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FXR-mediated inhibition of autophagy contributes to FA-induced TG accumulation and accordingly reduces FA-induced lipotoxicity

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FXR-mediated inhibition of autophagy contributes to FA-induced TG accumulation and accordingly reduces FA-induced lipotoxicity. / Wu, Kun; Zhao, Tao; Hogstrand, Christer; Xu, Yi-Chuang; Ling, Shi-Cheng; Chen, Guang-Hui; Luo, Zhi.

In: Cell communication and signaling : CCS, Vol. 18, No. 47, 47, 20.03.2020.

Research output: Contribution to journalArticle

Harvard

Wu, K, Zhao, T, Hogstrand, C, Xu, Y-C, Ling, S-C, Chen, G-H & Luo, Z 2020, 'FXR-mediated inhibition of autophagy contributes to FA-induced TG accumulation and accordingly reduces FA-induced lipotoxicity', Cell communication and signaling : CCS, vol. 18, no. 47, 47. https://doi.org/10.1186/s12964-020-0525-1

APA

Wu, K., Zhao, T., Hogstrand, C., Xu, Y-C., Ling, S-C., Chen, G-H., & Luo, Z. (2020). FXR-mediated inhibition of autophagy contributes to FA-induced TG accumulation and accordingly reduces FA-induced lipotoxicity. Cell communication and signaling : CCS, 18(47), [47]. https://doi.org/10.1186/s12964-020-0525-1

Vancouver

Wu K, Zhao T, Hogstrand C, Xu Y-C, Ling S-C, Chen G-H et al. FXR-mediated inhibition of autophagy contributes to FA-induced TG accumulation and accordingly reduces FA-induced lipotoxicity. Cell communication and signaling : CCS. 2020 Mar 20;18(47). 47. https://doi.org/10.1186/s12964-020-0525-1

Author

Wu, Kun ; Zhao, Tao ; Hogstrand, Christer ; Xu, Yi-Chuang ; Ling, Shi-Cheng ; Chen, Guang-Hui ; Luo, Zhi. / FXR-mediated inhibition of autophagy contributes to FA-induced TG accumulation and accordingly reduces FA-induced lipotoxicity. In: Cell communication and signaling : CCS. 2020 ; Vol. 18, No. 47.

Bibtex Download

@article{460f9d5de71f4df2b129e09cb4261ec5,
title = "FXR-mediated inhibition of autophagy contributes to FA-induced TG accumulation and accordingly reduces FA-induced lipotoxicity",
abstract = "Background: Excessive dietary fat intake induces lipid deposition and contributes to the progress of nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanisms are still unclear. Methods: Yellow catfish were given two experimental diets with dietary lipid levels of 11.3 and 15.4{\%}, respectively, for 56 days, and the contents of triglyceride (TG), nonesterified free fatty acids (NEFA) and bile acid (BA), RNA-seq, enzymatic activities and mRNA expression were deteremined in the liver tissues. Hepatocytes from yellow catfish liver tissues were isolated and cultured. Fatty acids (FA) (palmitic acid: OA, oleic acid =1:1), pathway inhibitors (MA, autophagy inhibitor; guggulsterone, FXR inhibitor) and agonist (rapamyicn, autophagy agonist; GW4064, FXR agonist) were used to incubate the cells. TG and NEFA contents, ultrastructural observation, autophagic vesicles and intracellular LD,apoptosis,western blot and Co-IP, and Immunofluorescence analysis, enzymatic activities and Q-PCR were decided. Results: Using RNA sequencing, we found that high fat diets induced changes in expression of many genes associated with the pathways of lipid metabolism and autophagy. The mRNA profiles of the differentially expressed genes (DEG) indicated that high dietary fat-induced lipid deposition was predominantly influenced by the inhibition of autophagy. Using primary hepatocytes, we found that fatty acids (FA) suppressed autophagy, which in turn reduced cellular free FA level by decreasing triglyceride (TG) breakdown. Moreover, our study indicated that farnesoid X receptor (FXR)-cyclic AMP-responsive element-binding protein (CREB) axis was the pivotal physiological switch regulating FA-induced changes of autophagy and lipid metabolism, which represented cellular defenses against FA-induced lipotoxicity. Conclusion: This discovery may provide new targets for treating pathological changes involved in the dysfunction of autophagy and metabolism, including NAFLD. [MediaObject not available: see fulltext.] Graphical abstract: [Figure not available: see fulltext.]",
keywords = "Autophagy, FXR, Lipid metabolism, Lipotoxicity, RNA-seq transcriptome",
author = "Kun Wu and Tao Zhao and Christer Hogstrand and Yi-Chuang Xu and Shi-Cheng Ling and Guang-Hui Chen and Zhi Luo",
year = "2020",
month = "3",
day = "20",
doi = "10.1186/s12964-020-0525-1",
language = "English",
volume = "18",
journal = "Cell communication and signaling : CCS",
issn = "1478-811X",
publisher = "Signal Transduction Society",
number = "47",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - FXR-mediated inhibition of autophagy contributes to FA-induced TG accumulation and accordingly reduces FA-induced lipotoxicity

AU - Wu, Kun

AU - Zhao, Tao

AU - Hogstrand, Christer

AU - Xu, Yi-Chuang

AU - Ling, Shi-Cheng

AU - Chen, Guang-Hui

AU - Luo, Zhi

PY - 2020/3/20

Y1 - 2020/3/20

N2 - Background: Excessive dietary fat intake induces lipid deposition and contributes to the progress of nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanisms are still unclear. Methods: Yellow catfish were given two experimental diets with dietary lipid levels of 11.3 and 15.4%, respectively, for 56 days, and the contents of triglyceride (TG), nonesterified free fatty acids (NEFA) and bile acid (BA), RNA-seq, enzymatic activities and mRNA expression were deteremined in the liver tissues. Hepatocytes from yellow catfish liver tissues were isolated and cultured. Fatty acids (FA) (palmitic acid: OA, oleic acid =1:1), pathway inhibitors (MA, autophagy inhibitor; guggulsterone, FXR inhibitor) and agonist (rapamyicn, autophagy agonist; GW4064, FXR agonist) were used to incubate the cells. TG and NEFA contents, ultrastructural observation, autophagic vesicles and intracellular LD,apoptosis,western blot and Co-IP, and Immunofluorescence analysis, enzymatic activities and Q-PCR were decided. Results: Using RNA sequencing, we found that high fat diets induced changes in expression of many genes associated with the pathways of lipid metabolism and autophagy. The mRNA profiles of the differentially expressed genes (DEG) indicated that high dietary fat-induced lipid deposition was predominantly influenced by the inhibition of autophagy. Using primary hepatocytes, we found that fatty acids (FA) suppressed autophagy, which in turn reduced cellular free FA level by decreasing triglyceride (TG) breakdown. Moreover, our study indicated that farnesoid X receptor (FXR)-cyclic AMP-responsive element-binding protein (CREB) axis was the pivotal physiological switch regulating FA-induced changes of autophagy and lipid metabolism, which represented cellular defenses against FA-induced lipotoxicity. Conclusion: This discovery may provide new targets for treating pathological changes involved in the dysfunction of autophagy and metabolism, including NAFLD. [MediaObject not available: see fulltext.] Graphical abstract: [Figure not available: see fulltext.]

AB - Background: Excessive dietary fat intake induces lipid deposition and contributes to the progress of nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanisms are still unclear. Methods: Yellow catfish were given two experimental diets with dietary lipid levels of 11.3 and 15.4%, respectively, for 56 days, and the contents of triglyceride (TG), nonesterified free fatty acids (NEFA) and bile acid (BA), RNA-seq, enzymatic activities and mRNA expression were deteremined in the liver tissues. Hepatocytes from yellow catfish liver tissues were isolated and cultured. Fatty acids (FA) (palmitic acid: OA, oleic acid =1:1), pathway inhibitors (MA, autophagy inhibitor; guggulsterone, FXR inhibitor) and agonist (rapamyicn, autophagy agonist; GW4064, FXR agonist) were used to incubate the cells. TG and NEFA contents, ultrastructural observation, autophagic vesicles and intracellular LD,apoptosis,western blot and Co-IP, and Immunofluorescence analysis, enzymatic activities and Q-PCR were decided. Results: Using RNA sequencing, we found that high fat diets induced changes in expression of many genes associated with the pathways of lipid metabolism and autophagy. The mRNA profiles of the differentially expressed genes (DEG) indicated that high dietary fat-induced lipid deposition was predominantly influenced by the inhibition of autophagy. Using primary hepatocytes, we found that fatty acids (FA) suppressed autophagy, which in turn reduced cellular free FA level by decreasing triglyceride (TG) breakdown. Moreover, our study indicated that farnesoid X receptor (FXR)-cyclic AMP-responsive element-binding protein (CREB) axis was the pivotal physiological switch regulating FA-induced changes of autophagy and lipid metabolism, which represented cellular defenses against FA-induced lipotoxicity. Conclusion: This discovery may provide new targets for treating pathological changes involved in the dysfunction of autophagy and metabolism, including NAFLD. [MediaObject not available: see fulltext.] Graphical abstract: [Figure not available: see fulltext.]

KW - Autophagy

KW - FXR

KW - Lipid metabolism

KW - Lipotoxicity

KW - RNA-seq transcriptome

UR - http://www.scopus.com/inward/record.url?scp=85082073014&partnerID=8YFLogxK

U2 - 10.1186/s12964-020-0525-1

DO - 10.1186/s12964-020-0525-1

M3 - Article

VL - 18

JO - Cell communication and signaling : CCS

JF - Cell communication and signaling : CCS

SN - 1478-811X

IS - 47

M1 - 47

ER -

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