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  • We present data supporting the hypothesis that the lysosomalautophagy pathway is involved in the degradation of intracellular triacylglycerols in the liver. In primary hepatocytes cultivated in the absence of exogenous fatty acids (FFA), both inhibition of autophagy flux (asparagine) or lysosomal activity (chloroquine) decreased secretion of VLDL (very low density lipoproteins) and formation of FFA oxidative products while the stimulation of autophagy by rapamycine increased some of these parameters. Effect of rapamycine was completely abolished by inactivation of lysosomes. Similarly, when autophagic activity was influenced by cultivating the hepatocytes in ?starving? (amino-acid poor medium) or ?fed? (serum-supplemented medium) conditions,VLDL secretion and FFA oxidation mirrored the changes in autophagy being higher in starvation and lower in fed state. Autophagy inhibition as well as lysosomal inactivation depressed FFA and DAG (diacylglycerol) formation in liver slices in vitro. In vivo, intensity of lysosomal lipid degradation depends on the formation of autophagolysosomes, i.e. structures bringing the substrate for degradation and lysosomal enzymes into contact. We demonstrated that lysosomal lipase (LAL) activity in liver autophagolysosomal fraction was up-regulated in fasting and down-regulated in fed state together with the increased translocation of LAL and LAMP2 proteins from lysosomal pool to this fraction. Changes in autophagy intensity (LC3-II/LC3-I ratio) followed a similar pattern.
  • We present data supporting the hypothesis that the lysosomalautophagy pathway is involved in the degradation of intracellular triacylglycerols in the liver. In primary hepatocytes cultivated in the absence of exogenous fatty acids (FFA), both inhibition of autophagy flux (asparagine) or lysosomal activity (chloroquine) decreased secretion of VLDL (very low density lipoproteins) and formation of FFA oxidative products while the stimulation of autophagy by rapamycine increased some of these parameters. Effect of rapamycine was completely abolished by inactivation of lysosomes. Similarly, when autophagic activity was influenced by cultivating the hepatocytes in ?starving? (amino-acid poor medium) or ?fed? (serum-supplemented medium) conditions,VLDL secretion and FFA oxidation mirrored the changes in autophagy being higher in starvation and lower in fed state. Autophagy inhibition as well as lysosomal inactivation depressed FFA and DAG (diacylglycerol) formation in liver slices in vitro. In vivo, intensity of lysosomal lipid degradation depends on the formation of autophagolysosomes, i.e. structures bringing the substrate for degradation and lysosomal enzymes into contact. We demonstrated that lysosomal lipase (LAL) activity in liver autophagolysosomal fraction was up-regulated in fasting and down-regulated in fed state together with the increased translocation of LAL and LAMP2 proteins from lysosomal pool to this fraction. Changes in autophagy intensity (LC3-II/LC3-I ratio) followed a similar pattern. (en)
Title
  • Autophagy-lysosomal pathway is involved in lipid degradation
  • Autophagy-lysosomal pathway is involved in lipid degradation (en)
skos:prefLabel
  • Autophagy-lysosomal pathway is involved in lipid degradation
  • Autophagy-lysosomal pathway is involved in lipid degradation (en)
skos:notation
  • RIV/00023001:_____/12:00056252!RIV13-MZ0-00023001
http://linked.open...avai/predkladatel
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • P(NS10504)
http://linked.open...iv/cisloPeriodika
  • 3
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
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http://linked.open...titaPredkladatele
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  • 124265
http://linked.open...ai/riv/idVysledku
  • RIV/00023001:_____/12:00056252
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • Autophagy, Lysosomes, Lipolysis, Hepatocyte, Lysosomal lipase (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • CZ - Česká republika
http://linked.open...ontrolniKodProRIV
  • [2780671DCBE1]
http://linked.open...i/riv/nazevZdroje
  • Physiological research
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
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http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 61
http://linked.open...iv/tvurceVysledku
  • Kazdová, Ludmila
  • Baranowski, M.
  • Cahová, Monika
  • Daňková, Helena
  • Papáčková, Zuzana
  • Páleníčková, Eliška
  • Zabielski, P.
  • Zídková, J.
  • Škop, V.
  • Ždychová, Jana
issn
  • 0862-8408
number of pages
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