Reduced Brain Content of Arachidonic Acid and Docosahexaenoic Acid Is Related to the Severity of Liver Fibrosis

Chen, Chih‐Cheng; Huang, Laura; Tain, You‐Lin; Chaung, Hsio-Chi; Hsieh, Chih-Sung; Eng, Hock‐Liew; Wei, Yu‐Ching; Yang, Changzheng

doi:10.1007/s10620-009-1120-x

Cited by 8 publications

(5 citation statements)

References 27 publications

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“…It has been proposed that the nervous system is associated with hepatic glucose and lipid metabolism, 25 emphasizing the importance of the brain-liver axis in organ-organ communication. Moreover, the reduced levels of arachidonic acid and docosahexaenoic acid in the brain were closely linked to hepatic fibrosis 26 . On the other hand, liver fibrosis patients were confirmed to behave impaired cognitive issues 27 .…”

Section: Discussionmentioning

confidence: 98%

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Tyrosine kinase receptor B attenuates liver fibrosis by inhibiting TGF-β/SMAD signaling

Song

Wei

et al. 2023

Hepatology

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Background and Aims: Liver fibrosis is a leading indicator for increased mortality and long-term comorbidity in NASH. Activation of HSCs and excessive extracellular matrix production are the hallmarks of liver fibrogenesis. Tyrosine kinase receptor (TrkB) is a multifunctional receptor that participates in neurodegenerative disorders. However, paucity of literature is available about TrkB function in liver fibrosis. Herein, the regulatory network and therapeutic potential of TrkB were explored in the progression of hepatic fibrosis. Methods and Results: The protein level of TrkB was decreased in mouse models of CDAHFD feeding or carbon tetrachloride-induced hepatic fibrosis. TrkB suppressed TGF-β-stimulated proliferation and activation of HSCs in 3-dimensional liver spheroids and significantly repressed TGF-β/SMAD signaling pathway either in HSCs or in hepatocytes. The cytokine, TGF-β, boosted Nedd4 family interacting protein-1 (Ndfip1) expression, promoting the ubiquitination and degradation of TrkB through E3 ligase Nedd4-2. Moreover, carbon tetrachloride intoxication-induced hepatic fibrosis in mouse models was reduced by adeno-associated virus vector serotype 6 (AAV6)–mediated TrkB overexpression in HSCs. In addition, in murine models of CDAHFD feeding and Gubra-Amylin NASH (GAN), fibrogenesis was reduced by adeno-associated virus vector serotype 8 (AAV8)–mediated TrkB overexpression in hepatocytes. Conclusion: TGF-β stimulated TrkB degradation through E3 ligase Nedd4-2 in HSCs. TrkB overexpression inhibited the activation of TGF-β/SMAD signaling and alleviated the hepatic fibrosis both in vitro and in vivo. These findings demonstrate that TrkB could be a significant suppressor of hepatic fibrosis and confer a potential therapeutic target in hepatic fibrosis.

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Section: Discussionmentioning

confidence: 98%

“…Moreover, the reduced levels of arachidonic acid and docosahexaenoic acid in the brain were closely linked to hepatic fibrosis. 26 On the other hand, liver fibrosis patients were confirmed to behave impaired cognitive issues. 27 Thus, brain-liver relationships were considered to play a role in the progression of hepatic fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Tyrosine kinase receptor B attenuates liver fibrosis by inhibiting TGF-β/SMAD signaling

Song

Wei

et al. 2023

Hepatology

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“…Chen et al found that concentrations of 20:4 n‐6 and 22:6 n‐3 fatty acyls were reduced in the brain of BDL rats 2–4 weeks after surgery. These results had an inverse correlation with the duration of bile duct ligation, severity of liver fibrosis, and plasma bilirubin (Chen et al, 2010). Using a more comprehensive lipidomics approach, our findings suggest that the total amount of lipids in the cerebellum was reduced in the BDL group which was mainly driven by reductions in the phospholipid classes PI, PS, and PC O‐.…”

Section: Discussionmentioning

confidence: 99%

Cholestasis alters brain lipid and bile acid composition and compromises motor function in neonatal piglets

Henriksen

Hansen

Lycas

et al. 2022

Physiological Reports

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“…showed that an omega-3 fatty acid isolated from fish oil, DHA, inhibited hepatic inflammation by targeting both TLR4 and TLR9 [81]. In fact, DHA is currently in phase II of clinical trials in the United States for liver fibrosis treatment [82]. These reports demonstrate that natural products can serve as potential drug candidates for inflammatory conditions such as sepsis and autoimmune disorders.…”

Section: Tlr Dysregulationmentioning

confidence: 99%

Modulation of Toll-like receptor signaling in innate immunity by natural products

Chen

2016

International Immunopharmacology

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For centuries, natural products and their derivatives have provided a rich source of compounds for the development of new immunotherapies in the treatment of human disease. Many of these compounds are currently undergoing clinical trials, particularly as anti-oxidative, anti-microbial, and anti-cancer agents. However, the function and mechanism of natural products in how they interact with our immune system has yet to be extensively explored. Natural immune modulators may provide the key to control and ultimately defeat disorders affecting the immune system. They can either up- or down-regulate the immune response with few adverse side effects. In this review, we summarize the recent advancements made in utilizing natural products for immunomodulation and their important molecular targets, members of the Toll-like receptor (TLR) family, in the innate immune system.

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Reduced Brain Content of Arachidonic Acid and Docosahexaenoic Acid Is Related to the Severity of Liver Fibrosis

Abstract: Our results demonstrated that reduced AA and DHA content in the brain of rats which received bile duct ligation is closely related to both the severity of liver fibrosis and the impairment of liver function.

Cited by 8 publications

References 27 publications

Tyrosine kinase receptor B attenuates liver fibrosis by inhibiting TGF-β/SMAD signaling

Tyrosine kinase receptor B attenuates liver fibrosis by inhibiting TGF-β/SMAD signaling

Cholestasis alters brain lipid and bile acid composition and compromises motor function in neonatal piglets

Modulation of Toll-like receptor signaling in innate immunity by natural products

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