Ciliary neurotrophic factor analogue aggravates CCl4-induced acute hepatic injury in rats

Ciliary neurotrophic factor (CNTF) and CNTF analogs were reported to have hepatoprotective effect and ameliorate hepatic steatosis in db/db or high-fat-diet-fed mice. Because hepatic steatosis and injury are also commonly induced by hepatotoxin, the aim of the present study is to clarify whether CNTF could alleviate hepatic steatosis and injury induced by carbon tetrachloride (CCl4). Unexpectedly, when combined with CCl4, CNTF aggravated hepatic steatosis and liver injury. The mechanism is associated with effects of CNTF that inhibited lipoprotein secretion and drastically impaired the ability of lipoproteins to act as transport vehicles for lipids from the liver to the circulation. While injected after CCl4 cessation, CNTF could improve liver function. These data suggest that CNTF could be a potential hepatoprotective agent against CCl4-induced hepatic injury after the cessation of CCl4 exposure. However, it is forbidden to combine recombinant mutant of human CNTF treatment with CCl4.

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Opposite effects of a high-fat diet and calorie restriction on ciliary neurotrophic factor signaling in the mouse hypothalamus

Frontiers in Neuroscience ◽

10.3389/fnins.2013.00263 ◽

2013 ◽

Vol 7 ◽

Cited By ~ 15

Author(s):

Ilenia Severi ◽

Jessica Perugini ◽

Eleonora Mondini ◽

Arianna Smorlesi ◽

Andrea Frontini ◽

...

Keyword(s):

Calorie Restriction ◽

Neurotrophic Factor ◽

High Fat Diet ◽

Ciliary Neurotrophic Factor ◽

High Fat ◽

Neurotrophic Factor Signaling

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Alleviative effect of ciliary neurotrophic factor analogue on high fat-induced hepatic steatosis is partially independent of the central regulation

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/1440-1681.12709 ◽

2017 ◽

Vol 44 (3) ◽

pp. 395-402 ◽

Cited By ~ 2

Author(s):

Ming-Xia Cui ◽

Li-Ning Yang ◽

Xiao-Xia Wang ◽

Lei Wang ◽

Rui-Lian Li ◽

...

Keyword(s):

Hepatic Steatosis ◽

Neurotrophic Factor ◽

Ciliary Neurotrophic Factor ◽

Central Regulation ◽

High Fat

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Glial cell line-derived neurotrophic factor protects against high-fat diet-induced hepatic steatosis by suppressing hepatic PPAR-γ expression

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00196.2015 ◽

2016 ◽

Vol 310 (2) ◽

pp. G103-G116 ◽

Cited By ~ 4

Author(s):

Simon Musyoka Mwangi ◽

Sophia Peng ◽

Behtash Ghazi Nezami ◽

Natalie Thorn ◽

Alton B. Farris ◽

...

Keyword(s):

Cell Line ◽

Hepatic Steatosis ◽

Glial Cell ◽

Neurotrophic Factor ◽

High Fat Diet ◽

De Novo ◽

De Novo Lipogenesis ◽

High Fat ◽

Protein Levels ◽

Ppar Γ

Glial cell line-derived neurotrophic factor (GDNF) protects against high-fat diet (HFD)-induced hepatic steatosis in mice, however, the mechanisms involved are not known. In this study we investigated the effects of GDNF overexpression and nanoparticle delivery of GDNF in mice on hepatic steatosis and fibrosis and the expression of genes involved in the regulation of hepatic lipid uptake and de novo lipogenesis. Transgenic overexpression of GDNF in liver and other metabolically active tissues was protective against HFD-induced hepatic steatosis. Mice overexpressing GDNF had significantly reduced P62/sequestosome 1 protein levels suggestive of accelerated autophagic clearance. They also had significantly reduced peroxisome proliferator-activated receptor-γ (PPAR-γ) and CD36 gene expression and protein levels, and lower expression of mRNA coding for enzymes involved in de novo lipogenesis. GDNF-loaded nanoparticles were protective against short-term HFD-induced hepatic steatosis and attenuated liver fibrosis in mice with long-standing HFD-induced hepatic steatosis. They also suppressed the liver expression of steatosis-associated genes. In vitro, GDNF suppressed triglyceride accumulation in Hep G2 cells through enhanced p38 mitogen-activated protein kinase-dependent signaling and inhibition of PPAR-γ gene promoter activity. These results show that GDNF acts directly in the liver to protect against HFD-induced cellular stress and that GDNF may have a role in the treatment of nonalcoholic fatty liver disease.

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