-06-01

    Non-alcoholic fatty liver disease is increasingly prevalent in children, together with obesity. Transaminases, tests for insulin resistance, ultrasonography and MRI are variably used as surrogates markers of steatosis. Other liver diseases, such as Wilson disease, should be excluded. A liver biopsy is performed in selected cases: young children, familial history of severe disease, inconclusive tests for other pathologies, suspected advanced fibrosis, hypertransaminasemia despite weight loss and in clinical trials. Weight reduction, and changes in lifestyle, are the front-line treatment. Drug therapy is under evaluation. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  8. Nonalcoholic Fatty liver disease, diabetes, obesity, and hepatocellular carcinoma.

    PubMed

    Noureddin, Mazen; Rinella, Mary E

    2015-05-01

    Diabetes and obesity are associated with nonalcoholic fatty liver disease (NAFLD) and an increased incidence of hepatocellular carcinoma (HCC). NAFLD is the commonest cause of chronic liver disease. HCC can develop in NAFLD patients even without cirrhosis, suggesting an association between the metabolic process and HCC and raising a concern that many cancers could be missed given high NAFLD prevalence and screening limitations. The increasing prevalence of these conditions and lack of effective treatments necessitate a better understanding of their connection. This article defines the known interrelationships and common pathways between NAFLD, diabetes, obesity and HCC and possible chemoprevention strategies. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. New therapeutic perspectives in non-alcoholic steatohepatitis.

    PubMed

    Ampuero, Javier; Sánchez-Torrijos, Yolanda; Aguilera, Virginia; Bellido, Francisco; Romero-Gómez, Manuel

    2017-09-02

    Management of non-alcoholic steatohepatitis is focused on restitution of metabolic derangement, weight loss and drugs able to improve steatosis, ballooning and fibrosis. Life-style interventions based on Mediterranean diet and increasing physical activity are the first line therapy. In patients with unsuccessful life-style intervention several drugs are under development: agonist PPAR, agonist GLP-1R and agonist FXR together with drugs focussing on inflammation, ballooning, apoptosis and fibrosis. Bariatric surgery or advanced endoscopy are reserved for morbid obese without response to life-style intervention and weighting loss drugs. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  10. [Consequences of non-alcoholic fatty liver disease still unclear].

    PubMed

    Jansen, Peter L M

    2012-01-01

    There is still a lack of clarity concerning the long-term outcome and severity of non-alcoholic fatty liver disease (NAFLD). Results of a study recently conducted by the National Health and Nutrition Examination Survey (NHANES) showed that patients with NAFLD diagnosed 30 years ago did not experience decreased survival when compared with persons without NAFLD. But questions arise about the diagnostic methods in this study and the consequences for daily practice. Is NAFLD really a disease, and what is the diagnostic method of choice?

  11. Update on Berberine in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Liu, Yang; Zhang, Li; Song, Haiyan

    2013-01-01

    Berberine (BBR), an active ingredient from nature plants, has demonstrated multiple biological activities and pharmacological effects in a series of metabolic diseases including nonalcoholic fatty liver disease (NAFLD). The recent literature points out that BBR may be a potential drug for NAFLD in both experimental models and clinical trials. This review highlights important discoveries of BBR in this increasing disease and addresses the relevant targets of BBR on NAFLD which links to insulin pathway, adenosine monophosphate-activated protein kinase (AMPK) signaling, gut environment, hepatic lipid transportation, among others. Developing nuanced understanding of the mechanisms will help to optimize more targeted and effective clinical application of BBR for NAFLD. PMID:23843872

  12. Methylprednisolone improves lactate metabolism through reduction of elevated serum lactate in rat model of multiple sclerosis.

    PubMed

    Ghareghani, Majid; Ghanbari, Amir; Dokoohaki, Shima; Farhadi, Naser; Hosseini, Seyed Mojtaba; Mohammadi, Reza; Sadeghi, Heibatollah

    2016-12-01

    Some studies have demonstrated elevated concentrations of lactate both in the cerebrospinal fluid (CSF) and blood samples of multiple sclerosis (MS) patients as a pathological condition. We designed an experimental study first to investigate the serum level of lactate as a biomarker of MS progression and also to investigate the effect of methylprednisolone on serum lactate. Experimental autoimmune encephalomyelitis (EAE) was inducted in Lewis rats, and then rats were treated intraperitoneally with methylprednisolone (30mg/kg/d), at the disease onset, and the clinical scores were recorded. After seven days of treatment, the serum levels of lactate were determined using high performance liquid chromatography (HPLC). Moreover, lymphocyte infiltration and the demyelinated area was analysed in spinal cord. Compared to the untreated-EAE rats, methylprednisolone remarkably improved the clinical score of EAE and ameliorated the spinal cord inflammation and demyelination. In addition, the marked decline in IFN-γ and the increase in IL-4 confirmed improvement in the rats treated with methylprednisolone. Measurement of lactate using HPLC indicated enhancement in the serum level of lactate in the untreated-EAE rats; the lactate level significantly decreased after methylprednisolone therapy. Moreover, serum lactates and disease severity were correlated positively and significantly. These data confirmed for the first time, that methylprednisolone can decreases the enhanced level of serum lactate in EAE model. In addition, it was shown that measurement of serum lactate could be an inexpensive and accurate laboratory test to determine the response to treatment and to assess disease severity in MS patients. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. [Interference of ethylene glycol on lactate assays].

    PubMed

    Graïne, H; Toumi, K; Roullier, V; Capeau, J; Lefèvre, G

    2007-01-01

    Ethylene glycol is broken down to three main organic acids: glycolic acid, glyoxylic acid and oxalic acid which cause severe metabolic acidosis. Effect of these three acids on lactate assays was evaluated in five blood gas analysers and two clinical chemistry analysers. For all systems, no influence of oxalic acid on lactate results could be demonstrated. No interference of glycolic acid could be observed on lactate assay performed with Rapid Lab 1265 (R: 104,9 +/- 12,1%), Vitros 950 (R: 105,7 +/- 5,3 %) and Architect ci8200 (R: 104,9 +/- 4,7%), but on the contrary, CCX 4, OMNI S, ABL 725 and 825 demonstrated a concentration-dependent interference. No interference of glyoxylic acid could be observed with Vitros 950, but a positive interference could be observed with ABL 725 and 825, OMNI S, CCX4 and Architect ci8200 A linear relationship between apparent lactate concentration found with ABL 725 and 825, OMNI S, CCX 4, and glyoxylic acid could be observed (0,94 < r < 0,99), a weaker interference being observed with Rapid Lab 1265 and Architect ci 8200. Our results demonstrated that in case of ethylene glycol poisoning, cautious interpretation of lactate assay should be done, since wrong results of lactacidemia could lead to misdiagnostic and delay patient treatment.

  14. The Clinical Significance of Elevated Blood Lactate

    PubMed Central

    Phillipson, Eliot A.; Sproule, Brian J.

    1965-01-01

    Three patients with elevated blood lactate values are described. The first, despite moderate hyperlactatemia of 5.3 mEq./1. and severe acidosis with an arterial blood pH of 6.98, had no “excess lactate”. In a second patient, moderate acidosis with a pH of 7.27 and blood lactate of 7.5 mEq./1., of which 33% was excess lactate, was found to be secondary to tissue hypoxia on an ischemic basis and preceded the onset of clinical shock by four hours. A third patient, diabetic and under treatment with phenformin hydrochloride, presented with many features suggestive of pulmonary embolism, including marked pulmonary hypertension. A diagnosis of idiopathic lactic acidosis was established when the arterial blood pH was found to be 6.77 and a blood lactate value of 14.2 mEq./1., 60% as excess lactate, was discovered in the absence of a demonstrable cause of tissue hypoxia. Exploration of the pulmonary vascular bed showed no sign of mechanical blockage. The diagnostic, therapeutic and prognostic value of measuring blood lactic acid, and of quantitating the proportion circulating as “excess lactate”, is emphasized. PMID:14312443

  15. Lactate metabolism during exercise in patients with mitochondrial myopathy.

    PubMed

    Jeppesen, Tina D; Orngreen, Mette C; Van Hall, Gerrit; Vissing, John

    2013-08-01

    Patients with mitochondrial DNA mutations often have elevated plasma lactate at rest and during exercise, but it is unknown whether the high lactate levels are caused by a high production, an impaired oxidation or a combination. We studied lactate kinetics in 10 patients with mtDNA mutations and 10 matched healthy control subjects at rest and during cycle exercise with a combination of femoral arterio-venous differences of lactate, and lactate tracer dilution methodology. During exercise, lactate concentration and production rates were several-fold higher in patients, but despite mitochondrial dysfunction, lactate was oxidized in muscle to the same extent as in healthy control subjects. This surprisingly high ability to burn lactate in working muscle with defective mitochondria, probably relates to the variability of oxidative capacity among muscle fibers. The data suggests that lactate is not solely an indicator of impaired oxidative capacity, but an important fuel for oxidative metabolism, even in muscle with severely impaired mitochondrial function.

  16. The association of vitamin D deficiency with non-alcoholic fatty liver disease

    PubMed Central

    Küçükazman, Metin; Ata, Naim; Dal, Kürşat; Yeniova, Abdullah Özgür; Kefeli, Ayşe; Basyigit, Sebahat; Aktas, Bora; Akin, Kadir Okhan; Ağladioğlu, Kadir; Üre, Öznur Sari; Topal, Firdes; Nazligül, Yaşar; Beyan, Esin; Ertugrul, Derun Taner

    2014-01-01

    OBJECTIVE: Vitamin D deficiency has been related to diabetes, hypertension, hyperlipidemia and peripheral vascular disease. In this study, we aimed to investigate the role of vitamin D status in non-alcoholic fatty liver disease. METHODS: We included 211 consecutive subjects to examine the presence of non-alcoholic fatty liver disease. Of these subjects, 57 did not have non-alcoholic fatty liver disease and 154 had non-alcoholic fatty liver disease. RESULTS: The non-alcoholic fatty liver disease group had significantly higher fasting blood glucose (p = 0.005), uric acid (p = 0.001), aspartate aminotransferase (p<0.001), alanine aminotransferase (p<0.001), γ-glutamyltransferase (p<0.0001), alkaline phosphatase (p = 0.028), HbA1c (p<0.001), ferritin (p<0.001), insulin (p = 0.016), C-peptide (p = 0.001), HOMA-IR (p = 0.003), total cholesterol (p = 0.001), triglyceride (p = 0.001) and white blood cell (p = 0.04) levels. In contrast, the non-alcoholic fatty liver disease group had significantly lower 25(OH)D levels (12.3±8.9 ng/dl, p<0.001) compared with those of the control group (20±13.6 ng/dl). CONCLUSIONS: In this study, we found lower serum 25(OH)D levels in patients with non-alcoholic fatty liver disease than in subjects without non-alcoholic fatty liver disease. To establish causality between vitamin D and non-alcoholic fatty liver disease, further interventional studies with a long-term follow-up are needed. PMID:25141113

  17. Interleukin-1 and inflammasomes in alcoholic liver disease/acute alcoholic hepatitis and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    PubMed

    Tilg, Herbert; Moschen, Alexander R; Szabo, Gyongyi

    2016-09-01

    Both alcoholic liver disease (ALD) and nonalcoholic fatty liver disease are characterized by massive lipid accumulation in the liver accompanied by inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma in a substantial subgroup of patients. At several stages in these diseases, mediators of the immune system, such as cytokines or inflammasomes, are crucially involved. In ALD, chronic ethanol exposure sensitizes Kupffer cells to activation by lipopolysaccharides through Toll-like receptors, e.g., Toll-like receptor 4. This sensitization enhances the production of various proinflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-alpha, thereby contributing to hepatocyte dysfunction, necrosis, and apoptosis and the generation of extracellular matrix proteins leading to fibrosis/cirrhosis. Indeed, neutralization of IL-1 by IL-1 receptor antagonist has recently been shown to potently prevent liver injury in murine models of ALD. As IL-1 is clearly linked to key clinical symptoms of acute alcoholic hepatitis such as fever, neutrophilia, and wasting, interfering with the IL-1 pathway might be an attractive treatment strategy in the future. An important role for IL-1-type cytokines and certain inflammasomes has also been demonstrated in murine models of nonalcoholic fatty liver disease. IL-1-type cytokines can regulate hepatic steatosis; the NLR family pyrin domain containing 3 inflammasome is critically involved in metabolic dysregulation. IL-1 cytokine family members and various inflammasomes mediate different aspects of both ALD and nonalcoholic fatty liver disease. (Hepatology 2016;64:955-965). © 2016 by the American Association for the Study of Liver Diseases.

  18. Cumulative lactate and hospital mortality in ICU patients

    PubMed Central

    2013-01-01

    Background Both hyperlactatemia and persistence of hyperlactatemia have been associated with bad outcome. We compared lactate and lactate-derived variables in outcome prediction. Methods Retrospective observational study. Case records from 2,251 consecutive intensive care unit (ICU) patients admitted between 2001 and 2007 were analyzed. Baseline characteristics, all lactate measurements, and in-hospital mortality were recorded. The time integral of arterial blood lactate levels above the upper normal threshold of 2.2 mmol/L (lactate-time-integral), maximum lactate (max-lactate), and time-to-first-normalization were calculated. Survivors and nonsurvivors were compared and receiver operating characteristic (ROC) analysis were applied. Results A total of 20,755 lactate measurements were analyzed. Data are srpehown as median [interquartile range]. In nonsurvivors (n = 405) lactate-time-integral (192 [0–1881] min·mmol/L) and time-to-first normalization (44.0 [0–427] min) were higher than in hospital survivors (n = 1846; 0 [0–134] min·mmol/L and 0 [0–75] min, respectively; all p < 0.001). Normalization of lactate <6 hours after ICU admission revealed better survival compared with normalization of lactate >6 hours (mortality 16.6% vs. 24.4%; p < 0.001). AUC of ROC curves to predict in-hospital mortality was the largest for max-lactate, whereas it was not different among all other lactate derived variables (all p > 0.05). The area under the ROC curves for admission lactate and lactate-time-integral was not different (p = 0.36). Conclusions Hyperlactatemia is associated with in-hospital mortality in a heterogeneous ICU population. In our patients, lactate peak values predicted in-hospital mortality equally well as lactate-time-integral of arterial blood lactate levels above the upper normal threshold. PMID:23446002

  19. Early lactation production, health, and welfare characteristics of cows selected for extended lactation.

    PubMed

    Lehmann, J O; Mogensen, L; Kristensen, T

    2017-02-01

    Some cows are able to achieve relatively high milk yields during extended lactations beyond 305 d in milk, and farmers may be able to use this potential by selecting the most suitable cows for an extended lactation. However, the decision to postpone insemination has to rely on information available in early lactation. The main objectives of this study were, therefore, to assess the association between the information available in early lactation and the relative milk production of cows on extended lactation, and to investigate if this information can be used to differentiate time of first insemination between cows. Data came from 4 Danish private herds practicing extended lactation in which some cows are selected to have a delayed time of planned first insemination. Average herd size varied from 93 to 157 cows, and milk yield varied from 7,842 to 12,315 kg of energy-corrected milk (ECM) per cow per year across herds. The analysis was based on 422 completed extended lactations (427 ± 87 d), and each lactation was assigned to 1 of 3 (low, medium, and high) milk performance groups (MPG) within parity group within herd based on a standardized lactation yield. For cows in the high MPG, peak ECM yield, and ECM yield at dry off were significantly greater, the relative reduction in milk yield between 60 and 305 d in milk was significantly smaller, and a smaller proportion had a body condition score (scale: 1-5) at dry off of 3.5 or greater compared with cows in low MPG. Previous lactation days in milk at peak ECM yield and ECM yield at dry off were higher, the relative reduction in milk yield between 60 and 305 d in milk was smaller, and the number of inseminations per conception was higher for multiparous cows in high MPG compared with low. Current lactation ECM yield at second and third milk recording were greater for cows in high MPG compared with low. A principal component analysis indicated that variables related to fertility, diseases, and milk yield explained most

  20. Breast infections in non-lactating women.

    PubMed

    Abdelhadi, Maha S A; Bukharie, Huda A

    2005-09-01

    Breast infection in lactating mothers is a common entity which in the majority of cases can be explained by ascending infections. However, it has been noticed that the number of non lactating women presenting with breast abscesses is rising. This study attempts to explore the sensitivity pattern of organisms and underlying cause of breast infections in non-lactating women. This review was undertaken at King Fahd of the University, Alkhobar, Saudi Arabia between 1991-2003. All patients presenting with breast infections were included. Medical records, operative notes, cultures, histopathology reports and outcome were reviewed. The number of patients presenting with breast infections accounted for 179(3.5%) out of the total number of patients 6314 with variable breast complaints. Infection occurred in 136(76%) lactating women (Group I) ,while Non lactating (Group II) breast infections accounted for 43(24%). Age ranged from 24 years to 52 years. Underlying clinical conditions were found in 26 patients(60%) in Group II namely granulomatous mastitis13(50%), duct ectasia4 (15.3%), pregnancy3(11.5%), fat necrosis1(3.8%), diabetes3 (11.5%) and breast cancer 2(7.6%). The pattern of culture results was different in the two groups, from differing causative organisms namely staphylococcus aureus as the commonest organism in both groups, in comparison to such uncommon organisms as Klebsiella pneumonae, Peptococcus magnus, Streptococcus group B, Entro-bacter cloacae, Methicillin resistant staphylococcus aureus (MRSA) and Mycobacterium tuberculosis occurring in group II only. Fortunately, all organisms were sensitive to antimicrobial therapy. Breast infection in non-lactating women is an infrequent but recognized clinical entity that deserves special attention. An underlying clinical condition should always be sought and treated. Indeed, in addition to cultures, radiological modalities such as ultrasonographic imaging may provide specific diagnosis and aid the management.

  1. BREAST INFECTIONS IN NON-LACTATING WOMEN

    PubMed Central

    AbdelHadi, Maha S.A; Bukharie, Huda A.

    2005-01-01

    Background: Breast infection in lactating mothers is a common entity which in the majority of cases can be explained by ascending infections. However, it has been noticed that the number of non lactating women presenting with breast abscesses is rising. This study attempts to explore the sensitivity pattern of organisms and underlying cause of breast infections in non-lactating women. Materials and Methods: This review was undertaken at King Fahd of the University, Alkhobar, Saudi Arabia between 1991-2003. All patients presenting with breast infections were included. Medical records, operative notes, cultures, histopathology reports and outcome were reviewed. Results: The number of patients presenting with breast infections accounted for 179(3.5%) out of the total number of patients 6314 with variable breast complaints. Infection occurred in 136(76%) lactating women (Group I) ,while Non lactating (Group II) breast infections accounted for 43(24%). Age ranged from 24 years to 52 years. Underlying clinical conditions were found in 26 patients(60%) in Group II namely granulomatous mastitis13(50%), duct ectasia4 (15.3%), pregnancy3(11.5%), fat necrosis1(3.8%), diabetes3 (11.5%) and breast cancer 2(7.6%). The pattern of culture results was different in the two groups, from differing causative organisms namely staphylococcus aureus as the commonest organism in both groups, in comparison to such uncommon organisms as Klebsiella pneumonae, Peptococcus magnus, Streptococcus group B, Entro-bacter cloacae, Methicillin resistant staphylococcus aureus (MRSA) and Mycobacterium tuberculosis occurring in group II only. Fortunately, all organisms were sensitive to antimicrobial therapy. Conclusion: Breast infection in non-lactating women is an infrequent but recognized clinical entity that deserves special attention. An underlying clinical condition should always be sought and treated. Indeed, in addition to cultures, radiological modalities such as ultrasonographic imaging may

  2. Potential Epigenetic Mechanism in Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Sun, Chao; Fan, Jian-Gao; Qiao, Liang

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation in the liver. It ranges from simple steatosis to its more aggressive form, non-alcoholic steatohepatitis (NASH), which may develop into hepatic fibrosis, cirrhosis, or hepatocellular carcinoma (HCC) if it persists for a long time. However, the exact pathogenesis of NAFLD and the related metabolic disorders remain unclear. Epigenetic changes are stable alterations that take place at the transcriptional level without altering the underlying DNA sequence. DNA methylation, histone modifications and microRNA are among the most common forms of epigenetic modification. Epigenetic alterations are involved in the regulation of hepatic lipid metabolism, insulin resistance, mitochondrial damage, oxidative stress response, and the release of inflammatory cytokines, all of which have been implicated in the development and progression of NAFLD. This review summarizes the current advances in the potential epigenetic mechanism of NAFLD. Elucidation of epigenetic factors may facilitate the identification of early diagnositic biomarkers and development of therapeutic strategies for NAFLD. PMID:25751727

  3. The Natural Course of Non-Alcoholic Fatty Liver Disease.

    PubMed

    Calzadilla Bertot, Luis; Adams, Leon Anton

    2016-05-20

    Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, paralleling the epidemic of obesity and Type 2 diabetes mellitus (T2DM). NAFLD exhibits a histological spectrum, ranging from "bland steatosis" to the more aggressive necro-inflammatory form, non-alcoholic steatohepatitis (NASH) which may accumulate fibrosis to result in cirrhosis. Emerging data suggests fibrosis, rather than NASH per se, to be the most important histological predictor of liver and non-liver related death. Nevertheless, only a small proportion of individuals develop cirrhosis, however the large proportion of the population affected by NAFLD has led to predictions that NAFLD will become a leading cause of end stage liver disease, hepatocellular carcinoma (HCC), and indication for liver transplantation. HCC may arise in non-cirrhotic liver in the setting of NAFLD and is associated with the presence of the metabolic syndrome (MetS) and male gender. The MetS and its components also play a key role in the histological progression of NAFLD, however other genetic and environmental factors may also influence the natural history. The importance of NAFLD in terms of overall survival extends beyond the liver where cardiovascular disease and malignancy represents additional important causes of death.

  4. Taurine and tea polyphenols combination ameliorate nonalcoholic steatohepatitis in rats.

    PubMed

    Zhu, Wenhua; Chen, Siwen; Chen, Ronggui; Peng, Zhiqing; Wan, Jun; Wu, Benyan

    2017-09-08

    Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease, for which there is currently no safe and effective drug for therapy. In this study, we explored the effects of taurine, tea polyphenols (TPs), or a combination thereof, on NASH rats. Rats were divided into a normal group, a high-fat diet induced model group and a treatment group (including taurine, TPs, or taurine + TPs treatment for 8 weeks). Twelve weeks later, all rats were sacrificed, and serum transaminase, lipid and lipopolysaccharide levels and hepatic oxidative stress levels were determined. Histological changes were evaluated. In NASH rats, hepatocyte damage, lipid disturbance, oxidative stress and elevated lipopolysaccharide levels were confirmed. Taurine treatment alleviated hepatocyte damage and oxidative stress. TPs treatment improved lipid metabolism and increased hepatic antioxidant activity. The therapeutic effects of taurine + TPs treatment on hepatocyte damage, lipid disturbance, and oxidative stress were superior to those of taurine and TPs treatment, respectively. Taurine, TPs and their combination all decreased serum lipopolysaccharide levels in NASH rats, but the combination of the compounds caused these levels to decrease more significantly than taurine or TPs treatment alone. Taurine combined with TPs treatment could relieve NASH by alleviating hepatocyte damage, decreasing oxidative stress and improving lipid metabolism and gut flora disturbance partly. Taurine and TPs combination may act as a new effective medicine for treating NASH patients.

  5. A Model of Insulin Resistance and Nonalcoholic Steatohepatitis in Rats

    PubMed Central

    Svegliati-Baroni, Gianluca; Candelaresi, Cinzia; Saccomanno, Stefania; Ferretti, Gianna; Bachetti, Tiziana; Marzioni, Marco; De Minicis, Samuele; Nobili, Liliana; Salzano, Renata; Omenetti, Alessia; Pacetti, Deborah; Sigmund, Soeren; Benedetti, Antonio; Casini, Alessandro

    2006-01-01

    Insulin resistance induces nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH). We used a high-fat, high-calorie solid diet (HFD) to create a model of insulin resistance and NASH in nongenetically modified rats and to study the relationship between visceral adipose tissue and liver. Obesity and insulin resistance occurred in HFD rats, accompanied by a progressive increase in visceral adipose tissue tumor necrosis factor (TNF)-α mRNA and in circulating free fatty acids. HFD also decreased adiponectin mRNA and peroxisome proliferator-activated receptor (PPAR)-α expression in the visceral adipose tissue and the liver, respectively, and induced hepatic insulin resistance through TNF-α-mediated c-Jun N-terminal kinase (JNK)-dependent insulin receptor substrate-1Ser307 phosphorylation. These modifications lead to hepatic steatosis accompanied by oxidative stress phenomena, necroinflammation, and hepatocyte apoptosis at 4 weeks and by pericentral fibrosis at 6 months. Supplementation of n-3 polyunsaturated fatty acid, a PPARα ligand, to HFD-treated animals restored hepatic adiponectin and PPARα expression, reduced TNF-α hepatic levels, and ameliorated fatty liver and the degree of liver injury. Thus, our model mimics the most common features of NASH in humans and provides an ideal tool to study the role of individual pathogenetic events (as for PPARα down-regulation) and to define any future experimental therapy, such as n-3 polyunsaturated fatty acid, which ameliorated the degree of liver injury. PMID:16936261

  6. Role of Alcohol Metabolism in Non-Alcoholic Steatohepatitis

    PubMed Central

    Baker, Susan S.; Baker, Robert D.; Liu, Wensheng; Nowak, Norma J.; Zhu, Lixin

    2010-01-01

    Background Non-alcoholic steatohepatitis (NASH) is a serious form of non-alcoholic fatty liver disease (NAFLD), associated with obesity and insulin resistance. Previous studies suggested that intestinal bacteria produced more alcohol in obese mice than lean animals. Methodology/Principal Findings To investigate whether alcohol is involved in the pathogenesis of NASH, the expression of inflammation, fibrosis and alcohol metabolism related genes in the liver tissues of NASH patients and normal controls (NCs) were examined by microarray (NASH, n = 7; NC, n = 4) and quantitative real-time PCR (NASH, n = 6; NC, n = 6). Genes related to liver inflammation and fibrosis were found to be elevated in NASH livers compared to normal livers. The most striking finding is the increased gene transcription of alcohol dehydrogenase (ADH) genes, genes for catalase and cytochrome P450 2E1, and aldehyde dehydrogenase genes. Immunoblot analysis confirmed the increased expression of ADH1 and ADH4 in NASH livers (NASH, n = 9; NC, n = 4). Conclusions/Significance The augmented activity of all the available genes of the pathways for alcohol catabolism suggest that 1) alcohol concentration was elevated in the circulation of NASH patients; 2) there was a high priority for the NASH livers to scavenge alcohol from the circulation. Our data is the first human evidence that suggests alcohol may contribute to the development of NAFLD. PMID:20221393

  7. Exploring the metabolic syndrome: Nonalcoholic fatty pancreas disease

    PubMed Central

    Catanzaro, Roberto; Cuffari, Biagio; Italia, Angelo; Marotta, Francesco

    2016-01-01

    After the first description of fatty pancreas in 1933, the effects of pancreatic steatosis have been poorly investigated, compared with that of the liver. However, the interest of research is increasing. Fat accumulation, associated with obesity and the metabolic syndrome (MetS), has been defined as “fatty infiltration” or “nonalcoholic fatty pancreas disease” (NAFPD). The term “fatty replacement” describes a distinct phenomenon characterized by death of acinar cells and replacement by adipose tissue. Risk factors for developing NAFPD include obesity, increasing age, male sex, hypertension, dyslipidemia, alcohol and hyperferritinemia. Increasing evidence support the role of pancreatic fat in the development of type 2 diabetes mellitus, MetS, atherosclerosis, severe acute pancreatitis and even pancreatic cancer. Evidence exists that fatty pancreas could be used as the initial indicator of “ectopic fat deposition”, which is a key element of nonalcoholic fatty liver disease and/or MetS. Moreover, in patients with fatty pancreas, pancreaticoduodenectomy is associated with an increased risk of intraoperative blood loss and post-operative pancreatic fistula. PMID:27678349

  8. Olive oil consumption and non-alcoholic fatty liver disease.

    PubMed

    Assy, Nimer; Nassar, Faris; Nasser, Gattas; Grosovski, Maria

    2009-04-21

    The clinical implications of non-alcoholic fatty liver diseases (NAFLD) derive from their potential to progress to fibrosis and cirrhosis. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride (TG) accumulation. An olive oil-rich diet decreases accumulation of TGs in the liver, improves postprandial TGs, glucose and glucagon-like peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver. The principal mechanisms include: decreased nuclear factor-kappaB activation, decreased low-density lipoprotein oxidation, and improved insulin resistance by reduced production of inflammatory cytokines (tumor necrosis factor, interleukin-6) and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1. The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids, mainly from olive oil. In this review, we describe the dietary sources of the monounsaturated fatty acids, the composition of olive oil, dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis, clinical and experimental studies that assess the relationship between olive oil and NAFLD, and the mechanism by which olive oil ameliorates fatty liver, and we discuss future perspectives.

  9. Dietary approach in the treatment of nonalcoholic fatty liver disease

    PubMed Central

    Ferolla, Silvia Marinho; Silva, Luciana Costa; Ferrari, Maria de Lourdes Abreu; da Cunha, Aloísio Sales; Martins, Flaviano dos Santos; Couto, Cláudia Alves; Ferrari, Teresa Cristina Abreu

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) has been identified as one of the most prevalent chronic liver disease in adults and children populations. NAFLD is usually associated with the metabolic syndrome (MS), which is chiefly related to insulin resistance and its consequences. Insulin resistance has a crucial role in the pathogenesis of hepatic steatosis and potentially nonalcoholic steatohepatitis (NASH). Because of the contemporary epidemics of MS and obesity, the burden of NAFLD is also expected to rise. Unhealthy diets, such as the so-called western diet, are enriched in fructose, trans-fatty acids and saturated fat and seem to be associated with the development of NAFLD. In human studies, certain dietary sugars, particularly fructose, are used as a substrate for lipogenesis leading to hepatic fatty infiltration, inflammation, and possibly fibrosis. Other investigations have shown that fat consumption especially cholesterol and trans/saturated fatty acids are also steatogenic and seem to increase visceral adiposity. The identification of specific dietary components that favor the development of NASH could be important for the management of this disorder. This review focuses on the effects of different dietary approaches to prevent and treat NAFLD emphasizing the macronutrients and energy composition. PMID:26523205

  10. Epidemiology and risk factors of nonalcoholic fatty liver disease (NAFLD).

    PubMed

    Duseja, Ajay; Chalasani, Naga

    2013-12-01

    The nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic steatosis, determined by either imaging or histology, in the absence of secondary causes of hepatic fat accumulation. Nonalcoholic fatty liver is defined as the presence of hepatic steatosis with no evidence of hepatocellular injury in the form of ballooning of the hepatocytes or fibrosis. NASH is defined as the presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis. Although initial epidemiological studies have focused on its prevalence in the Western countries, it is becoming increasingly clear that NAFLD is highly prevalent in the Asia Pacific region, and there may be important distinctions in its phenotype between Asia Pacific and Western countries. Of particular interest are "lean NAFLD" and the "urban-rural divide," which will be discussed in this review article. Obesity, dyslipidemia, type 2 diabetes and metabolic syndrome are established risk factors for developing NAFLD. Many other risk factors (e.g., hypothyroidism, polycystic ovary syndrome, obstructive sleep apnea, hypopituitarism and hypogonadism) for NAFLD have been described in the Western countries, but these associations are yet to be investigated adequately in the Asia Pacific region.

  11. Translational approaches: from fatty liver to non-alcoholic steatohepatitis.

    PubMed

    Rosso, Natalia; Chavez-Tapia, Norberto C; Tiribelli, Claudio; Bellentani, Stefano

    2014-07-21

    Over the past few decades, non-alcoholic fatty liver disease (NAFLD) has become one, if not the most common, cause of chronic liver disease affecting both adults and children. The increasing number of cases at an early age is the most worrying aspect of this pathology, since it provides more time for its evolution. The spectrum of this disease ranges from liver steatosis to steatohepatitis, fibrosis and in some cases, hepatocellular carcinoma. NAFLD may not always be considered a benign disease and hepatologists must be cautious in the presence of fatty liver. This should prompt the use of the available experimental models to understand better the pathogenesis and to develop a rational treatment of a disease that is dangerously increasing. In spite of the growing efforts, the pathogenesis of NAFLD is still poorly understood. In the present article we review the most relevant hypotheses and evidence that account for the progression of NAFLD to non-alcoholic steatohepatitis (NASH) and fibrosis. The available in vitro and in vivo experimental models of NASH are discussed and revised in terms of their validity in translational studies. These studies must be aimed at the discovery of the still unknown triggers or mediators that induce the progression of hepatic inflammation, apoptosis and fibrosis.

  12. Paediatric non-alcoholic fatty liver disease: an overview.

    PubMed

    AlKhater, S A

    2015-05-01

    Non-alcoholic fatty liver disease (NAFLD) is a progressive disease that encompasses a spectrum of liver diseases, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Data related to survival in children are scarce, but these data firmly associate NAFLD with higher risks of hepatic and non-hepatic morbidities and mortalities compared with the general population. More recently, the association between NAFLD and cardiovascular disease among children has increasingly been recognized. Given that obesity is a major risk factor for the disease, paediatric NAFLD is becoming a global issue, paralleling the dramatic rise in obesity worldwide. NASH, which is more common in obese children, has the potential to advance to liver fibrosis and failure. It is unclear why certain patients undergo such transformation but this susceptibility is likely related to an interaction between a genetically susceptible host and the surrounding environment. Currently, treatment is largely conservative and includes lifestyle modification, attainable through healthy weight reduction via diet and exercise. In this review, current knowledge about NAFLD in children is summarized. This review aims to increase the awareness of the medical community about a hidden public health issue and to identify current gaps in the literature while providing directions for future research. © 2015 World Obesity.

  13. Non-alcoholic fatty liver disease: The diagnosis and management

    PubMed Central

    Abd El-Kader, Shehab M; El-Den Ashmawy, Eman M Salah

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is now the most frequent chronic liver disease that occurs across all age groups and is recognized to occur in 14%-30% of the general population, representing a serious and growing clinical problem due to the growing prevalence of obesity and overweight. Histologically, it resembles alcoholic liver injury but occurs in patients who deny significant alcohol consumption. NAFLD encompasses a spectrum of conditions, ranging from benign hepatocellular steatosis to inflammatory nonalcoholic steatohepatitis, fibrosis, and cirrhosis. The majority of hepatocellular lipids are stored as triglycerides, but other lipid metabolites, such as free fatty acids, cholesterol, and phospholipids, may also be present and play a role in disease progression. NAFLD is associated with obesity and insulin resistance and is considered the hepatic manifestation of the metabolic syndrome, a combination of medical conditions including type 2 diabetes mellitus, hypertension, hyperlipidemia, and visceral adiposity. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies; however, staging the disease requires a liver biopsy. Current treatment relies on weight loss and exercise, although various insulin-sensitizing agents, antioxidants and medications appear promising. The aim of this review is to highlight the current information regarding epidemiology, diagnosis, and management of NAFLD as well as new information about pathogenesis, diagnosis and management of this disease. PMID:25937862

  14. Pediatric nonalcoholic fatty liver disease: a multidisciplinary approach.

    PubMed

    Alisi, Anna; Feldstein, Ariel E; Villani, Alberto; Raponi, Massimiliano; Nobili, Valerio

    2012-01-17

    Nonalcoholic fatty liver disease (NAFLD) is a multifactorial condition, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) with or without fibrosis. NAFLD affects both adults and children who present with particular risk factors, including obesity, sedentary lifestyle and/or a predisposing genetic background. The escalation of the prevalence of NAFLD in children worldwide is a worrying phenomenon because this disease is closely associated with the development of both cirrhosis and cardiometabolic syndrome in adulthood. The etiopathogenesis of primary NAFLD in children is unknown; however, considerable knowledge about the mechanisms of liver damage that occur during disease progression has been gathered over the past 30 years. Understanding the pathogenetic mechanisms, together with the histological pattern, provide the basis to characterize potential early predictors of the disease, suitable noninvasive diagnostic tools and design novel specific treatments and possible management strategies. Despite a few clinical trials on the use of antioxidants combined with lifestyle intervention for NAFLD that showed encouraging results, to date, no treatment guidelines exist for children with NAFLD. In this Review, we provide an overview of current concepts in epidemiology, histological features, etiopathogenesis, diagnosis and treatment of NAFLD in children and adolescents.

  15. Nonalcoholic Steatohepatitis: A Search for Factual Animal Models

    PubMed Central

    Sanches, Sheila Cristina L.; Ramalho, Leandra Naira Z.; Augusto, Marlei Josiele; da Silva, Deisy Mara; Ramalho, Fernando Silva

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, which occurs in the absence of alcohol abuse. NAFLD can evolve into progressive liver injury and fibrosis in the form of nonalcoholic steatohepatitis (NASH). Several animal models have been developed to attempt to represent the morphological, biochemical, and clinical features of human NASH. The actual review presents a critical analysis of the most commonly used experimental models of NAFLD/NASH development. These models can be classified into genetic, nutritional, and a combination of genetic and nutritional factors. The main genetic models are ob/ob and db/db mutant mice and Zucker rats. The principal nutritional models employ methionine- and choline-deficient, high-fat, high-cholesterol and high-cholate, cafeteria, and high-fructose diets. Currently, associations between high-fructose and various compositions of high-fat diets have been widely studied. Previous studies have encountered significant difficulties in developing animal models capable of reproducing human NASH. Some models produce consistent morphological findings, but the induction method differs significantly compared with the pathophysiology of human NASH. Other models precisely represent the clinical and etiological contexts of this disease but fail to provide accurate histopathological representations mainly in the progression from steatosis to liver fibrosis. PMID:26064924

  16. Non-alcoholic fatty liver disease, diet and gut microbiota

    PubMed Central

    Finelli, Carmine; Tarantino, Giovanni

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a severe liver disease that is increasing in prevalence with the worldwide epidemic of obesity and its related insulin-resistance state. Evidence for the role of the gut microbiota in energy storage and the subsequent development of obesity and some of its related diseases is now well established. More recently, a new role of gut microbiota has emerged in NAFLD. The gut microbiota is involved in gut permeability, low-grade inflammation and immune balance, it modulates dietary choline metabolism, regulates bile acid metabolism and produces endogenous ethanol. All of these factors are molecular mechanisms by which the microbiota can induce NAFLD or its progression toward overt non-alcoholic steatohepatitis. Modification of the gut microbiota composition and/or its biochemical capacity by specific dietary or pharmacological interventions may advantageously affect host metabolism. Large-scale intervention trials, investigating the potential benefit of prebiotics and probiotics in improving cardiometabolic health in high-risk populations, are fervently awaited. PMID:26417275

  17. Noninvasive predictors for liver fibrosis in patients with nonalcoholic steatohepatitis

    PubMed Central

    Uslusoy, Hüseyin Saadettin; Nak, Selim Giray; Gülten, Macit

    2011-01-01

    AIM: To evaluate certain anthropometric, clinical and laboratory features indicating liver fibrosis in nonalcoholic steatohepatitis and to establish the noninvasive markers for liver fibrosis. METHODS: Eighty-one patients (40 male, 41 female) who were diagnosed with fatty liver by ultrasonographic examination and fulfilled the inclusion criteria participated in the study. Anamnesis, anthropometric, clinical and laboratory features of all cases were recorded and then liver biopsy was performed after obtaining patient consent. Steatosis, necroinflammation and liver fibrosis were examined according to age ≥ 45, gender, body mass index, central obesity, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 1, γ-glutamyltransferase (GGT)/ALT > 1, platelet count, insulin, c-peptide levels and the presence of hypertension, diabetes, hypertriglyceridemia and insulin resistance. RESULTS: Eighty-one patients with non-alcoholic steatohepatitis (NASH) enrolled in the study. 69 of 81 patients were diagnosed with NASH, 11 were diagnosed with simple fatty liver and 1 was diagnosed with cirrhosis. AST/ALT > 1, GGT/ALT > 11, high serum ferritin and fasting insulin levels, the presence of diabetes, hypertension, hypertriglyceridemia and insulin resistance seemed to enhance the severity of steatosis, necroinflammation and fibrosis but these results were not statistically significant. CONCLUSION: Liver steatosis and fibrosis can occur in individuals with normal weight. There was no significant concordance between severity of liver histology and the presence of predictors for liver fibrosis including metabolic risk factors. PMID:21954411

  18. Noninvasive predictors for liver fibrosis in patients with nonalcoholic steatohepatitis.

    PubMed

    Uslusoy, Hüseyin Saadettin; Nak, Selim Giray; Gülten, Macit

    2011-08-27

    To evaluate certain anthropometric, clinical and laboratory features indicating liver fibrosis in nonalcoholic steatohepatitis and to establish the noninvasive markers for liver fibrosis. Eighty-one patients (40 male, 41 female) who were diagnosed with fatty liver by ultrasonographic examination and fulfilled the inclusion criteria participated in the study. Anamnesis, anthropometric, clinical and laboratory features of all cases were recorded and then liver biopsy was performed after obtaining patient consent. Steatosis, necroinflammation and liver fibrosis were examined according to age ≥ 45, gender, body mass index, central obesity, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 1, γ-glutamyltransferase (GGT)/ALT > 1, platelet count, insulin, c-peptide levels and the presence of hypertension, diabetes, hypertriglyceridemia and insulin resistance. Eighty-one patients with non-alcoholic steatohepatitis (NASH) enrolled in the study. 69 of 81 patients were diagnosed with NASH, 11 were diagnosed with simple fatty liver and 1 was diagnosed with cirrhosis. AST/ALT > 1, GGT/ALT > 11, high serum ferritin and fasting insulin levels, the presence of diabetes, hypertension, hypertriglyceridemia and insulin resistance seemed to enhance the severity of steatosis, necroinflammation and fibrosis but these results were not statistically significant. Liver steatosis and fibrosis can occur in individuals with normal weight. There was no significant concordance between severity of liver histology and the presence of predictors for liver fibrosis including metabolic risk factors.

  19. Non-alcoholic steatohepatitis with normal aminotransferase values.

    PubMed

    Uslusoy, Hüseyin Saadettin; Nak, Selim Giray; Gülten, Macit; Biyikli, Zeynep

    2009-04-21

    To investigate the aspects of liver histology in patients with non-alcoholic steatohepatitis (NASH) who had normal aminotransferase levels. Thirty-four patients diagnosed with liver steatosis by ultrasonographic examination participated in the study. We compared all non-alcoholic fatty liver disease and NASH cases, according to aminotransferase level, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and presence of metabolic syndrome. Sixteen of 25 patients with high aminotransferase levels were diagnosed with NASH and nine with simple fatty liver according to liver histology. Among the nine patients with normal aminotransferase levels, seven had NASH and two had simple fatty liver. The patients with normal and high liver enzyme levels had almost the same prevalence of NASH and metabolic syndrome. Liver histology did not reveal any difference according to aminotransferase levels and AST/ALT ratio. Aminotransferase levels and AST/ALT ratio do not seem to be reliable predictors for NASH. Despite numerous non-invasive biomarkers, all patients with fatty liver should undergo liver biopsy.

  20. Non-alcoholic steatohepatitis with normal aminotransferase values

    PubMed Central

    Uslusoy, Hüseyin Saadettin; Nak, Selim Giray; Gülten, Macit; Bıyıklı, Zeynep

    2009-01-01

    AIM: To investigate the aspects of liver histology in patients with non-alcoholic steatohepatitis (NASH) who had normal aminotransferase levels. METHODS: Thirty-four patients diagnosed with liver steatosis by ultrasonographic examination participated in the study. We compared all non-alcoholic fatty liver disease and NASH cases, according to aminotransferase level, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and presence of metabolic syndrome. RESULTS: Sixteen of 25 patients with high aminotransferase levels were diagnosed with NASH and nine with simple fatty liver according to liver histology. Among the nine patients with normal aminotransferase levels, seven had NASH and two had simple fatty liver. The patients with normal and high liver enzyme levels had almost the same prevalence of NASH and metabolic syndrome. Liver histology did not reveal any difference according to aminotransferase levels and AST/ALT ratio. CONCLUSION: Aminotransferase levels and AST/ALT ratio do not seem to be reliable predictors for NASH. Despite numerous non-invasive biomarkers, all patients with fatty liver should undergo liver biopsy. PMID:19370784

  1. Current concepts and management approaches in nonalcoholic fatty liver disease.

    PubMed

    Attar, Bashar M; Van Thiel, David H

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver dysfunction worldwide. NAFLD may progress to nonalcoholic steatohepatitis (NASH) and in turn cirrhosis. Importantly, hepatic cancer can occur in NASH in the absence of cirrhosis. The cardinal histologic feature of NAFLD is the presence of an excessive accumulation of triacylglycerols and diacylglycerols in hepatocytes. The presence of obesity and insulin resistance lead to an increased hepatic-free fatty acid (FFA) flux creating an environment appropriate for the development of NAFLD. The generation of toxic reactive oxygen species with the production of hepatic injury and inflammation as a consequence of FFA oxidation will ultimately lead to the initiation and progression of fibrosis. Lifestyle modifications specifically weight loss, physical exercise, and cognitive behavior therapy have been recommended as treatments for NASH. Dietary fructose is an independent risk factor for the development of NAFLD. Pioglitazone can be used to treat biopsy-proven NASH; however, its safety risks should be considered carefully. Greater consumption for coffee, independent of its caffeine component, has been associated with a significant reduced risk of advanced fibrosis in NASH. Additional data are needed before recommending bariatric surgery as an established option for the specific treatment of NASH.

  2. Hyperlipidemic chicken as a model of non-alcoholic steatohepatitis.

    PubMed

    Ayala, Ignacio; Castillo, Antonia Martín; Adánez, Gracia; Fernández-Rufete, Ana; Pérez, Bartolomé García; Castells, Maria T

    2009-01-01

    Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD), currently the most common cause of abnormal liver tests. Given the difficulty of studying all the factors involved in it in human populations, studies in animal models might provide crucial insights in the pathogenesis of steatohepatitis. Several physiological features predispose birds to fat deposition in the liver. The present study was conceived to explore the possibilities of the chicken fed a cholesterol and fat enriched diet as a model for steatohepatitis. We used two different diets: a standard growing mash (control group) and a standard growing mash enriched with 2% cholesterol and 20% palm oil (hyperlipidemic group). We investigated the effect of feeding a cholesterol and fat enriched diet, on plasma lipid levels, liver enzymes and hepatic histopathology. Semiquantitative and quantitative assessment by image analysis was performed to determine changes in lipid deposits and inflammatory infiltration. Statistically significant increases were observed in all plasma lipid parameters, liver macroscopic features, fat deposits and cell-ballooning of hepatocytes between control and hyperlipidemic animals. Significant differences were also observed in the inflammatory infiltration parameters (number of foci, density, area and maximal diameter). Results show that diet-induced hypercholesterolemia and hypertriglyceridemia are associated with severe impairment of liver histology (fat accumulation, inflammation and cell-ballooning), reproducing histological features of human NAFLD. This model, which is easy and reproducible, offers economic and technical advantages. Furthermore, the reversibility of the pathologic changes makes it suitable for drug intervention studies of steatohepatitis.

  3. Low Hepatic Tissue Copper in Pediatric Nonalcoholic Fatty Liver Disease.

    PubMed

    Mendoza, Michael; Caltharp, Shelley; Song, Ming; Collin, Lindsay; Konomi, Juna V; McClain, Craig J; Vos, Miriam B

    2017-07-01

    Animal models and studies in adults have demonstrated that copper restriction increases severity of liver injury in nonalcoholic fatty liver disease (NAFLD). This has not been studied in children. We aimed to determine if lower tissue copper is associated with increased NAFLD severity in children. This was a retrospective study of pediatric patients who had a liver biopsy including a hepatic copper quantitation. The primary outcome compared hepatic copper concentration in NAFLD versus non-NAFLD. Secondary outcomes compared hepatic copper levels against steatosis, fibrosis, lobular inflammation, balloon degeneration, and NAFLD activity score (NAS). The study analysis included 150 pediatric subjects (102 with NAFLD and 48 non-NAFLD). After adjusting for age, body mass index z score, gamma glutamyl transferase, alanine aminotransferase, and total bilirubin, NAFLD subjects had lower levels of hepatic copper than non-NAFLD (P = 0.005). In addition, tissue copper concentration decreased as steatosis severity increased (P < 0.001). Copper levels were not associated with degree of fibrosis, lobular inflammation, portal inflammation, or balloon degeneration. In this cohort of pediatric subjects with NAFLD, we observed decreased tissue copper levels in subjects with NAFLD when compared with non-NAFLD subjects. In addition, tissue copper levels were lower in subjects with nonalcoholic steatohepatitis, a more severe form of the disease, when compared with steatosis alone. Further studies are needed to explore the relationship between copper levels and NAFLD progression.

  4. Questionnaire survey on lifestyle of patients with nonalcoholic steatohepatitis

    PubMed Central

    Noto, Haruka; Tokushige, Katsutoshi; Hashimoto, Etsuko; Taniai, Makiko; Shiratori, Keiko

    2014-01-01

    Lack of exercise and excessive food intake are known to be the important causes of nonalcoholic steatohepatitis (NASH). To elucidate the relationship between lifestyle and NASH, we surveyed exercise and dietary habits, comparing them among 171 biopsy-proven NASH patients, 29 nonalcoholic fatty liver (NAFL) patients and 49 normal subjects. Dietary habits including the duration of dinner time, amount of rice at dinner, and weekly frequencies of meat, fries, Chinese noodles, sweets, and instant food consumption were significantly different in male NASH patients compared to normal male subjects. In women, differences were seen in the amount of rice at dinner, frequency of eating out, and proclivity for sweets. In male NASH patients, the frequency of physical exercise was significantly lower. The lifestyle tendencies of NASH were almost similar to those of NAFL. In the comparison between obese NASH and non-obese NASH, no clear lifestyle differences were found. In conclusion, the most striking result of this survey was that the lifestyle of males contributed significantly to the development of NASH. These results point to treatment of NASH in males. In female NASH patients, lifestyle differences were minimal, and the effects of other factors such as genetic background will need to be investigated. PMID:25411525

  5. Non-alcoholic fatty liver disease and childhood obesity.

    PubMed

    Mathur, Prashant; Das, Manoja K; Arora, Narendra K

    2007-04-01

    Obesity has emerged as a significant global health problem in the pediatric population. Pediatric liver disease is a serious complication of childhood obesity. Non-alcoholic steatohepatitis (NASH) is an entity in the spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from fat in the liver--simple steatosis, NASH/ steatohepatitis--fat with in.ammation and/or fibrosis to advanced fibrosis and cirrhosis when fat may no longer be present. NASH is associated with obesity, diabetes, insulin resistance (IR), and hypertriglyceridemia. Children get NAFLD, and the incidence of this pediatric liver disease is rising as childhood obesity becomes increasingly prevalent. Although much remains to be learned about pediatric NAFLD, it is already evident that children with NASH risk progressive liver damage, including cirrhosis. Liver biopsy is required for definitive diagnosis, and other causes of fatty liver in childhood must be excluded. Gradual weight loss through increased regular exercise and a low-fat, low-refined carbohydrate diet appears to be effective. Drug treatments are being developed. The important message is that childhood obesity poses important health problems, including but not limited to potentially severe chronic liver disease. Early diagnosis of children who are only overweight is a worthy goal so that strategies to limit obesity can be instituted as early as possible. Identification of genetic risks is important, but management will invariably require changes in environmental factors. In addition to individual treatment, a multifaceted, societal initiative is required for solving the childhood obesity epidemic.

  6. Questionnaire survey on lifestyle of patients with nonalcoholic steatohepatitis.

    PubMed

    Noto, Haruka; Tokushige, Katsutoshi; Hashimoto, Etsuko; Taniai, Makiko; Shiratori, Keiko

    2014-11-01

    Lack of exercise and excessive food intake are known to be the important causes of nonalcoholic steatohepatitis (NASH). To elucidate the relationship between lifestyle and NASH, we surveyed exercise and dietary habits, comparing them among 171 biopsy-proven NASH patients, 29 nonalcoholic fatty liver (NAFL) patients and 49 normal subjects. Dietary habits including the duration of dinner time, amount of rice at dinner, and weekly frequencies of meat, fries, Chinese noodles, sweets, and instant food consumption were significantly different in male NASH patients compared to normal male subjects. In women, differences were seen in the amount of rice at dinner, frequency of eating out, and proclivity for sweets. In male NASH patients, the frequency of physical exercise was significantly lower. The lifestyle tendencies of NASH were almost similar to those of NAFL. In the comparison between obese NASH and non-obese NASH, no clear lifestyle differences were found. In conclusion, the most striking result of this survey was that the lifestyle of males contributed significantly to the development of NASH. These results point to treatment of NASH in males. In female NASH patients, lifestyle differences were minimal, and the effects of other factors such as genetic background will need to be investigated.

  7. Exploring the metabolic syndrome: Nonalcoholic fatty pancreas disease.

    PubMed

    Catanzaro, Roberto; Cuffari, Biagio; Italia, Angelo; Marotta, Francesco

    2016-09-14

    After the first description of fatty pancreas in 1933, the effects of pancreatic steatosis have been poorly investigated, compared with that of the liver. However, the interest of research is increasing. Fat accumulation, associated with obesity and the metabolic syndrome (MetS), has been defined as "fatty infiltration" or "nonalcoholic fatty pancreas disease" (NAFPD). The term "fatty replacement" describes a distinct phenomenon characterized by death of acinar cells and replacement by adipose tissue. Risk factors for developing NAFPD include obesity, increasing age, male sex, hypertension, dyslipidemia, alcohol and hyperferritinemia. Increasing evidence support the role of pancreatic fat in the development of type 2 diabetes mellitus, MetS, atherosclerosis, severe acute pancreatitis and even pancreatic cancer. Evidence exists that fatty pancreas could be used as the initial indicator of "ectopic fat deposition", which is a key element of nonalcoholic fatty liver disease and/or MetS. Moreover, in patients with fatty pancreas, pancreaticoduodenectomy is associated with an increased risk of intraoperative blood loss and post-operative pancreatic fistula.

  8. Non-alcoholic Fatty Liver Disease (NAFLD)--A Review.

    PubMed

    Karim, M F; Al-Mahtab, M; Rahman, S; Debnath, C R

    2015-10-01

    Non-alcoholic fatty liver disease (NAFLD) is an emerging problem in Hepatology clinics. It is closely related to the increased frequency of overweight or obesity. It has recognised association with metabolic syndrome. Central obesity, diabetes mellitus, dyslipidemia are commonest risk factors. Association with hepatitis C genotype 3 is also recognised. NAFLD is an important cause of cyptogenic cirrhosis of liver. It affects all populations and all age groups. Most patients with NAFLD are asymptomatic or vague upper abdominal pain. Liver function tests are mostly normal or mild elevation of aminotranferases. Histological features almost identical to those of alcohol-induced liver damage and can range from mild steatosis to cirrhosis. Two hit hypothesis is prevailing theory for the development of NAFLD. Diagnosis is usually made by imaging tools like ultrasonogram which reveal a bright liver while liver biopsy is gold standard for diagnosis as well as differentiating simple fatty liver and non-alcoholic steatohepatitis (NASH). Prognosis is variable. Simple hepatic steatosis generally has a benign long-term prognosis. However, one to two third of NASH progress to fibrosis or cirrhosis and may have a similar prognosis as cirrhosis from other liver diseases. Treatment is mostly control of underlying disorders and dietary advice, exercise, insulin sensitizers, antioxidants, or cytoprotective agents. The prevalence of NAFLD is increasing. So it needs more research to address this problem.

  9. Clinical approaches to non-alcoholic fatty liver disease

    PubMed Central

    Schwenger, Katherine JP; Allard, Johane P

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), leading to fibrosis and potentially cirrhosis, and it is one of the most common causes of liver disease worldwide. NAFLD is associated with other medical conditions such as metabolic syndrome, obesity, cardiovascular disease and diabetes. NASH can only be diagnosed through liver biopsy, but noninvasive techniques have been developed to identify patients who are most likely to have NASH or fibrosis, reducing the need for liver biopsy and risk to patients. Disease progression varies between individuals and is linked to a number of risk factors. Mechanisms involved in the pathogenesis are associated with diet and lifestyle, influx of free fatty acids to the liver from adipose tissue due to insulin resistance, hepatic oxidative stress, cytokines production, reduced very low-density lipoprotein secretion and intestinal microbiome. Weight loss through improved diet and increased physical activity has been the cornerstone therapy of NAFLD. Recent therapies such as pioglitazone and vitamin E have been shown to be beneficial. Omega 3 polyunsaturated fatty acids and statins may offer additional benefits. Bariatric surgery should be considered in morbidly obese patients. More research is needed to assess the impact of these treatments on a long-term basis. The objective of this article is to briefly review the diagnosis, management and treatment of this disease in order to aid clinicians in managing these patients. PMID:24587650

  10. Bile acid receptors and nonalcoholic fatty liver disease

    PubMed Central

    Yuan, Liyun; Bambha, Kiran

    2015-01-01

    With the high prevalence of obesity, diabetes, and other features of the metabolic syndrome in United States, nonalcoholic fatty liver disease (NAFLD) has inevitably become a very prevalent chronic liver disease and is now emerging as one of the leading indications for liver transplantation. Insulin resistance and derangement of lipid metabolism, accompanied by activation of the pro-inflammatory response and fibrogenesis, are essential pathways in the development of the more clinically significant form of NAFLD, known as nonalcoholic steatohepatitis (NASH). Recent advances in the functional characterization of bile acid receptors, such as farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor (TGR) 5, have provided further insight in the pathophysiology of NASH and have led to the development of potential therapeutic targets for NAFLD and NASH. Beyond maintaining bile acid metabolism, FXR and TGR5 also regulate lipid metabolism, maintain glucose homeostasis, increase energy expenditure, and ameliorate hepatic inflammation. These intriguing features have been exploited to develop bile acid analogues to target pathways in NAFLD and NASH pathogenesis. This review provides a brief overview of the pathogenesis of NAFLD and NASH, and then delves into the biological functions of bile acid receptors, particularly with respect to NASH pathogenesis, with a description of the associated experimental data, and, finally, we discuss the prospects of bile acid analogues in the treatment of NAFLD and NASH. PMID:26668692

  11. Epigenetics in non-alcoholic fatty liver disease.

    PubMed

    Lee, Jooho; Kim, Yuri; Friso, Simonetta; Choi, Sang-Woon

    2017-04-01

    Non-alcoholic fatty liver disease (NAFLD), a common hepatic disorder ranging from simple steatosis through steatohepatitis to fibrosis and cirrhosis, is an emerging health concern. NAFLD is a pathologic condition characterized by the buildup of extra fat in liver cells that is not caused by alcohol consumption. Excess hepatic fat accumulation results from increased delivery of triglycerides (TG) to the liver or conversion of surplus carbohydrates to TG. Importantly, a subgroup of NAFLD results in hepatocellular injury and inflammation, which is referred to as non-alcoholic steatohepatitis (NASH), and may progress to irreversible cirrhosis and hepatocellular carcinoma (HCC). NAFLD shares, in part, the common pathogenesis of metabolic syndrome including obesity, hyperlipidemia, insulin resistance, mitochondrial damage, oxidative stress response, and the release of inflammatory cytokines. Epigenetics, an inheritable phenomenon that affects gene expression without altering the DNA sequence, provides a new perspective on the pathogenesis of NAFLD. Reversible epigenetic changes take place at the transcriptional level and provide a phenotypic connection between the host and environment. An accumulating body of evidence suggests the importance of epigenetic roles in NAFLD, which in turn can be identified as potential therapeutic targets and non-invasive biomarkers of NAFLD. It is anticipated that the epigenetic modifiers in NAFLD may provide novel molecular indicators that can determine not only the initial risk but also the disease progression and prognosis. In the present review, we update the roles of epigenetics as pathologic mechanisms, therapeutic targets and biomarkers in NAFLD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Role of liver biopsy in nonalcoholic fatty liver disease

    PubMed Central

    Nalbantoglu, ILKe; Brunt, Elizabeth M

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (> 5%) of hepatic triglyceride without excess alcohol intake, is the most common form of chronic liver disease in adults and children in the United States. NAFLD encompasses a spectrum of histologic findings including uncomplicated steatosis, steatosis with inflammation and steatohepatitis [nonalcoholic steatohepatitis (NASH)]; the latter can advance to cirrhosis and hepatocellular carcinoma. NASH is currently accepted as the hepatic manifestation of the set of cardiovascular risk factors collectively known as metabolic syndrome. In 1999 a system for histologic grading and staging for NASH was proposed; this was revised by the NASH Clinical Research Network in 2005 for the entire spectrum of lesions in NAFLD, including the lesions and patterns of pediatric NAFLD, and for application in clinical research trials. Diagnosis remains distinct from grade and stage. A recent European proposal separates steatosis from activity to derive a numeric diagnosis of NASH. Even though there have been promising advancements in non-invasive testing, these tests are not yet detailed enough to replace the full range of findings provided by liver biopsy evaluation. Limitations of biopsy are acknowledged, but liver biopsy remains the “gold standard” for diagnosis and determination of amounts of necroinflammatory activity, and location of fibrosis, as well as remodeling of the parenchyma in NASH. This review focuses on the specific histologic lesions of NAFLD and NASH, grading and staging, differential diagnoses to be considered, and the continuing role of the liver biopsy in this important liver disease. PMID:25083076

  13. Autophagy and non-alcoholic fatty liver disease.

    PubMed

    Lavallard, Vanessa J; Gual, Philippe

    2014-01-01

    Autophagy, or cellular self-digestion, is a catabolic process that targets cell constituents including damaged organelles, unfolded proteins, and intracellular pathogens to lysosomes for degradation. Autophagy is crucial for development, differentiation, survival, and homeostasis. Important links between the regulation of autophagy and liver complications associated with obesity, non-alcoholic fatty liver disease (NAFLD), have been reported. The spectrum of these hepatic abnormalities extends from isolated steatosis to non-alcoholic steatohepatitis (NASH), steatofibrosis, which sometimes leads to cirrhosis, and hepatocellular carcinoma. NAFLD is one of the three main causes of cirrhosis and increases the risk of liver-related death and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of a normal liver to steatosis and then more severe disease are complex and still unclear. The regulation of the autophagic flux, a dynamic response, and the knowledge of the role of autophagy in specific cells including hepatocytes, hepatic stellate cells, immune cells, and hepatic cancer cells have been extensively studied these last years. This review will provide insight into the current understanding of autophagy and its role in the evolution of the hepatic complications associated with obesity, from steatosis to hepatocellular carcinoma.

  14. Multidisciplinary Pharmacotherapeutic Options for Nonalcoholic Fatty Liver Disease

    PubMed Central

    Nakajima, Kei

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are multidisciplinary liver diseases that often accompany type 2 diabetes or metabolic syndrome, which are characterized by insulin resistance. Therefore, effective treatment of type 2 diabetes and metabolic syndrome should target not only the cardiometabolic abnormalities, but also the associated liver disorders. In the last decade, it has been shown that metformin, thiazolidinediones, vitamin E, ezetimibe, n-3 polyunsaturated fatty acids, renin-angiotensin system (RAS) blockers, and antiobesity drugs may improve hepatic pathophysiological disorders as well as clinical parameters. Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1) inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. However, the efficacy, safety, and tolerability of long-term treatment (potentially for many years) with these drugs have not been fully established. Furthermore, clinical trials have not comprehensively examined the efficacy of lipid-lowering drugs (i.e., statins, fibrates, and NPC1L1 inhibitors) for the treatment of NAFLD. Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors) is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain. PMID:23304532

  15. Dietary habits and behaviors associated with nonalcoholic fatty liver disease

    PubMed Central

    Yasutake, Kenichiro; Kohjima, Motoyuki; Kotoh, Kazuhiro; Nakashima, Manabu; Nakamuta, Makoto; Enjoji, Munechika

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent causes of health problems in Western (industrialized) countries. Moreover, the incidence of infantile NAFLD is increasing, with some of these patients progressing to nonalcoholic steatohepatitis. These trends depend on dietary habits and life-style. In particular, overeating and its associated obesity affect the development of NAFLD. Nutritional problems in patients with NAFLD include excess intake of energy, carbohydrates, and lipids, and shortages of polyunsaturated fatty acids, vitamins, and minerals. Although nutritional therapeutic approaches are required for prophylaxis and treatment of NAFLD, continuous nutrition therapy is difficult for many patients because of their dietary habits and lifestyle, and because the motivation for treatment differs among patients. Thus, it is necessary to assess the nutritional background and to identify nutritional problems in each patient with NAFLD. When assessing dietary habits, it is important to individually evaluate those that are consumed excessively or insufficiently, as well as inappropriate eating behaviors. Successful nutrition therapy requires patient education, based on assessments of individual nutrients, and continuing the treatment. In this article, we update knowledge about NAFLD, review the important aspects of nutritional assessment targeting treatment success, and present some concrete nutritional care plans which can be applied generally. PMID:24587653

  16. Autophagy and Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Lavallard, Vanessa J.

    2014-01-01

    Autophagy, or cellular self-digestion, is a catabolic process that targets cell constituents including damaged organelles, unfolded proteins, and intracellular pathogens to lysosomes for degradation. Autophagy is crucial for development, differentiation, survival, and homeostasis. Important links between the regulation of autophagy and liver complications associated with obesity, non-alcoholic fatty liver disease (NAFLD), have been reported. The spectrum of these hepatic abnormalities extends from isolated steatosis to non-alcoholic steatohepatitis (NASH), steatofibrosis, which sometimes leads to cirrhosis, and hepatocellular carcinoma. NAFLD is one of the three main causes of cirrhosis and increases the risk of liver-related death and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of a normal liver to steatosis and then more severe disease are complex and still unclear. The regulation of the autophagic flux, a dynamic response, and the knowledge of the role of autophagy in specific cells including hepatocytes, hepatic stellate cells, immune cells, and hepatic cancer cells have been extensively studied these last years. This review will provide insight into the current understanding of autophagy and its role in the evolution of the hepatic complications associated with obesity, from steatosis to hepatocellular carcinoma. PMID:25295245

  17. Translational approaches: From fatty liver to non-alcoholic steatohepatitis

    PubMed Central

    Rosso, Natalia; Chavez-Tapia, Norberto C; Tiribelli, Claudio; Bellentani, Stefano

    2014-01-01

    Over the past few decades, non-alcoholic fatty liver disease (NAFLD) has become one, if not the most common, cause of chronic liver disease affecting both adults and children. The increasing number of cases at an early age is the most worrying aspect of this pathology, since it provides more time for its evolution. The spectrum of this disease ranges from liver steatosis to steatohepatitis, fibrosis and in some cases, hepatocellular carcinoma. NAFLD may not always be considered a benign disease and hepatologists must be cautious in the presence of fatty liver. This should prompt the use of the available experimental models to understand better the pathogenesis and to develop a rational treatment of a disease that is dangerously increasing. In spite of the growing efforts, the pathogenesis of NAFLD is still poorly understood. In the present article we review the most relevant hypotheses and evidence that account for the progression of NAFLD to non-alcoholic steatohepatitis (NASH) and fibrosis. The available in vitro and in vivo experimental models of NASH are discussed and revised in terms of their validity in translational studies. These studies must be aimed at the discovery of the still unknown triggers or mediators that induce the progression of hepatic inflammation, apoptosis and fibrosis. PMID:25083077

  18. Nonalcoholic fatty liver disease in chronic obstructive pulmonary disease.

    PubMed

    Viglino, Damien; Jullian-Desayes, Ingrid; Minoves, Mélanie; Aron-Wisnewsky, Judith; Leroy, Vincent; Zarski, Jean-Pierre; Tamisier, Renaud; Joyeux-Faure, Marie; Pépin, Jean-Louis

    2017-06-01

    Nonalcoholic fatty liver disease (NAFLD) is independently linked to cardiometabolic morbidity and mortality. Low-grade inflammation, oxidative stress and ectopic fat, common features of chronic obstructive pulmonary disease (COPD), might contribute to the development of NAFLD.We aimed to investigate the prevalence of NAFLD and to evaluate the relationship between various types of liver damage and COPD severity, comorbidities and circulating inflammatory cytokines. Validated noninvasive tests (FibroMax: SteatoTest, NashTest and FibroTest) were used to assess steatosis, nonalcoholic steatohepatitis (NASH) and liver fibrosis. Patients underwent an objective assessment of COPD comorbidities, including sleep studies. Biological parameters included a complete lipid profile and inflammatory markers.In COPD patients the prevalence of steatosis, NASH and fibrosis were 41.4%, 36.9% and 61.3%, respectively. In multivariate analysis, SteatoTest and FibroTest were significantly associated with sex, body mass index (BMI), untreated sleep apnoea and insulin resistance, and, in addition, COPD Global Initiative for Chronic Obstructive Lung Disease stage for SteatoTest. Patients with steatosis had higher tumour necrosis factor-α levels and those with NASH or a combination of liver damage types had raised leptin levels after adjustment for age, sex and BMI.We concluded that NAFLD is highly prevalent in COPD and might contribute to cardiometabolic comorbidities. Copyright ©ERS 2017.

  19. Nonalcoholic fatty liver disease and aging: Epidemiology to management

    PubMed Central

    Bertolotti, Marco; Lonardo, Amedeo; Mussi, Chiara; Baldelli, Enrica; Pellegrini, Elisa; Ballestri, Stefano; Romagnoli, Dante; Loria, Paola

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is common in the elderly, in whom it carries a more substantial burden of hepatic (nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma) and extra-hepatic manifestations and complications (cardiovascular disease, extrahepatic neoplasms) than in younger age groups. Therefore, proper identification and management of this condition is a major task for clinical geriatricians and geriatric hepatologists. In this paper, the epidemiology and pathophysiology of this condition are reviewed, and a full discussion of the link between NAFLD and the aspects that are peculiar to elderly individuals is provided; these aspects include frailty, multimorbidity, polypharmacy and dementia. The proper treatment strategy will have to consider the peculiarities of geriatric patients, so a multidisciplinary approach is mandatory. Non-pharmacological treatment (diet and physical exercise) has to be tailored individually considering the physical limitations of most elderly people and the need for an adequate caloric supply. Similarly, the choice of drug treatment must carefully balance the benefits and risks in terms of adverse events and pharmacological interactions in the common context of both multiple health conditions and polypharmacy. In conclusion, further epidemiological and pathophysiological insight is warranted. More accurate understanding of the molecular mechanisms of geriatric NAFLD will help in identifying the most appropriate diagnostic and therapeutic approach for individual elderly patients. PMID:25339806

  20. Nonalcoholic steatohepatitis: emerging targeted therapies to optimize treatment options

    PubMed Central

    Milic, Sandra; Mikolasevic, Ivana; Krznaric-Zrnic, Irena; Stanic, Marija; Poropat, Goran; Stimac, Davor; Vlahovic-Palcevski, Vera; Orlic, Lidija

    2015-01-01

    Diet and lifestyle changes have led to worldwide increases in the prevalences of obesity and metabolic syndrome, resulting in substantially greater incidence of nonalcoholic fatty liver disease (NAFLD). NAFLD is considered a hepatic manifestation of metabolic syndrome and is related to diabetes, insulin resistance, central obesity, hyperlipidemia, and hypertension. Nonalcoholic steatohepatitis (NASH) is an entity that describes liver inflammation due to NAFLD. Growing evidence suggests that NAFLD is a multisystem disease with a clinical burden that is not only confined to liver-related morbidity and mortality, but that also affects several extra-hepatic organs and regulatory pathways. Thus, NAFLD is considered an important public health issue, but there is currently no effective therapy for all NAFLD patients in the general population. Studies seeking optimal therapy for NAFLD and NASH have not yet led to development of a universal protocol for treating this growing problem. Several pharmacological agents have been studied in an effort to improve insulin resistance and the proinflammatory mediators that may be responsible for NASH progression. Cardiovascular risk factors are highly prevalent among NASH patients, and the backbone of treatment regimens for these patients still comprises general lifestyle interventions, including dietary changes and increased physical activity. Vitamin E and thiazolidinedione derivatives are currently the most evidence-based therapeutic options, but only limited clinical evidence is available regarding their long-term efficacy and safety. Vitamin D and renin–angiotensin–aldosterone system blockers are promising drugs that are currently being intensively investigated for use in NAFLD/NASH patients. PMID:26316717

  1. Interaction of type 2 diabetes and nonalcoholic fatty liver disease.

    PubMed

    Verderese, John Paul; Younossi, Zobair

    2013-07-01

    Evauation of: Kasturiratne A, Weerasinghe S, Dassanayake A et al. Influence of non-alcoholic fatty liver disease on the development of diabetes mellitus. J. Gastroenterol. Hepatol. 28(1), 142-147 (2013). It has been a few decades that Type 2 diabetes has been clearly linked to the development and progression of nonalcoholic fatty liver disease (NAFLD). In a recent study reported by Kastuiratne et al., the reverse scenario is also reported. In this study, a cohort of Sri Lankan adults were evaluated for NAFLD by ultrasound and for the presence of Type 2 diabetes. Those without diabetes at baseline were followed prospectively for 3 years and assessed for incident diabetes. On multivariate analysis, after adjustment for a number of factors (age, impaired fasting glucose, BMI, waist circumference, elevated ALT, family history of diabetes and presence of hypertension and hyperlipidemia), NAFLD was the only predictor of incident diabetes in those with and without impaired fasting glucose at baseline. This study adds to the growing evidence connecting NAFLD to Type 2 diabetes and highlights the importance of its recognition in an effort to target those at the highest risk of diabetes for lifestyle and pharmacologic intervention.

  2. Non-alcoholic fatty liver disease in 2015

    PubMed Central

    Ahmed, Monjur

    2015-01-01

    There is worldwide epidemic of non-alcoholic fatty liver disease (NAFLD). NAFLD is a clinical entity related to metabolic syndrome. Majority of the patients are obese but the disease can affect non-obese individuals as well. Metabolic factors and genetics play important roles in the pathogenesis of this disorder. The spectrum of disorders included in NAFLD are benign macrovesicular hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis of liver and hepatocellular carcinoma. Although the disease remains asymptomatic most of the time, it can slowly progress to end stage liver disease. It will be the most common indication of liver transplantation in the future. It is diagnosed by abnormal liver chemistry, imaging studies and liver biopsy. As there are risks of potential complications during liver biopsy, many patients do not opt for liver biopsy. There are some noninvasive scoring systems to find out whether patients have advanced hepatic fibrosis. At the present time, there are limited treatment options which include lifestyle modification to loose weight, vitamin E and thioglitazones. Different therapeutic agents are being investigated for optimal management of this entity. There are some studies done on incretin based therapies in patients with NAFLD. Other potential agents will be silent information regulator protein Sirtuin and antifibrotic monoclonal antibody Simtuzumab against lysyl oxidase like molecule 2. But they are still in the investigational phase. PMID:26085906

  3. Nonalcoholic fatty liver disease and cholesterol gallstones: which comes first?

    PubMed

    Ahmed, Mohamed H; Ali, Asif

    2014-05-01

    Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GD) are both highly prevalent in the general population and are associated with obesity, insulin resistance, dyslipidemia, and high dietary cholesterol intake. Insulin resistance is a key feature of both NAFLD and GD. Hepatic insulin resistance provides a crucial link between the metabolic syndrome, NAFLD, and increased cholesterol gallstone susceptibility. Hepatic insulin resistance is not only associated with accumulation of hepatic fat but also has a crucial role in supersaturation and excessive production of bile salts. It is not yet clear whether NAFLD is a precursor of GD or whether the presence of GD possibly indicates the presence of long-standing features of metabolic syndrome that accelerates the progression of NAFLD. Recent reports suggested the association between gallstones and nonalcoholic steatohepatitis and liver fibrosis. Importantly, both NAFLD and GD are both associated with high incidence of cardiovascular disease (CVD) and mortality. Emerging evidence suggests a potential benefit of statin therapy in NAFLD and GD. Further research is needed to determine (i) how the presence of NAFLD and GD is associated with CVD (ii) and whether the presence of GD in association with NAFLD increases the risk of liver fibrosis, and (iii) the impact of therapy of NAFLD in the incidence of GD.

  4. Drug metabolism alterations in nonalcoholic fatty liver disease

    PubMed Central

    Merrell, Matthew D.; Cherrington, Nathan J.

    2013-01-01

    Drug-metabolizing enzymes play a vital role in the elimination of the majority of therapeutic drugs. The major organ involved in drug metabolism is the liver. Chronic liver diseases have been identified as a potential source of significant interindividual variation in metabolism. Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States, affecting between 60 and 90 million Americans, yet the vast majority of NAFLD patients are undiagnosed. NAFLD encompasses a spectrum of pathologies, ranging from steatosis to nonalcoholic steatohepatitis and fibrosis. Numerous animal studies have investigated the effects of NAFLD on hepatic gene expression, observing significant alterations in mRNA, protein, and activity levels. Information on the effects of NAFLD in human patients is limited, though several significant investigations have recently been published. Significant alterations in the activity of drug-metabolizing enzymes may affect the clearance of therapeutic drugs, with the potential to result in adverse drug reactions. With the enormous prevalence of NAFLD, it is conceivable that every drug currently on the market is being given to patients with NAFLD. The current review is intended to present the results from both animal models and human patients, summarizing the observed alterations in the expression and activity of the phase I and II drug-metabolizing enzymes. PMID:21612324

  5. Molecular mechanisms of hepatic fibrosis in non-alcoholic steatohepatitis.

    PubMed

    Rombouts, Krista; Marra, Fabio

    2010-01-01

    Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in Western countries. The more severe form of this condition, non-alcoholic steatohepatitis (NASH), may progress to cirrhosis and its complications. Fibrosis and cirrhosis are the final outcomes of all chronic liver diseases; however, some morphological and biological differences distinguish fibrosis due to NASH from the forms secondary to other causes of liver damage. Fibrosis due to NASH develops primarily in the pericentral areas, surrounding groups of hepatocytes and thickening the space of Disse. This pericellular fibrosis eventually forms septa isolating regenerating nodules. The main cell type responsible for extracellular matrix deposition is represented by hepatic stellate cells that undergo activation in conditions of liver injury enabling them to participate in the liver wound healing process. Although the profibrogenic mechanisms operating in NASH are partly in common with those observed in other chronic liver diseases, the altered pattern of circulating adipokines, oxidative stress generation and the hormonal profile associated with the metabolic syndrome might have a specific role for the induction of fibrogenesis in this condition. In this paper, we review recent developments regarding the basic mechanisms of NASH and the involvement of hepatic stellate cells in this disease.

  6. The Effectiveness of Lactation Consultants and Lactation Counselors on Breastfeeding Outcomes.

    PubMed

    Patel, Sanjay; Patel, Shveta

    2016-08-01

    Breastfeeding for all infants starting at birth and continuing until at least 6 months of age has been recommended by the World Health Organization and the American Academy of Pediatrics. The health benefits to infants and mothers have been demonstrated in many studies. Dedicated lactation specialists may play a role in providing education and support to pregnant women and new mothers wishing to breastfeed to improve breastfeeding outcomes. The objective of this review was to assess if lactation education or support programs using lactation consultants or lactation counselors would improve rates of initiation and duration of any breastfeeding and exclusive breastfeeding compared with usual practice. A systematic literature review of the evidence was conducted using electronic databases. The review was limited to randomized trials and yielded 16 studies with 5084 participants. It was found that breastfeeding interventions using lactation consultants and counselors increase the number of women initiating breastfeeding (odds ratio [OR] for any initiation vs not initiating breastfeeding = 1.35; 95% confidence interval [CI], 1.10-1.67). The interventions improve any breastfeeding rates (OR for any breastfeeding up to 1 month vs not breastfeeding = 1.49; 95% CI, 1.09-2.04). In addition, there were beneficial effects on exclusive breastfeeding rates (OR for exclusive breastfeeding up to 1 month vs not exclusive breastfeeding = 1.71; 95% CI, 1.20-2.44). Most of the evidence would suggest developing and improving postpartum support programs incorporating lactation consultants and lactation counselors. © The Author(s) 2015.

  7. Diet for a Healthy Lactating Woman.

    PubMed

    Kolasa, Kathryn M; Firnhaber, Gina; Haven, Kelley

    2015-12-01

    The nutrient and caloric requirements for lactation are set by the Institute of Medicine. The dietary pattern to meet those needs is found in the Dietary Guidelines for Americans. Only deficiency states for selected nutrients and/or prolonged inadequate caloric intake appear to affect the volume and quality of breast milk. Other dietary concerns of lactating women include "dieting" to return to prepregnancy weight; low maternal intake of selected nutrients due to health conditions or food choices; need for supplementation of calcium, vitamin D, and fatty acids; and use of non-nutritive sweeteners, caffeine, herbal supplements, and alcohol.

  8. Breast diseases during pregnancy and lactation

    PubMed Central

    Yu, Ji Hoon; Kim, Min Jeong; Cho, Hyonil; Liu, Hyun Ju; Han, Sei-Jun

    2013-01-01

    Breast is a typical female sexual physiologic organ that is influenced by steroid hormone from menarche until menopause. Therefore various diseases can be developed by continuous action of estrogen and progesterone. Breast diseases are mainly categorized as benign and malignant. It is very important to distinguish the malignancy from breast diseases. However, it is very difficult to diagnose malignancy in pregnant and lactating women even though the same breast diseases took place. Therefore, we will review breast diseases such as breast carcinoma during pregnancy and lactation. PMID:24327995

  9. Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in Albanian overweight children.

    PubMed

    Kodhelaj, K; Resuli, B; Petrela, E; Malaj, V; Jaze, H

    2014-02-01

    Overweight and obesity has emerged as a significant global health problem in the pediatric population. Childhood non-alcoholic fatty liver disease (NAFLD) has become a common and important liver disease. Although mostly benign, some children with NAFLD develop fibrosis and in some case cirrhosis. The aims of this study were to determine the prevalence of NAFLD/non-alcoholic steatohepatitis (NASH) in overweight Albanian children, to evaluate the demographic and biochemical details and to assess the association between the severity of fatty liver changes and demographic and biochemical abnormalities. A total of 80 school aged children, 24 overweight (85th≤BMI≤94th percentile) and 55 obese (BMI≥94th percentile), aged 10.43±2.2 years (M±SD) were included in the current study, in January-December 2010. Their age was in the range of 7-15 years. Their sex distribution was 36 female and 44 male. The children were enrolled to the Tirana schools and none of them were part of any weight or diet programmer. Children who were found to have TBC, evidence of HBV or HCV, infections, drug toxicity, autoimmune hepatitis, inborn error of metabolism or concomitant cortisteroid therapy were excluded. Laboratory parameters were measured at the time of bioclinical examinations. Fatty liver was diagnosed by ultrasonography detection of the most characteristic features of fatty infiltration. The scoring system was used in order to graduate the severity of the disease. The child was considered to have mild, moderate and severe fatty liver changes if the overall score was 1-3, 4-6 and 7-9, respectively. Multivariate regression analysis was used to assess the association between the different variables and the severity of NAFLD. NAFLD was present in 55/80 (68.7%) of the overweight children, 34 (61.8%) boys and 21 (38.2%) girls. Mild, moderate and severe degree of fatty liver were found in 35 (43.7%), 19 (23.7%) and 1 (1.3%), respectively. Nash was seen in 13 (23.7%) of the children

  10. Lactate study using umbilical cord blood: agreement between Lactate Pro hand-held devices with blood gas analyser and evaluation of lactate stability over time.

    PubMed

    Su, Tina Y; Reece, Mifanwy; Chua, Seng C

    2013-08-01

    Lactate measurements have become increasingly preferred over pH analysis in the evaluation of fetal acidaemia in labour. In a busy labour ward, often the umbilical cord may be sampled late and as a result yield unreliable lactate values. To investigate the agreement of hand-held device Lactate Pro with a reference method blood gas analyser and evaluate the stability of umbilical cord lactate values over time. Prospective study carried out at elective caesarean section. Sixteen umbilical cords were double clamped immediately after delivery with paired arterial and venous blood samples collected by an independent researcher, at varying time intervals, and processed by two Lactate Pro devices and a reference method blood gas analyser. A significant difference of -0.41 to 0.10 mmol/L was found when different groups of Lactate Pro devices were compared with blood gas analyser at lactate values up to 5.70 mmol/L, with average lactate value of 2.45 mmol/L. Over time, there is progressive rise in lactate samples obtained from the umbilical cord. Lactate Pro devices have a significant difference, but when used in clinical practice on cord blood after delivery, this is unlikely to be meaningful. In intrapartum fetal surveillance, a systematic overestimation might lead to unnecessary intervention. It is possible to retrospectively predict the likely level of lactate at birth in delayed cord samples. © 2013 The Authors ANZJOG © 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  11. Effect of oleoylethanolamide on diet-induced nonalcoholic fatty liver in rats.

    PubMed

    Li, Long; Li, Lei; Chen, Ling; Lin, Xiaoyu; Xu, Yaping; Ren, Jie; Fu, Jin; Qiu, Yan

    2015-03-01

    Oleoylethanolamine (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor alpha (PPAR-α), has revealed the pharmacological properties in the treatment of obesity, atherosclerosis and other diseases through the modulation of lipid metabolism. To assess whether OEA can also regulate non-alcoholic fatty liver disease (NAFLD) caused by fat accumulation, we administrated OEA or fenofibrate in Sprague Dawley (SD) rats fed with a high fat diet (HFD). After 6 or 17 weeks treatment, OEA (5 mg/kg/day, i.p.) relieved the development of NAFLD compared with control groups by regulating the levels of plasma TG, TC, ALT and AST and liver inflammatory cytokines. Gene expression analysis of liver tissue and plasma from the animal models showed that OEA and fenofibrate both promoted the lipid β-oxidation by activating PPAR-α. Detailed research revealed that OEA inhibited the mRNA expression of lipogenesis in a PPAR-α-independant manner, while fenofibrate expressed an opposite effection. In summary, our research results suggested that as a potential lead compound, OEA could improve HFD-induced NAFLD with higher efficacy and safety than fenofibrate. Copyright © 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

  12. Beer and wine consumers' perceptions of the nutritional value of alcoholic and nonalcoholic beverages.

    PubMed

    Wright, C A; Bruhn, C M; Heymann, H; Bamforth, C W

    2008-01-01

    In general beer has not been portrayed as part of a balanced diet. However, red wine has been promoted as a beneficial part of a nutritious diet. The evidence is that beer is at least the equal of wine from a nutritional perspective and in countering ailments such as coronary heart disease. This study used surveys to compare beer and wine consumers' perceptions of alcoholic and nonalcoholic beverages. The consumers ranked 7 beverages based upon perceived healthfulness both before and after they were exposed to nutritional information about the beverages. The ranked data were analyzed using analysis of variance. The variance due to the 3-way interaction of place of recruitment, beverage, and ranking was found to be significant at P < 0.05. There was no significant difference between genders. Overall, consumers of alcoholic beverages perceived red wine to be more healthful than the other 6 beverages, including beer and white wine. The perceived healthfulness of a beverage does not appear to be the main factor driving the choice of beverage. Nutritional information does impact consumers' perceptions of the healthfulness of beverages. Consumers who are predominately beer drinkers were more heavily influenced by nutritional information than consumers who were predominately wine drinkers.

  13. Insulin resistance in development and progression of nonalcoholic fatty liver disease

    PubMed Central

    Alam, Shahinul; Mustafa, Golam; Alam, Mahabubul; Ahmad, Nooruddin

    2016-01-01

    Although insulin resistance (IR) is strongly associated with nonalcoholic fatty liver disease (NAFLD), the association of IR and NAFLD is not universal and correlation between IR and severity of NAFLD is still controversial. In this review, we summarize recent evidence that partially dissociates insulin resistance from NAFLD. It has also been reported that single-nucleotide polymorphisms in the diacylglycerol acyltransferase gene, rather than IR, account for the variability in liver fat content. Polymorphisms of the patatin-like phospholipase 3 gene have also been reported to be associated with NAFLD without metabolic syndrome, which suggests that genetic conditions that promote the development of fatty changes in the liver may occur independently of IR. Moreover, environmental factors such as nutrition and physical activity as well as small intestinal bacterial overgrowth have been linked to the pathogenesis of NAFLD, although some of the data are conflicting. Therefore, findings from both genetically engineered animal models and humans with genetic conditions, as well as recent studies that have explored the role of environmental factors, have confirmed the view that NAFLD is a polygenic disease process caused by both genetic and environmental factors. Therefore, IR is not the sole predictor of the pathogenesis of NAFLD. PMID:27190693

  14. Gut-liver axis and probiotics: their role in non-alcoholic fatty liver disease.

    PubMed

    Paolella, Giulia; Mandato, Claudia; Pierri, Luca; Poeta, Marco; Di Stasi, Martina; Vajro, Pietro

    2014-11-14

    The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a "low bacterial richness" may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier ("leaky gut"), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.

  15. Gut-liver axis and probiotics: Their role in non-alcoholic fatty liver disease

    PubMed Central

    Paolella, Giulia; Mandato, Claudia; Pierri, Luca; Poeta, Marco; Di Stasi, Martina; Vajro, Pietro

    2014-01-01

    The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a “low bacterial richness” may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (“leaky gut”), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy. PMID:25400436

  16. Nonalcoholic steatohepatitis-related hepatocellular carcinoma: is there a role for the androgen receptor pathway?

    PubMed Central

    Ali, Mahmoud A; Lacin, Sahin; Abdel-Wahab, Reham; Uemura, Mark; Hassan, Manal; Rashid, Asif; Duda, Dan G; Kaseb, Ahmed O

    2017-01-01

    The epidemic of insulin resistance, obesity, and metabolic syndrome has led to the emergence of nonalcoholic steatohepatitis (NASH) as the most common cause of liver disease in the US. Patients with NASH are at an increased risk for hepatic disease-related morbidity and death, and chronic inflammation in NASH patients can lead to hepatocellular carcinoma (HCC). The prevalence of HCC is higher in males than in females, and genetic studies have identified androgen and androgen receptors (ARs) as partially responsible for the gender disparity in the development of liver disease and HCC. Although many factors are known to play important roles in the progression of inflammation in NASH patients, the role of androgen and AR in the progression of NASH to HCC has been understudied. This review summarizes the evidence for a potential role of androgen and the AR pathway in the development of NASH-related HCC and in the treatment of HCC. It has been proposed that AR plays a role in the progression of HCC: inhibitory roles in early stages of hepatocarcinogenesis and tumor-promoting roles in advanced stages. AR can be activated by several pathways, even in the absence of androgen. While AR has been explored as a potential therapeutic target in HCC, several clinical trials have failed to demonstrate a clinical benefit of antiandrogen drugs in HCC. This review discusses the potential reason for these observations and discuss the potential future trials design in this important setting. PMID:28424556

  17. Prevention of Hepatic Fibrosis in a Murine Model of Metabolic Syndrome with Nonalcoholic Steatohepatitis

    PubMed Central

    DeLeve, Laurie D.; Wang, Xiangdong; Kanel, Gary C.; Atkinson, Roscoe D.; McCuskey, Robert S.

    2008-01-01

    The endocannabinoid pathway plays an important role in the regulation of appetite and body weight, hepatic lipid metabolism, and fibrosis. Blockade of the endocannabinoid receptor CB1 with SR141716 promotes weight loss, reduces hepatocyte fatty acid synthesis, and is antifibrotic. D-4F, an apolipoprotein A-1 mimetic with antioxidant properties, is currently in clinical trials for the treatment of atherosclerosis. C57BL/6J mice were fed a high-fat diet for 7 months, followed by a 2.5-month treatment with either SR141716 or D-4F. SR141716 markedly improved body weight, liver weight, serum transaminases, insulin resistance, hyperglycemia, hypercholesterolemia, hyperleptinemia, and oxidative stress, accompanied by the significant prevention of fibrosis progression. D-4F improved hypercholesterolemia and hyperleptinemia without improvement in body weight, steatohepatitis, insulin resistance, or oxidative stress, and yet, there was significant prevention of fibrosis. D-4F prevented culture-induced activation of stellate cells in vitro. In summary, C57BL/6J mice given a high-fat diet developed features of metabolic syndrome with nonalcoholic steatohepatitis and fibrosis. Both SR141716 and D-4F prevented progression of fibrosis after onset of steatohepatitis, ie, a situation comparable to a common clinical scenario, with D-4F seeming to have a more general antifibrotic effect. Either compound therefore has the potential to be of clinical benefit. PMID:18772330

  18. Productive life including all lactations and longer lactations with diminishing credits.

    PubMed

    VanRaden, P M; Dematawewa, C M B; Pearson, R E; Tooker, M E

    2006-08-01

    Alternative measures of productive life (PL) were compared, and life expectancy factors were updated to replace estimates from 1993. Alternatives were proposed with extra credits for lactations longer than 10 mo and beyond 84 mo of age and for each calving so that an extremely long lactation would not receive more credits than multiple shorter lactations with dry periods between. Maximum credits per lactation of 10 mo (original PL), 12 mo, and unlimited were compared. The unlimited credits option either included or excluded a calf value equal to 2 mo of production and had credits given for all days either uniformly or based on lactation curves (diminishing credits). Standard lactation curves (first, second, and greater lactations) were estimated based on the test-day yields of Holstein cows remaining in lactation from a set of 903,579 lactation records. For the diminishing credits alternative, credit for a given day of a parity was derived using the predicted yield of the day proportional to the average daily yield of the first 305 d of second parity. Daily yields were deviations from a baseline of 13.62 kg. Heritabilities and genetic correlations were estimated by multitrait REML for alternative measures of PL, for longevity censored at various ages, and for yield traits and SCS in first parity. Data for REML analysis included records from 1,098,329 Holsteins born from 1994 through 1997 from 5,109 sires, and a relationship matrix among sires was included in the model. Lactations beyond 84 mo added little information. Heritability of PL was 0.073 with 10 mo, 0.069 with 12 mo, 0.068 and 0.067 with unlimited (uniform) lactation credits (with and without calf credits, respectively), and 0.070 with unlimited diminishing credits. Corresponding correlations among predicted transmitting abilities for PL and protein yield were 0.07, 0.06, 0.12, 0.23, and 0.09, all much lower than the 0.46 estimated in 1993. Heritability of PL with diminishing credits improved from 0.017 to

  19. Effect of metformin on ballooning degeneration in nonalcoholic steatohepatitis (NASH): when to use metformin in nonalcoholic fatty liver disease (NAFLD).

    PubMed

    Doycheva, Iliana; Loomba, Rohit

    2014-01-01

    The key histologic feature of nonalcoholic steatohepatitis (NASH) is hepatocellular ballooning (HB). It plays an important role in NASH progression and is an independent predictor of liver mortality. In this review, we identified all studies using metformin in the treatment of nonalcoholic fatty liver disease (NAFLD) that included pre- and post-treatment liver biopsies. We specifically reviewed the effects of metformin on HB. Improved HB was noted in pediatric populations and in those adult patients who were able to lose weight and improve or normalize transaminases during therapy. Previous studies have supported the beneficial effects of metformin in reduction of body weight, improvement of insulin resistance, prevention of complications related to diabetes and chemo-preventive benefits in reducing hepatocellular carcinoma. All these effects make it an attractive treatment consideration for patients with diabetes, and prediabetes who have co-existing NAFLD. Future studies are warranted in order to confirm this effect of metformin on HB and its association with improving long-term outcomes in patients with NAFLD.

  20. Novel Membrane Based Process for Producing Lactate Esters

    SciTech Connect

    1999-02-01

    Lactate Esters from Renewable Carbohydrate Feedstocks can Replace Petroleum-Derived Solvents. Lactate esters are versatile solvents that are biodegradable, nontoxic, and applicable to a wide range of industrial and consumer uses.

  1. LactMed: New NLM Database on Drugs and Lactation

    MedlinePlus

    ... Issues Research News From NIH LactMed: New NLM Database on Drugs and Lactation Past Issues / Summer 2006 ... Javascript on. Photo: Comstock LactMed, a free online database with information on drugs and lactation, is one ...

  2.  Most overweight and obese Indian children have nonalcoholic fatty liver disease.

    PubMed

    Pawar, Sunil V; Zanwar, Vinay G; Choksey, Ajay S; Mohite, Ashok R; Jain, Samit S; Surude, Ravindra G; Contractor, Qais Q; Rathi, Pravin M; Verma, Ravi U; Varthakavi, Premlata K

     Background and rationale. Nonalcoholic fatty liver disease (NAFLD) is the most common cause of pediatric liver disease in western countries. Its prevalence in Indian subcontinent is not well studied.

  3. Insights from Genome-Wide Association Analyses of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Kahali, Bratati; Halligan, Brian; Speliotes, Elizabeth K.

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is caused by hepatic steatosis, which can progress to nonalcoholic steatohepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma in the absence of excessive alcohol consumption. Nonalcoholic fatty liver disease will become the number one cause of liver disease worldwide by 2020. Nonalcoholic fatty liver disease is correlated albeit imperfectly with obesity and other metabolic diseases such as diabetes, hyperlipidemia, and cardiovascular disease, but exactly how having one of these diseases contributes to the development of other metabolic diseases is only now being elucidated. Development of NAFLD and related metabolic diseases is genetically influenced in the population, and recent genome-wide association studies (GWASs) have discovered genetic variants that associate with these diseases. These GWAS-associated variants cannot only help us to identify individuals at high risk of developing NAFLD, but also to better understand its pathophysiology so that we can develop more effective treatments for this disease and related metabolic diseases in the future. PMID:26676813

  4. [Retinal and carotid changes in non-alcoholic fatty liver disease].

    PubMed

    Baloşeanu, Cristina; Rogoveanu, I; Mocanu, Carmen

    2013-01-01

    This article presents the results of a study on 85 patients with non-alcoholic fatty liver disease (NAFLD). We evaluate the retinal vascular changes using retinal photography and carotid vascular changes, by ultrasounds, occured in this group of patients.

  5. Lactate versus pH levels in fetal scalp blood during labor--using the Lactate Scout System.

    PubMed

    Rørbye, Christina; Perslev, Anette; Nickelsen, Carsten

    2016-01-01

    To assess if lactate measured with the Scout Lactate System is a reliable alternative to pH in intrapartum monitoring of the fetus. A prospective study analyzing (1) the correlation between scalp lactate measured by the Scout Lactate System and the Automatic Blood Laboratory (ABL), (2) the correlation between lactate and pH measured in scalp blood and (3) the correlation between fetal scalp lactate and umbilical cord SBE. The sensitivity/specificity and positive/negative predictive values of lactate in predicting low pH were analyzed and expressed as Receiver Operating Curves (ROC). Lactate measured by the Scout Lactate System and the ABL correlated well (r(2)=0.85). Both lactate and pH were measured in 1009 scalp blood samples. The sensitivity and specificity of lactate ≥ 4.8 mmol/l in predicting a pH <7.20 were 0.63 and 0.85, respectively. The correlation between scalp lactate measured within 15 min prior to delivery and the umbilical cord SBE was low. Monitoring non-reassuring deliveries with scalp lactate instead of pH would have resulted in more (155 instead of 56) instrumental deliveries with no decrease in newborns with severe metabolic acidosis.

  6. Nutritional Guide for Pregnant and Lactating Adolescents.

    ERIC Educational Resources Information Center

    Gelbard, Nancy

    Designed to provide accurate and up-to-date information about nutrition and health, this booklet is centered on the nutritional needs of pregnant and lactating adolescents and on the role of schools and the California State Department of Education in meeting those needs. The first section presents information for pregnant adolescents regarding…

  7. Microbial production of lactate-containing polyesters

    PubMed Central

    Yang, Jung Eun; Choi, So Young; Shin, Jae Ho; Park, Si Jae; Lee, Sang Yup

    2013-01-01

    Due to our increasing concerns on environmental problems and limited fossil resources, biobased production of chemicals and materials through biorefinery has been attracting much attention. Optimization of the metabolic performance of microorganisms, the key biocatalysts for the efficient production of the desired target bioproducts, has been achieved by metabolic engineering. Metabolic engineering allowed more efficient production of polyhydroxyalkanoates, a family of microbial polyesters. More recently, non-natural polyesters containing lactate as a monomer have also been produced by one-step fermentation of engineered bacteria. Systems metabolic engineering integrating traditional metabolic engineering with systems biology, synthetic biology, protein/enzyme engineering through directed evolution and structural design, and evolutionary engineering, enabled microorganisms to efficiently produce natural and non-natural products. Here, we review the strategies for the metabolic engineering of microorganisms for the in vivo biosynthesis of lactate-containing polyesters and for the optimization of whole cell metabolism to efficiently produce lactate-containing polyesters. Also, major problems to be solved to further enhance the production of lactate-containing polyesters are discussed. PMID:23718266

  8. 21 CFR 582.5311 - Ferrous lactate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ferrous lactate. 582.5311 Section 582.5311 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...

  9. Biomonitoring Polybrominated Diphenyl Ethers in Lactating Women

    USDA-ARS?s Scientific Manuscript database

    Breast milk is a valuable biological specimen for biomonitoring lipid-soluble polybrominated diphenyl ethers (PBDEs). The goal of this project was to determine the levels of PBDEs in breast milk of lactating women from the Seacoast region of New Hampshire and to examine potential relationships betw...

  10. Studying Reliability Using Identical Handheld Lactate Analyzers

    ERIC Educational Resources Information Center

    Stewart, Mark T.; Stavrianeas, Stasinos

    2008-01-01

    Accusport analyzers were used to generate lactate performance curves in an investigative laboratory activity emphasizing the importance of reliable instrumentation. Both the calibration and testing phases of the exercise provided students with a hands-on opportunity to use laboratory-grade instrumentation while allowing for meaningful connections…

  11. Non-Alcoholic Fatty Pancreas Disease Pathogenesis: A Role for Developmental Programming and Altered Circadian Rhythms

    PubMed Central

    Carter, Rebeca; Mouralidarane, Angelina; Soeda, Junpei; Ray, Shuvra; Pombo, Joaquim; Saraswati, Ruma; Novelli, Marco; Fusai, Giuseppe; Rappa, Francesca; Saracino, Chiara; Pazienza, Valerio; Poston, Lucilla; Taylor, Paul D.; Vinciguerra, Manlio; Oben, Jude A.

    2014-01-01

    Objectives Emerging evidence suggests that maternal obesity (MO) predisposes offspring to obesity and the recently described non-alcoholic fatty pancreas disease (NAFPD) but involved mechanisms remain unclear. Using a pathophysiologically relevant murine model, we here investigated a role for the biological clock - molecular core circadian genes (CCG) in the generation of NAFPD. Design Female C57BL6 mice were fed an obesogenic diet (OD) or standard chow (SC) for 6 weeks, prior to pregnancy and throughout gestation and lactation: resulting offspring were subsequently weaned onto either OD (Ob_Ob and Con_Ob) or standard chow (Ob_Con and Con_Con) for 6 months. Biochemical, pro-inflammatory and pro-fibrogenic markers associated with NAFPD were then evaluated and CCG mRNA expression in the pancreas determined. Results Offspring of obese dams weaned on to OD (Ob_Ob) had significantly increased (p≤0.05): bodyweight, pancreatic triglycerides, macrovesicular pancreatic fatty-infiltration, and pancreatic mRNA expression of TNF-α, IL-6, α-SMA, TGF-β and increased collagen compared to offspring of control dams weaned on to control chow (Con_Con). Analyses of CCG expression demonstrated a phase shift in CLOCK (−4.818, p<0.01), REV-ERB-α (−1.4,p<0.05) and Per2 (3.27,p<0.05) in association with decreased amplitude in BMAL-1 (−0.914,p<0.05) and PER2 (1.18,p<0.005) in Ob_Ob compared to Con_Con. 2-way ANOVA revealed significant interaction between MO and post-weaning OD in expression of CLOCK (p<0.005), PER1 (p<0.005) and PER2 (p<0.05) whilst MO alone influenced the observed rhythmic variance in expression of all 5 measured CCG. Conclusions Fetal and neonatal exposure to a maternal obesogenic environment interacts with a post-natal hyper-calorific environment to induce offspring NAFPD through mechanisms involving perturbations in CCG expression. PMID:24657938

  12. Myocardial metabolism during hypoxia: Maintained lactate oxidation during increased glycolysis

    SciTech Connect

    Mazer, C.D.; Stanley, W.C.; Hickey, R.F.; Neese, R.A.; Cason, B.A.; Demas, K.A.; Wisneski, J.A.; Gertz, E.W. )

    1990-09-01

    In the intact animal, myocardial lactate utilization and oxidation during hypoxia are not well understood. Nine dogs were chronically instrumented with flow probes on the left anterior descending coronary artery and with a coronary sinus sampling catheter. ({sup 14}C)lactate and ({sup 13}C)glucose tracers, or ({sup 13}C)lactate and ({sup 14}C)glucose were administered to quantitate lactate and glucose oxidation, lactate conversion to glucose, and simultaneous lactate extraction and release. The animals were anesthetized and exposed to 90 minutes of severe hypoxia (PO2 = 25 +/- 4 torr). Hypoxia resulted in significant increases in heart rate, cardiac output and myocardial blood flow, but no significant change in myocardial oxygen consumption. The arterial/coronary sinus differences for glucose and lactate did not change from normoxia to hypoxia; however, the rate of glucose uptake increased significantly due to the increase in myocardial blood flow. Tracer-measured lactate extraction did not decrease with hypoxia, despite a 250% increase in lactate release. During hypoxia, 90% +/- 4% of the extracted {sup 14}C-lactate was accounted for by the appearance of {sup 14}CO{sub 2} in the coronary sinus, compared with 88% +/- 4% during normoxia. Thus, in addition to the expected increase in glucose uptake and lactate production, we observed an increase in lactate oxidation during hypoxia.

  13. Cloning and nucleotide sequence of the Lactobacillus casei lactate dehydrogenase gene.

    PubMed Central

    Kim, S F; Baek, S J; Pack, M Y

    1991-01-01

    An allosteric L-(+)-lactate dehydrogenase gene of Lactobacillus casei ATCC 393 was cloned in Escherichia coli, and the nucleotide sequence of the gene was determined. The gene was composed of an open reading frame of 981 bp, starting with a GTG codon and ending with a TAA codon. The sequences for the promoter and ribosome binding site were identified, and a sequence for a structure resembling a rho-independent transcription terminator was also found. Images PMID:1768113

  14. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research.

    PubMed

    Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Crespo Yanguas, Sara; Colle, Isabelle; Van Den Bossche, Bert; Da Silva, Tereza Cristina; de Oliveira, Cláudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini; Cogliati, Bruno; Vinken, Mathieu

    2015-07-01

    Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and '-omics'-based read-outs are still in their infancy, but show great promise. In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed.

  15. 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

  16. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research

    PubMed Central

    Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Yanguas, Sara Crespo; Colle, Isabelle; Van Den Bossche, Bert; Da silva, Tereza Cristina; Oliveira, Cláudia P; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Cogliati, Bruno; Vinken, Mathieu

    2015-01-01

    Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and ‘-omics’-based read-outs are still in their infancy, but show great promise. . In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. PMID:26073454

  17. The lactate minimum test for cycling: estimation of the maximal lactate steady state.

    PubMed

    MacIntosh, Brian R; Esau, Shane; Svedahl, Krista

    2002-06-01

    This study evaluated the reliability and validity of the lactate minimum test (LMT), an incremental test given after lactic acidosis was induced by sprint exercise. This test is purported to accurately estimate the intensity of exercise at which the transport of lactate into and out of the blood is in equilibrium (maximal lactate steady state or MLSS) and should be a good predictor of endurance performance. Fourteen athletes (mean age 27.2 +/- 3.7 yrs) completed the following on Kreitler rollers: (a) two 20-km time-trials (35.1 +/- 3.3 and 35.7 +/- 3.5 km.hr-1, p < .05); (b) two LMTs yielding lactate minimum speeds (LMS) of 33.6 +/- 3.4 and 33.4 +/- 3.1 km.hr-1 (p > 0.6); and (c) four constant intensity rides, at speeds bracketing the LMS. At 33.5 +/- 3.1 km.hr-1 plasma lactate concentration decreased 0.4 +/- 1.6 mM from 10 to 30 min. Plasma lactate increased 1.6 +/- 0.7 mM while riding 0.9 +/- 0.9 km.hr-1 faster. The LMT is a reliable (r2 = 0.904) and valid method to predict MLSS and a good predictor of endurance performance (LMT vs. 20-km time-trial, r2 = 0.86).

  18. Genetic polymorphisms in non-alcoholic fatty liver disease in obese Egyptian children.

    PubMed

    El-Koofy, Nehal M; El-Karaksy, Hanaa M; Mandour, Iman M; Anwar, Ghada M; El-Raziky, Mona S; El-Hennawy, Ahmad M

    2011-01-01

    Polymorphisms in the promoter of microsomal triglyceride transfer protein (MTP) lead to decreased MTP transcription, less export of triglyceride from hepatocytes, and greater intracellular triglyceride accumulation. Therefore, functional polymorphisms in MTP may be involved in determining susceptibility to nonalcoholic steatohepatitis (NASH). The aim of this study is to examine the effect of some genetic influences among a group of obese Egyptian children. A cross-sectional study was conducted on 76 overweight and obese children presenting to the Pediatric Endocrinology Unit, Cairo University Children's Hospital, Egypt, as well as on 20 healthy controls. Anthropometric measurements were taken for all the patients and they underwent clinical examination, ultrasonographic examination of the liver, and liver biopsy when appropriate. Liver functions, blood glucose, serum insulin, C-peptide, and lipid profile were assessed and HOMA-IR calculated. Blood samples from biopsy-proven NASH patients and controls were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism for the -493 G/T polymorphism in the promoter of MTP and the 1183 T/C polymorphism in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD). Eight had biopsy-proven simple steatosis and 7 had NASH. NASH patients had a much higher incidence of the MTP G/G genotype (P = 0.002, CI: 2.9-392) compared with the controls. NASH patients also had a 100% prevalence of the MnSOD T/T genotype. Certain genotypes in MTP and MnSOD are significantly more prevalent among obese children with NASH and may be responsible for such a phenotype.

  19. Osteopontin is a proximal effector of leptin-mediated non-alcoholic steatohepatitis (NASH) fibrosis

    PubMed Central

    Coombes, Jason D.; Choi, Steve S.; Swiderska-Syn, Marzena; Manka, Paul P.; Reid, Danielle; Palma, Elena; Briones-Orta, Marco A.; Xie, Guanhua; Younis, Rasha; Kitamura, Naoto; Peruta, Marco della; Bitencourt, Shanna; Dollé, Laurent; Oo, Ye Htun; Mi, Zhiyong; Kuo, Paul C.; Williams, Roger; Chokshi, Shilpa; Canbay, Ali; Claridge, Lee C.; Eksteen, Bertus; Diehl, Anna Mae; Syn, Wing-Kin

    2016-01-01

    Introduction Liver fibrosis develops when hepatic stellate cells (HSC) are activated into collagen-producing myofibroblasts. In non-alcoholic steatohepatitis (NASH), the adipokine leptin is upregulated, and promotes liver fibrosis by directly activating HSC via the hedgehog pathway. We reported that hedgehog-regulated osteopontin (OPN) plays a key role in promoting liver fibrosis. Herein, we evaluated if OPN mediates leptin-profibrogenic effects in NASH. Methods Leptin-deficient (ob/ob) and wild-type (WT) mice were fed control or methionine-choline deficient (MCD) diet. Liver tissues were assessed by Sirius-red, OPN and αSMA IHC, and qRT-PCR for fibrogenic genes. In vitro, HSC with stable OPN (or control) knockdown were treated with recombinant (r)leptin and OPN-neutralizing or sham-aptamers. HSC response to OPN loss was assessed by wound healing assay. OPN-aptamers were also added to precision-cut liver slices (PCLS), and administered to MCD-fed WT (leptin-intact) mice to determine if OPN neutralization abrogated fibrogenesis. Results MCD-fed WT mice developed NASH-fibrosis, upregulated OPN, and accumulated αSMA+ cells. Conversely, MCD-fed ob/ob mice developed less fibrosis and accumulated fewer αSMA+ and OPN+ cells. In vitro, leptin-treated HSC upregulated OPN, αSMA, collagen 1α1 and TGFβ mRNA by nearly 3-fold, but this effect was blunted by OPN loss. Inhibition of PI3K and transduction of dominant negative-Akt abrogated leptin-mediated OPN induction, while constitutive active-Akt upregulated OPN. Finally, OPN neutralization reduced leptin-mediated fibrogenesis in both PCLS and MCD-fed mice. Conclusion OPN overexpression in NASH enhances leptin-mediated fibrogenesis via PI3K/Akt. OPN neutralization significantly reduces NASH fibrosis, reinforcing the potential utility of targeting OPN in the treatment of patients with advanced NASH. PMID:26529285

  20. Genetic Polymorphisms in Non-alcoholic Fatty Liver Disease in Obese Egyptian Children

    PubMed Central

    El-Koofy, Nehal M.; El-Karaksy, Hanaa M.; Mandour, Iman M.; Anwar, Ghada M.; El-Raziky, Mona S.; El-Hennawy, Ahmad M.

    2011-01-01

    Background/Aim: Polymorphisms in the promoter of microsomal triglyceride transfer protein (MTP) lead to decreased MTP transcription, less export of triglyceride from hepatocytes, and greater intracellular triglyceride accumulation. Therefore, functional polymorphisms in MTP may be involved in determining susceptibility to nonalcoholic steatohepatitis (NASH). The aim of this study is to examine the effect of some genetic influences among a group of obese Egyptian children. Patients and Methods: A cross-sectional study was conducted on 76 overweight and obese children presenting to the Pediatric Endocrinology Unit, Cairo University Children's Hospital, Egypt, as well as on 20 healthy controls. Anthropometric measurements were taken for all the patients and they underwent clinical examination, ultrasonographic examination of the liver, and liver biopsy when appropriate. Liver functions, blood glucose, serum insulin, C-peptide, and lipid profile were assessed and HOMA-IR calculated. Blood samples from biopsy-proven NASH patients and controls were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism for the –493 G/T polymorphism in the promoter of MTP and the 1183 T/C polymorphism in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD). Results: Eight had biopsy-proven simple steatosis and 7 had NASH. NASH patients had a much higher incidence of the MTP G/G genotype (P = 0.002, CI: 2.9–392) compared with the controls. NASH patients also had a 100% prevalence of the MnSOD T/T genotype. Conclusion: Certain genotypes in MTP and MnSOD are significantly more prevalent among obese children with NASH and may be responsible for such a phenotype. PMID:21727734

  1. Role of bioactive fatty acids in nonalcoholic fatty liver disease.

    PubMed

    Juárez-Hernández, Eva; Chávez-Tapia, Norberto C; Uribe, Misael; Barbero-Becerra, Varenka J

    2016-08-02

    Nonalcoholic fatty liver disease (NAFLD) is characterized by fat deposition in hepatocytes, and a strong association with nutritional factors. Dietary fatty acids are classified according to their biochemical properties, which confer their bioactive roles. Monounsaturated fatty acids have a dual role in various human and murine models. In contrast, polyunsaturated fatty acids exhibit antiobesity, anti steatosic and anti-inflammatory effects. The combination of these forms of fatty acids-according to dietary type, daily intake and the proportion of n-6 to n-3 fats-can compromise hepatic lipid metabolism. A chemosensory rather than a nutritional role makes bioactive fatty acids possible biomarkers for NAFLD. Bioactive fatty acids provide health benefits through modification of fatty acid composition and modulating the activity of liver cells during liver fibrosis. More and better evidence is necessary to elucidate the role of bioactive fatty acids in nutritional and clinical treatment strategies for patients with NAFLD.

  2. Perception of self and significant others by alcoholics and nonalcoholics.

    PubMed

    Quereshi, M Y; Soat, D M

    1976-01-01

    Ratings of self and 15 significant others on four personality factors by 47 alcoholic and 90 nonalcoholic males were analyzed by means of step-wise regression analysis and multivariate analysis of covariance. Alcoholics rated themselves less positively on extraversion and self-assertiveness (lower mean on extraversion and higher on self-assertiveness) and also judged intimate others (father, mother, and spouse) less positively on unhappiness, extraversion, and productive persistence (higher mean on unhappiness and lower means on extraversion and productive persistence). There were no significant differences between the two groups in judging persons as a whole or in the degree of differentiation that was exhibited in rating all 16 persons including self.

  3. Lipoprotein Metabolism, Dyslipidemia and Nonalcoholic Fatty Liver Disease

    PubMed Central

    Cohen, David E.; Fisher, Edward A.

    2014-01-01

    Cardiovascular disease represents the most common cause of death in patients with non-alcoholic fatty liver disease (NAFLD). NAFLD patients exhibit an atherogenic dyslipidemia that is characterized by an increased plasma concentration of triglycerides, reduced concentration of high density lipoprotein (HDL) cholesterol, and low density lipoprotein (LDL) particles that are smaller and more dense than normal. The pathogenesis of NAFLD-associated atherogenic dyslipidemia is multifaceted, but many aspects are attributable to manifestations of insulin resistance. Here we review the structure, function and metabolism of lipoproteins, which are macromolecular particles of lipids and proteins that transport otherwise insoluble triglyceride and cholesterol molecules within the plasma. We provide a current explanation of the metabolic perturbations that are observed in the setting of insulin resistance. An improved understanding of the pathophysiology of atherogenic dyslipidemia would be expected to guide therapies aimed at reducing morbidity and mortality in NAFLD patients. PMID:24222095

  4. Non-alcoholic fatty liver disease: A poorly known pandemic.

    PubMed

    Augustin, Salvador; Graupera, Isabel; Caballeria, Juan

    2017-07-24

    Non-alcoholic fatty liver disease (NAFLD) consists of an excessive depositing of fat in the liver, which can end up by causing inflammation, fibrosis and also cirrhosis with the corresponding complications including liver cancer. NAFLD has become the most common liver disease worldwide. The incidence has increased in parallel with the obesity, diabetes and metabolic syndrome epidemic, thus resulting in becoming one of the main indications for liver transplant. The diagnosis has principally been through histology but with the development of non-invasive methods, these have helped in simplifying the management of these patients in clinical practice. The only therapeutic strategies currently available are focused on weight loss (lifestyle changes or bariatric surgery). There is still no approved pharmacological option for the treatment of NAFLD, however there are a number of molecular studies in advanced stages of development. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  5. Non-alcoholic Fatty Liver Disease: East Versus West

    PubMed Central

    Agrawal, Swastik; Duseja, Ajay K

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver disease worldwide with prevalence ranging from 10% to 30% in various countries. It has become an important cause of unexplained rise in transaminases, cryptogenic cirrhosis, and cryptogenic hepatocellular carcinoma. Pathogenesis is related to obesity, insulin resistance, oxidative stress, lipotoxicity, and resultant inflammation in the liver progressing to fibrosis. Pharmacological treatment in patients with NAFLD is still evolving and the treatment of these patients rests upon lifestyle modification with diet and exercise being the cornerstones of therapy. While there are many similarities between patients with NAFLD from Asia and the West, there are certain features which make the patients with NAFLD from Asia stand apart. This review highlights the data on NAFLD from Asia comparing it with the data from the West. PMID:25755421

  6. A concise review of non-alcoholic fatty liver disease.

    PubMed

    Than, Nwe Ni; Newsome, Philip N

    2015-03-01

    Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and the incidence of which is rising rapidly due to the increasing epidemic of obesity in both adults and children. The initial accumulation of fat followed by subsequent inflammation is central to the development of liver damage, and is critically influenced by host factors including age, gender, presence of diabetes, genetic polymorphisms and more recently by the gut microbiome. An increasing body of data suggest that NAFLD is also an independent risk factor of cardiovascular disease, which remains the commonest cause of mortality in such patients. This review focusses on the pathogenesis of NAFLD, and the evolution of new approaches to the management and treatment of NAFLD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Glycosyltransferases and non-alcoholic fatty liver disease

    PubMed Central

    Zhan, Yu-Tao; Su, Hai-Ying; An, Wei

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease and its incidence is increasing worldwide. However, the underlying mechanisms leading to the development of NAFLD are still not fully understood. Glycosyltransferases (GTs) are a diverse class of enzymes involved in catalyzing the transfer of one or multiple sugar residues to a wide range of acceptor molecules. GTs mediate a wide range of functions from structure and storage to signaling, and play a key role in many fundamental biological processes. Therefore, it is anticipated that GTs have a role in the pathogenesis of NAFLD. In this article, we present an overview of the basic information on NAFLD, particularly GTs and glycosylation modification of certain molecules and their association with NAFLD pathogenesis. In addition, the effects and mechanisms of some GTs in the development of NAFLD are summarized. PMID:26937136

  8. Glycosyltransferases and non-alcoholic fatty liver disease.

    PubMed

    Zhan, Yu-Tao; Su, Hai-Ying; An, Wei

    2016-02-28

    Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease and its incidence is increasing worldwide. However, the underlying mechanisms leading to the development of NAFLD are still not fully understood. Glycosyltransferases (GTs) are a diverse class of enzymes involved in catalyzing the transfer of one or multiple sugar residues to a wide range of acceptor molecules. GTs mediate a wide range of functions from structure and storage to signaling, and play a key role in many fundamental biological processes. Therefore, it is anticipated that GTs have a role in the pathogenesis of NAFLD. In this article, we present an overview of the basic information on NAFLD, particularly GTs and glycosylation modification of certain molecules and their association with NAFLD pathogenesis. In addition, the effects and mechanisms of some GTs in the development of NAFLD are summarized.

  9. Nonalcoholic fatty liver disease: the concept and confusion.

    PubMed

    Sanal, M G

    2011-12-01

    Nonalcoholic fatty liver disease (NAFLD) is generally considered as a disease associated with diabetes mellitus type 2. But on a closer evaluation we realize a host of confusion associated with this from the nomenclature, diagnosis to pathogenesis. The term refers to a spectrum ranging from steatosis to steatosis with inflammation (NASH) to cirrhosis in the absence of alcohol abuse. But in fact NAFLD is a vague term for a spectrum of diseases which differ not only in the clinical presentation but also in the etiology. NAFLD is loose to incorporate so many etiologies excluding alcoholism and few other "known" etiologies, presenting as fat in liver. Considering the diverse etiologies there is a need for personalized management in NAFLD, which at present is difficult. Currently fatty liver disease could be considered as an added Hepato-cardiovascular-renal and cancer risk factor rather than a specific diagnosis.

  10. Nutrition and Physical Activity in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Oliveira, Claudia P.; de Lima Sanches, Priscila; de Abreu-Silva, Erlon Oliveira; Marcadenti, Aline

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and it is associated with other medical conditions such as diabetes mellitus, metabolic syndrome, and obesity. The mechanisms of the underlying disease development and progression are not completely established and there is no consensus concerning the pharmacological treatment. In the gold standard treatment for NAFLD weight loss, dietary therapy, and physical activity are included. However, little scientific evidence is available on diet and/or physical activity and NAFLD specifically. Many dietary approaches such as Mediterranean and DASH diet are used for treatment of other cardiometabolic risk factors such as insulin resistance and type-2 diabetes mellitus (T2DM), but on the basis of its components their role in NAFLD has been discussed. In this review, the implications of current dietary and exercise approaches, including Brazilian and other guidelines, are discussed, with a focus on determining the optimal nonpharmacological treatment to prescribe for NAFLD. PMID:26770987

  11. Non-alcoholic steatohepatitis in morbidly obese patients.

    PubMed

    Tran, Albert; Gual, Philippe

    2013-02-01

    The hepatic complications of morbid obesity range from steatosis to steatohepatitis (Non-alcoholic steatohepatitis [NASH]), fibrosis, cirrhosis and finally hepatocellular carcinoma. The pathophysiological mechanisms of the progression of a normal liver to a liver showing steatosis and then steatohepatitis are complex, including, per se, insulin-resistance, iron accumulation, oxidative stress and hepatocyte death. An imbalance in anti- and pro-inflammatory factors may be the trigger. These factors can originate from intra- or extrahepatic sites, particularly the adipose tissue and the gut. This review will provide insight into the current diagnosis and understanding of hepatic inflammation including non-invasive markers of NASH (markers of hepatocyte death), intrahepatic mechanisms (regulation of the immune and inflammatory response, hepatocellular iron deposition, hepatocyte death) and extrahepatic factors (from adipose tissue and gut) in morbidly obese patients. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  12. Immunological Mechanisms in the Pathophysiology of Non-Alcoholic Steatohepatitis

    PubMed Central

    Vonghia, Luisa; Michielsen, Peter; Francque, Sven

    2013-01-01

    Non-alcoholic steatohepatitis (NASH) is characterized by the presence of steatosis, inflammation and hepatocyte injury and constitutes hepatic manifestation of the metabolic syndrome. The pathogenesis of NASH is complex and implicates cross-talk between different metabolically active sites, such as liver and adipose tissue. Obesity is considered a chronic low-grade inflammatory state and the liver has been recognized as being an “immunological organ”. The complex role of the immune system in the pathogenesis of NASH is currently raising great interest, also in view of the possible therapeutic potential of immunotherapy in NASH. This review focuses on the disturbances of the cells constituting the innate and adaptive immune system in the liver and in adipose tissue. PMID:24084730

  13. Nonalcoholic fatty liver disease and low-carbohydrate diets.

    PubMed

    York, Linda Wasserbach; Puthalapattu, Swathy; Wu, George Y

    2009-01-01

    Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance, obesity, and other features of metabolic syndrome and is known to be the most common cause for abnormal liver enzymes. The recent surge in the number of patients with NAFLD has been accompanied by an increase in research on potential treatment options, particularly weight loss and dietary interventions. Given the growing interest on the role of carbohydrates in the prevention and treatment of NAFLD, this review discusses the relationship between the amount of carbohydrates in the diet and effects on NAFLD, with special emphasis on a low-carbohydrate diet. We discuss the role of insulin resistance in the pathophysiology of NAFLD and provide an overview of various popular diets and their role as a treatment option for NAFLD. Additional large, longer-duration trials studying the efficacy of a low-carbohydrate diet in the treatment and prevention of NAFLD are eagerly awaited.

  14. Microbiology of 'obiolor': a Nigerian fermented non-alcoholic beverage.

    PubMed

    Achi, O K

    1990-09-01

    Obiolor is an acidic non-alcoholic beverage prepared by fermenting sorghum and millet malts. The traditional process for the production and microbiological characteristics of the beverage were investigated. Bacillus spp., Lactobacillus plantarum and Streptococcus lactis were the associated micro-organisms most actively involved. Yeasts were present in low numbers towards the end of the fermentation. Other micro-organisms isolated did not appear to play a role in the fermentation process. Variations in the important microbial groups involved and their metabolic products were studied. Titratable acidity increased gradually until the end of the fermentation while the total soluble solids and pH declined. Acetobacter spp. were probably responsible for the unacceptability of the product after 24 h.

  15. Circulating microRNAs in nonalcoholic fatty liver disease.

    PubMed

    DiStefano, Johanna K; Gerhard, Glenn S

    2016-01-01

    Liver biopsy is currently recognized as the most accurate method for diagnosing and staging nonalcoholic fatty liver disease (NAFLD). However, this procedure is typically performed when disease has progressed to clinically significant stages, thereby limiting early diagnosis of patients who are at high risk for development of liver- and cardiovascular-related morbidity and mortality. Recently, microRNAs (miRNAs), short, noncoding RNAs that regulate gene expression, have been associated with histological features of NAFLD and are readily detected in the circulation. As such, miRNAs are emerging as potentially useful noninvasive markers with which to follow the progression of NAFLD. In this article, we present the evidence linking circulating miRNAs with NAFLD and discuss the potential value of circulating miRNA profiles in the development of improved methods for NAFLD diagnosis and clinical monitoring of disease progression.

  16. Circulating microRNAs in nonalcoholic fatty liver disease

    PubMed Central

    Gerhard, Glenn S.

    2016-01-01

    Summary Liver biopsy is currently recognized as the most accurate method for diagnosing and staging nonalcoholic fatty liver disease (NAFLD). However, this procedure is typically performed when disease has progressed to clinically significant stages, thereby limiting early diagnosis of patients who are at high risk for development of liver- and cardiovascular-related morbidity and mortality. Recently, microRNAs (miRNAs), short, noncoding RNAs that regulate gene expression, have been associated with histological features of NAFLD and are readily detected in the circulation. As such, miRNAs are emerging as potentially useful noninvasive markers with which to follow the progression of NAFLD. In this article, we present the evidence linking circulating miRNAs with NAFLD and discuss the potential value of circulating miRNA profiles in the development of improved methods for NAFLD diagnosis and clinical monitoring of disease progression. PMID:26606259

  17. Effect of lactation number, year, and season of initiation of lactation on milk yield of cows hormonally induced into lactation and treated with recombinant bovine somatotropin.

    PubMed

    Mellado, M; Antonio-Chirino, E; Meza-Herrera, C; Veliz, F G; Arevalo, J R; Mellado, J; de Santiago, A

    2011-09-01

    Records representing data from 1,500 barren Holstein cows over an 8-yr period from a large commercial dairy farm in northern Mexico were analyzed to determine the effects of lactation number and season and year of initiation of lactation on milk production of cows induced hormonally into lactation and treated with recombinant bovine somatotropin (rbST) throughout lactation. Peak and 305-d milk yields were also assessed as predictors of total milk yield in cows induced into lactation. A significant quadratic relationship was found between 305-d milk yield and number of lactation [7,607±145 and 9,548±181 kg for first- and ≥6-lactation cows, respectively; mean ± standard error of the mean (SEM)] with the highest production occurring in the fifth lactation. Total milk yields of cows with ≤2 lactations were approximately 4,500 kg less than milk yields of adult cows (the overall average ± standard milk yield was 13,544±5,491 kg per lactation and the average lactation length was 454±154 d). Moreover, 305-d milk production was depressed in cows induced into lactation in spring (8,804±153 kg; mean ± SEM) and summer (8,724±163 kg) than in fall (9,079±151 kg) and winter (9,085±143 kg). Partial regression coefficients for 305-d milk yield and peak milk yield indicated an increment of 157 kg of milk per lactation per 1-kg increase in peak milk yield (r(2)=0.69). Neither peak milk yield (r(2)=0.18) nor 305-d milk yield (r(2)=0.29) was accurate for predicting total milk yield per lactation. Year, parity, and season effects had significant influence on milk yield of cows induced into lactation and treated with rbST throughout lactation, and peak milk yield can assist in the prediction of 305-d milk yield but not total milk yield. This study also showed that hormonal induction of lactation in barren high-yielding cows is a reliable, practical, and affordable technique in countries where rbST treatment and prolonged steroid administration of dairy cows are legally

  18. Pediatric nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular risk.

    PubMed

    Pacifico, Lucia; Nobili, Valerio; Anania, Caterina; Verdecchia, Paola; Chiesa, Claudio

    2011-07-14

    Nonalcoholic fatty liver disease (NAFLD) encompasses a range of liver histology severity and outcomes in the absence of chronic alcohol use. The mildest form is simple steatosis in which triglycerides accumulate within hepatocytes. A more advanced form of NAFLD, non-alcoholic steatohepatitis, includes inflammation and liver cell injury, progressive to cryptogenic cirrhosis. NAFLD has become the most common cause of chronic liver disease in children and adolescents. The recent rise in the prevalence rates of overweight and obesity likely explains the NAFLD epidemic worldwide. NAFLD is strongly associated with abdominal obesity, type 2 diabetes, and dyslipidemia, and most patients have evidence of insulin resistance. Thus, NAFLD shares many features of the metabolic syndrome (MetS), a highly atherogenic condition, and this has stimulated interest in the possible role of NAFLD in the development of atherosclerosis. Accumulating evidence suggests that NAFLD is associated with a significantly greater overall mortality than in the general population, as well as with increased prevalence of cardiovascular disease (CVD), independently of classical atherosclerotic risk factors. Yet, several studies including the pediatric population have reported independent associations between NAFLD and impaired flow-mediated vasodilatation and increased carotid artery intimal medial thickness-two reliable markers of subclinical atherosclerosis-after adjusting for cardiovascular risk factors and MetS. Therefore, the rising prevalence of obesity-related MetS and NAFLD in childhood may lead to a parallel increase in adverse cardiovascular outcomes. In children, the cardiovascular system remains plastic and damage-reversible if early and appropriate interventions are established effectively. Therapeutic goals for NAFLD should address nutrition, physical activity, and avoidance of smoking to prevent not only end-stage liver disease but also CVD.

  19. NASH (Nonalcoholic steatohepatitis): A case of multiorganelle failure.

    PubMed

    Caldwell, Stephen

    2014-10-01

    The clinical term 'multiorgan failure' lends itself, modified to 'multiorganelle failure', to the cascading events in cellular systems leading to hepatocyte injury, cell death, inflammation and fibrosis and ultimately to cirrhosis in NASH (non-alcoholic steatohepatitis). NASH is one of the most common forms of liver disease and constitutes the severe form of NAFLD (non-alcoholic fatty liver disease). The key features that distinguish potentially progressive NASH from relatively stable non-NASH fatty liver (NNFL, often referred to as simple steatosis) are cellular ballooning, inflammation and fibrosis. These findings, together with steatosis or accumulation of greater than normal hepatic lipid, usually constitute histological NASH seen on liver biopsy or in laboratory samples. Cellular ballooning is not specific to NASH but it is perhaps the most emblematic finding on histological samples. The ballooned hepatocyte has evidence of cytoskeletal injury (depletion and condensation as Mallory-Denk bodies), accumulation of partially oxidized small fat droplets, mitochondrial morphological changes presumably related to organelle dysfunction, dilated endoplasmic reticulum and autophagosomes - an attempt at cellular repair. Ballooning itself likely results from a combination of cytoskeletal injury resulting in loss of normal cell shape and from accumulation of injured and somewhat derelict small fat droplets and dilated endoplasmic reticulum. Cellular injury in NASH and especially cellular ballooning can be viewed as a process of 'multi-organelle failure' beginning with generation of super oxide and failure to contain the subsequent oxidative injury and by-products in an environment rich in lipid fuel. These events lead to activation of imunologic pathways. Dysfunction of the small fat droplet appears to be a central mechanism and the oxidative injury can be viewed as the process of rancidification - the chemical decomposition of oils, lipids and fats.

  20. Differential Intrahepatic Phospholipid Zonation in Simple Steatosis and Nonalcoholic Steatohepatitis

    PubMed Central

    Wattacheril, Julia; Seeley, Erin H.; Angel, Peggi; Chen, Heidi; Bowen, Benjamin P.; Lanciault, Christian; M.Caprioli, Richard; Abumrad, Naji; Flynn, Charles Robb

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD) occurs frequently in a setting of obesity, dyslipidemia and insulin resistance, but the etiology of the disease, particularly the events favoring progression to nonalcoholic steatohepatitis (NASH) as opposed to simple steatosis (SS), are not fully understood. Based on known zonation patterns in protein, glucose and lipid metabolism, coupled with evidence that phosphatidylcholine may play a role in NASH pathogenesis, we hypothesized that phospholipid zonation exists in liver and that specific phospholipid abundance and distribution may be associated with histologic disease. A survey of normal hepatic protein expression profiles in the Human Protein Atlas revealed pronounced zonation of enzymes involved in lipid utilization and storage, particularly those facilitating phosphatidylcholine (PC) metabolism. Immunohistochemistry of obese normal, SS and NASH liver specimens with anti-phosphatidylethanomine N-methyltransferase (PEMT) antibodies showed a progressive decrease in the zonal distribution of this PC biosynthetic enzyme. Phospholipid quantitation by liquid chromatography mass spectrometry (LC-MS) in hepatic extracts of Class III obese patients with increasing NAFLD severity revealed that most PC species with 32, 34 and 36 carbons as well as total PC abundance was decreased with SS and NASH. Matrix assisted laser desorption ionization - imaging mass spectrometry (MALDI-IMS) imaging revealed strong zonal distributions for 32, 34 and 36 carbon PCs in controls (minimal histologic findings) and SS that was lo