Spontaneous nonalcoholic fatty liver disease and ER stress in Sidt2 deficiency mice

Gao, Jialin; Zhang, Yao; Yu, Changhong; Tan, Fengbiao; Wang, Lizhuo

doi:10.1016/j.bbrc.2016.05.122

Cited by 33 publications

(35 citation statements)

References 18 publications

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“…These investigators identified mouse SIDT2 function in lipid metabolism. SIDT2-deficient mice have increased serum triglyceride [ 32 ]. TAGLN (Transgelin, sm22α) is an actin-binding protein expressed in smooth muscle cells [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Multiple genotype–phenotype association study reveals intronic variant pair on SIDT2 associated with metabolic syndrome in a Korean population

et al. 2018

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BackgroundMetabolic syndrome is a risk factor for type 2 diabetes and cardiovascular disease. We identified common genetic variants that alter the risk for metabolic syndrome in the Korean population. To isolate these variants, we conducted a multiple-genotype and multiple-phenotype genome-wide association analysis using the family-based quasi-likelihood score (MFQLS) test. For this analysis, we used 7211 and 2838 genotyped study subjects for discovery and replication, respectively. We also performed a multiple-genotype and multiple-phenotype analysis of a gene-based single-nucleotide polymorphism (SNP) set.ResultsWe found an association between metabolic syndrome and an intronic SNP pair, rs7107152 and rs1242229, in SIDT2 gene at 11q23.3. Both SNPs correlate with the expression of SIDT2 and TAGLN, whose products promote insulin secretion and lipid metabolism, respectively. This SNP pair showed statistical significance at the replication stage.ConclusionsOur findings provide insight into an underlying mechanism that contributes to metabolic syndrome.Electronic supplementary materialThe online version of this article (10.1186/s40246-018-0180-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Multiple genotype–phenotype association study reveals intronic variant pair on SIDT2 associated with metabolic syndrome in a Korean population

et al. 2018

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“…However, this same study reported an accumulation of RNA in lysosomes and that the function of SIDT2 is to export RNA from lysosomes into the cytosol 121 . Additionally, several studies characterizing SIDT2-knockout mice have reported defects in insulin secretion 123,124 , hepatic lipid metabolism 125,126 and autophagic flux 127 , which do not seem to involve nucleic acid degradation but should be investigated to clarify the physiological role of RDA.…”

Section: Rn/dnautophagymentioning

confidence: 99%

Lysosome biology in autophagy

2020

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Autophagy is a major intracellular degradation system that derives its degradative abilities from the lysosome. The most well-studied form of autophagy is macroautophagy, which delivers cytoplasmic material to lysosomes via the double-membraned autophagosome. Other forms of autophagy, namely chaperone-mediated autophagy and microautophagy, occur directly on the lysosome. Besides providing the means for degradation, lysosomes are also involved in autophagy regulation and can become substrates of autophagy when damaged. During autophagy, they exhibit notable changes, including increased acidification, enhanced enzymatic activity, and perinuclear localization. Despite their importance to autophagy, details on autophagy-specific regulation of lysosomes remain relatively scarce. This review aims to provide a summary of current understanding on the behaviour of lysosomes during autophagy and outline unexplored areas of autophagy-specific lysosome research.

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“…Studies reveal that a large amount of lipid deposition is observed in the cell model of NAFLD, and the levels of TG are elevated [26,27]. Besides, when lipid accumulation in the liver cells of NAFLD mice is increased, the TG content in liver tissue is also increased [28]. Consistent with previous studies, we found that the miR-499-5p inhibitor was also found to be clearly reduced the TG content of the NAFLD models, suggesting that miR-499-5p might improve the fatty degeneration of NAFLD hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of miR-499-5p expression improves nonalcoholic fatty liver disease

Liu

Wang

Chen

et al. 2019

Preprint

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Background: Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases. However, the pathogenesis of NAFLD is largely unknown. Here, we investigated the specific role of miR-499-5p in NAFLD. Method: Free fatty acid (FFA) was used to induce HL-7702 cell line to establish a NAFLD cell model, and animal models of NAFLD were constructed by feeding C57BL/6 mice with high fat diet (HFD). Expression levels of miR-499-5p in the HL-7702 cells and C57BL/6 mice were determined by RT-qPCR. In addition, functional experiments were carried out through transfecting miR-499-5p inhibitor into NAFLD cells, and injecting NAFLD mice with a lentiviral vector with knock down the miR-499-5p . Furthermore, the effects of miR-499-5p inhibition on lipidation and inflammation were investigated by oil red O staining, HE staining, and biochemical analysis. Results: Compared with normal controls, the expression of miR-499-5p was significantly up-regulated in NAFLD cells and tissues in mouse (P < 0.05). After NAFLD cells transfected by miR-499-5p inhibitor, the expression of miR-499-5p was inhibited, the lipid deposition and content of TG were reduced, and the lipidation was improved (P < 0.05). Simultaneously, after NAFLD mice were injected with knocked down the miR-499-5p lentiviral vector, the degree of lipid droplet deposition and content of TG were also reduced. Besides, it also decreased the levels of TC and AST in serum, and improved hepatic lipid metabolism (P < 0.05). Conclusion: Inhibition of miR-499-5p expression improved NAFLD in mice, which provided a new direction for the treatment of NAFLD.

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Spontaneous nonalcoholic fatty liver disease and ER stress in Sidt2 deficiency mice

Cited by 33 publications

References 18 publications

Multiple genotype–phenotype association study reveals intronic variant pair on SIDT2 associated with metabolic syndrome in a Korean population

Multiple genotype–phenotype association study reveals intronic variant pair on SIDT2 associated with metabolic syndrome in a Korean population

Lysosome biology in autophagy

Inhibition of miR-499-5p expression improves nonalcoholic fatty liver disease

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