Autophagy-Lysosomal Pathway Is Involved in Lipid Degradation in Rat Liver

Skop,; Cahová, Monika; Papáčková, Zuzana; Páleníčková, Eliška; Daňková, Helena; Baranowski, Marcin; Zabielski, Piotr; Ždychová, Jana; Zídková, J.; Kazdová, Ludmila

doi:10.33549/physiolres.932285

Cited by 55 publications

(28 citation statements)

References 27 publications

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“…Microtubule-associated protein light chain 3 (LC3), a mammalian homologue of yeast Apg8p, was used as a marker of autophagy induction, because cytosolic LC3-I is processed to its lipidated LC3-II form upon autophagy induction [ 38 ]. LC3 is initially synthesized in an unprocessed form, pro-LC3, which is converted into the proteolytically processed form LC3-I, lacking amino acids from the C-terminus, and is finally modified into a phosphatidylethanolamine-conjugated form LC3-II [ 39 ]. LC3-II is the protein marker that is reliably associated with phagosomes, sealed autophagosomes, and mature autophagosomes/lysosomes [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Jujuboside A Protects H9C2 Cells from Isoproterenol-Induced Injury via Activating PI3K/Akt/mTOR Signaling Pathway

Han

Wan

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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Jujuboside A is a kind of the saponins isolated from the seeds of Ziziphus jujuba, which possesses multiple biological effects, such as antianxiety, antioxidant, and anti-inflammatory effects; however, its mediatory effect on isoproterenol-stimulated cardiomyocytes has not been investigated yet. In this study, we tried to detect the protective effect and potential mechanism of JUA on ISO-induced cardiomyocytes injury. H9C2 cells were treated with ISO to induce cell damage. Cells were pretreated with JUA to investigate the effects on the cell viability, morphological changes, light chain 3 conversion, and the activation of PI3K/Akt/mTOR signaling pathway. Results showed that ISO significantly inhibited the cell viability in a time- and dose-dependent manner. JUA pretreatment could reverse the reduction of cell viability and better the injury of H9C2 cells induced by ISO. Western blot analysis showed that JUA could accelerate the phosphorylation of PI3K, Akt, and mTOR. Results also indicated that JUA could significantly decrease the ratio of microtubule-associated protein LC3-II/I in H9C2 cells. Taken together, our research showed that JUA could notably reduce the damage cause by ISO via promoting the phosphorylation of PI3K, Akt, and mTOR and inhibiting LC3 conversion, which may be a potential choice for the treatment of heart diseases.

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Section: Discussionmentioning

confidence: 99%

Jujuboside A Protects H9C2 Cells from Isoproterenol-Induced Injury via Activating PI3K/Akt/mTOR Signaling Pathway

Han

Wan

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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“…Previous studies have implicated a role of autophagy in hepatic lipid metabolism. Škop et al ( 26 ) suggested that the inhibition of the autophagic flux or lysosomal activity decreased the secretion of very low density lipoprotein and formation of FFA oxidative products, while the stimulation of autophagy by RAPA increased some of these indicators. The study by Singh et al ( 13 ) demonstrated that the inhibition of autophagy (by pharmacological or genetic approaches) in cultured hepatocytes and mouse liver increased TG storage in lipid droplets.…”

Section: Discussionmentioning

confidence: 99%

Liraglutide reduces lipid accumulation in steatotic L-02 cells by enhancing autophagy

Zhou

Zhang

Zhu

2014

Molecular Medicine Reports

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Simple hepatic steatosis is the early stage of non-alcoholic fatty liver disease and is recognized as a benign process. Previous studies show that glucagon-like peptide-1 has great potential in improving hepatic steatosis. Recent data have revealed that inhibiting autophagy exacerbates lipid accumulation in hepatocytes. Therefore, the present study aimed to determine the effects of liraglutide (LG) on simple hepatic steatosis and the possible role of autophagy. Firstly, steatotic L-02 cells were induced by incubating L-02 cells with 1 mmol/l free fatty acid (FFA) mixture (oleic acid and palmitic acid at a molar ratio of 2:1) for 24 h. Intracellular lipid accumulation, cell viability, oxidative stress and apoptosis were evaluated. Secondly, steatotic L-02 cells were treated with 10 or 100 nmol/l LG, 100 nmol/l LG plus 3-methyladenine (3-MA), or rapamycin for 24 h, and then lipid accumulation was measured. Next, the degree of lipid accumulation and the intensity of autophagy were assessed. Oil red O staining and triglyceride quantification demonstrated notable steatosis in L-02 cells following exposure to 1 mmol/l FFA mixture for 24 h. There was no significant cytotoxicity, oxidative stress or apoptosis in steatotic L-02 cells. Treatment with 100 nmol/l LG reduced lipid accumulation in steatotic L-02 cells and increased the mRNA levels of microtubule-associated protein 1 light chain 3B. Additionally, it enhanced the autophagic flux in steatotic L-02 cells, as measured by western blot analysis and shown by electron microscopy. Additionally, 3-MA weakened the ability of LG to improve hepatic steatosis and enhance autophagy. Our data indicate that LG reduces the lipid accumulation in steatotic L-02 cells, and the activation of autophagy plays a significant role in this process.

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“…In this study, we focused on a recently discovered nonclassical pathway of lypolysis: the autophagy-lysosomal pathway. [12][13][14] The autophagic process involves sequestration of cytoplasmic contents in double-membrane autophagosomes (a process that embodies lipidation of microtubuleassociated protein light-chain 3 [LC3]), followed by fusion with lysosomes to form autolysosomes, and subsequent degradation of the cytosolic components by acid proteases, hydrolases, and lipases within the autolysosomes. 15 Our results show that caffeine increases lipid droplet turnover, fat oxidation, and oxidative phosphorylation in hepatic cells by the autophagy-mediated pathway.…”

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confidence: 99%

Caffeine stimulates hepatic lipid metabolism by the autophagy-lysosomal pathway in mice

et al. 2014

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Caffeine is one of the world's most consumed drugs. Recently, several studies showed that its consumption is associated with lower risk for nonalcoholic fatty liver disease (NAFLD), an obesity-related condition that recently has become the major cause of liver disease worldwide. Although caffeine is known to stimulate hepatic fat oxidation, its mechanism of action on lipid metabolism is still not clear. Here, we show that caffeine surprisingly is a potent stimulator of hepatic autophagic flux. Using genetic, pharmacological, and metabolomic approaches, we demonstrate that caffeine reduces intrahepatic lipid content and stimulates b-oxidation in hepatic cells and liver by an autophagy-lysosomal pathway. Furthermore, caffeine-induced autophagy involved down-regulation of mammalian target of rapamycin signaling and alteration in hepatic amino acids and sphingolipid levels. In mice fed a high-fat diet, caffeine markedly reduces hepatosteatosis and concomitantly increases autophagy and lipid uptake in lysosomes. Conclusion: These results provide novel insight into caffeine's lipolytic actions through autophagy in mammalian liver and its potential beneficial effects in NAFLD. (HEPATOLOGY 2014;59:1366-1380 See Editorial on Page 1235 C affeine is one of the most widely consumed drugs in the world. Although its effect on whole-body metabolism and fat oxidation has been well documented in both animals and humans, [1][2][3] little is known about its direct action on the liver.The liver is the major site for fatty acid oxidation (FAO) in mammals. Decreased turnover of hepatic lipid droplets can lead to the development of fatty liver disease in humans. 4 Recently, the rapid rise in the prevalence of obesity and diabetes in the general population has contributed to a parallel increase in nonalcoholic fatty liver disease (NAFLD) in many parts of the world. Currently, it is estimated that up to 46% of the adult U.S. population may have hepatosteatosis. 5 Presently, there are no effective drug therapies for NAFLD, currently considered a risk factor for type II diabetes. 6 Recently, several studies have shown that caffeine intake in humans and animals is inversely correlated with severity of NAFLD and type II diabetes, 7-11 but the mechanism for this action is not known.

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Autophagy-Lysosomal Pathway Is Involved in Lipid Degradation in Rat Liver

Cited by 55 publications

References 27 publications

Jujuboside A Protects H9C2 Cells from Isoproterenol-Induced Injury via Activating PI3K/Akt/mTOR Signaling Pathway

Jujuboside A Protects H9C2 Cells from Isoproterenol-Induced Injury via Activating PI3K/Akt/mTOR Signaling Pathway

Liraglutide reduces lipid accumulation in steatotic L-02 cells by enhancing autophagy

Caffeine stimulates hepatic lipid metabolism by the autophagy-lysosomal pathway in mice

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