The Increased Activity of Liver Lysosomal Lipase in Nonalcoholic Fatty Liver Disease Contributes to the Development of Hepatic Insulin Resistance
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 L...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Biochemistry Research International |
| Online Access: | http://dx.doi.org/10.1155/2012/135723 |
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| author | Monika Cahova Helena Dankova Eliska Palenickova Zuzana Papackova Radko Komers Jana Zdychova Eva Sticova Ludmila Kazdova |
| author_facet | Monika Cahova Helena Dankova Eliska Palenickova Zuzana Papackova Radko Komers Jana Zdychova Eva Sticova Ludmila Kazdova |
| author_sort | Monika Cahova |
| collection | DOAJ |
| description | 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 PKCε 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 PKCε activation. |
| format | Article |
| id | doaj-art-7ed24344729042418f9f135362730f23 |
| institution | Kabale University |
| issn | 2090-2247 2090-2255 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Biochemistry Research International |
| spelling | doaj-art-7ed24344729042418f9f135362730f232025-02-03T01:31:38ZengWileyBiochemistry Research International2090-22472090-22552012-01-01201210.1155/2012/135723135723The Increased Activity of Liver Lysosomal Lipase in Nonalcoholic Fatty Liver Disease Contributes to the Development of Hepatic Insulin ResistanceMonika Cahova0Helena Dankova1Eliska Palenickova2Zuzana Papackova3Radko Komers4Jana Zdychova5Eva Sticova6Ludmila Kazdova7Department of Metabolism and Diabetes, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 14021 Prague 4, Czech RepublicDepartment of Metabolism and Diabetes, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 14021 Prague 4, Czech RepublicDepartment of Metabolism and Diabetes, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 14021 Prague 4, Czech RepublicDepartment of Metabolism and Diabetes, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 14021 Prague 4, Czech RepublicDiabetes Center, Institute for Clinical and Experimental Medicine, 14021 Prague 4, Czech RepublicDiabetes Center, Institute for Clinical and Experimental Medicine, 14021 Prague 4, Czech RepublicLaboratory of Experimental Hepatology, Institute for Clinical and Experimental Medicine, 14021 Prague 4, Czech RepublicDepartment of Metabolism and Diabetes, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 14021 Prague 4, Czech RepublicWe 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 PKCε 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 PKCε activation.http://dx.doi.org/10.1155/2012/135723 |
| spellingShingle | Monika Cahova Helena Dankova Eliska Palenickova Zuzana Papackova Radko Komers Jana Zdychova Eva Sticova Ludmila Kazdova The Increased Activity of Liver Lysosomal Lipase in Nonalcoholic Fatty Liver Disease Contributes to the Development of Hepatic Insulin Resistance Biochemistry Research International |
| title | The Increased Activity of Liver Lysosomal Lipase in Nonalcoholic Fatty Liver Disease Contributes to the Development of Hepatic Insulin Resistance |
| title_full | The Increased Activity of Liver Lysosomal Lipase in Nonalcoholic Fatty Liver Disease Contributes to the Development of Hepatic Insulin Resistance |
| title_fullStr | The Increased Activity of Liver Lysosomal Lipase in Nonalcoholic Fatty Liver Disease Contributes to the Development of Hepatic Insulin Resistance |
| title_full_unstemmed | The Increased Activity of Liver Lysosomal Lipase in Nonalcoholic Fatty Liver Disease Contributes to the Development of Hepatic Insulin Resistance |
| title_short | The Increased Activity of Liver Lysosomal Lipase in Nonalcoholic Fatty Liver Disease Contributes to the Development of Hepatic Insulin Resistance |
| title_sort | increased activity of liver lysosomal lipase in nonalcoholic fatty liver disease contributes to the development of hepatic insulin resistance |
| url | http://dx.doi.org/10.1155/2012/135723 |
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