RGD Reference Report - PEGylated Curcumin Derivative Attenuates Hepatic Steatosis via CREB/PPAR-γ/CD36 Pathway. - Rat Genome Database

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PEGylated Curcumin Derivative Attenuates Hepatic Steatosis via CREB/PPAR-γ/CD36 Pathway.

Authors: Liu, Yu  Cheng, Fei  Luo, Yuxuan  Zhan, Zhu  Hu, Peng  Ren, Hong  Tang, Huadong  Peng, Mingli 
Citation: Liu Y, etal., Biomed Res Int. 2017;2017:8234507. doi: 10.1155/2017/8234507. Epub 2017 Jul 9.
RGD ID: 401940144
Pubmed: PMID:28770225   (View Abstract at PubMed)
PMCID: PMC5523402   (View Article at PubMed Central)
DOI: DOI:10.1155/2017/8234507   (Journal Full-text)

Curcumin has the potential to cure dyslipidemia and nonalcoholic fatty liver disease (NAFLD). However, its therapeutic effects are curbed by poor bioavailability. Our previous work has shown that modification of curcumin with polyethylene glycol (PEG) improves blood concentration and tissue distribution. This study sought to investigate the role of a novel PEGylated curcumin derivative (Curc-mPEG454) in regulating hepatic lipid metabolism and to elucidate the underlying molecular mechanism in a high-fat-diet- (HFD-) fed C57BL/6J mouse model. Mice were fed either a control chow diet (D12450B), an HFD (D12492) as the NAFLD model, or an HFD with Curc-mPEG454 administered by intraperitoneal injection at 50 mg/kg or 100 mg/kg for 16 weeks. We found that Curc-mPEG454 significantly lowered the body weight and serum triglyceride (TG) levels and reduced liver lipid accumulation in HFD-induced NAFLD mice. It was also shown that Curc-mPEG454 suppressed the HFD-induced upregulated expression of CD36 and hepatic peroxisome proliferator activated receptor-γ (PPAR-γ), a positive regulator of CD36. Moreover, Curc-mPEG454 dramatically activated cAMP response element-binding (CREB) protein, which negatively controls hepatic PPAR-γ expression. These findings suggest that Curc-mPEG454 reverses HFD-induced hepatic steatosis via the activation of CREB inhibition of the hepatic PPAR-γ/CD36 pathway, which may be an effective therapeutic for high-fat-diet-induced NAFLD.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CREB1Humannon-alcoholic fatty liver treatmentISOCreb1 (Mus musculus) RGD 
Creb1Ratnon-alcoholic fatty liver treatmentISOCreb1 (Mus musculus) RGD 
Creb1Mousenon-alcoholic fatty liver treatmentIEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Creb1  (cAMP responsive element binding protein 1)

Genes (Mus musculus)
Creb1  (cAMP responsive element binding protein 1)

Genes (Homo sapiens)
CREB1  (cAMP responsive element binding protein 1)


Additional Information