The increased activity of liver lysosomal lipase in nonalcoholic fatty liver disease contributes to the development of hepatic insulin resistance

Monika Cahova, Helena Dankova, Eliska Palenickova, Zuzana Papackova, Radko Komers, Jana Zdychova, Eva Sticova, Ludmila Kazdova

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We tested the hypothesis that TAG accumulation in the liver induced by short-term high-fat diet (HFD) in rats leads to the dysregulation of endogenous TAG degradation by lysosomal lipase (LIPA) via lysosomal pathway and is causally linked with the onset of hepatic insulin resistance. We found that LIPA could be translocated between qualitatively different depots (light and dense lysosomes). In contrast to dense lysosomal fraction, LIPA associated with light lysosomes exhibits high activity on both intracellular TAG and exogenous substrate and prandial- or diet-dependent regulation. On standard diet, LIPA activity was upregulated in fasted and downregulated in fed animals. In the HFD group, we demonstrated an increased TAG content, elevated LIPA activity, enhanced production of diacylglycerol, and the abolishment of prandial-dependent LIPA regulation in light lysosomal fraction. The impairment of insulin signalling and increased activation of PKC was found in liver of HFD-fed animals. Lipolysis of intracellular TAG, mediated by LIPA, is increased in steatosis probably due to the enhanced formation of phagolysosomes. Consequent overproduction of diacylglycerol may represent the causal link between HFD-induced hepatic TAG accumulation and hepatic insulin resistance via PKC activation.

Original languageEnglish (US)
Article number135723
JournalBiochemistry Research International
DOIs
StatePublished - 2012

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Lipase
Liver
Nutrition
Insulin Resistance
Insulin
High Fat Diet
Fats
Diglycerides
Lysosomes
Meals
Animals
Chemical activation
Diet
Light
Phagosomes
Lipolysis
Non-alcoholic Fatty Liver Disease
Rats
Down-Regulation
Degradation

ASJC Scopus subject areas

  • Biochemistry

Cite this

The increased activity of liver lysosomal lipase in nonalcoholic fatty liver disease contributes to the development of hepatic insulin resistance. / Cahova, Monika; Dankova, Helena; Palenickova, Eliska; Papackova, Zuzana; Komers, Radko; Zdychova, Jana; Sticova, Eva; Kazdova, Ludmila.

In: Biochemistry Research International, 2012.

Research output: Contribution to journalArticle

Cahova, Monika ; Dankova, Helena ; Palenickova, Eliska ; Papackova, Zuzana ; Komers, Radko ; Zdychova, Jana ; Sticova, Eva ; Kazdova, Ludmila. / The increased activity of liver lysosomal lipase in nonalcoholic fatty liver disease contributes to the development of hepatic insulin resistance. In: Biochemistry Research International. 2012.
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AU - Cahova, Monika

AU - Dankova, Helena

AU - Palenickova, Eliska

AU - Papackova, Zuzana

AU - Komers, Radko

AU - Zdychova, Jana

AU - Sticova, Eva

AU - Kazdova, Ludmila

PY - 2012

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