Endocrine

, Volume 43, Issue 2, pp 376–386 | Cite as

Administration of ghrelin improves inflammation, oxidative stress, and apoptosis during and after non-alcoholic fatty liver disease development

  • Yan Li
  • Jie Hai
  • Lake Li
  • Xuehui Chen
  • Hua Peng
  • Meng Cao
  • Qinggui Zhang
Original Article
First Online:
Received:
Accepted:

Abstract

We aim to investigate the preventive and therapeutic effects of ghrelin on a rat NAFLD model and possible underlying mechanism. Sprague–Dawley rats were fed with high-fat diet for 8 weeks to induce NAFLD. A group of rats were also treated with ghrelin throughout the NAFLD induction. After 8 weeks, rats were sacrificed for liver injury measurements. Rats with NAFLD showed obvious histological changes including necrosis and inflammation foci, elevated serum enzyme (ALT and AST) levels, dysregulated hepatic lipid metabolism, increased formation of oxidative stress, and lipid peroxidation markers, up-regulated levels of pro-inflammatory cytokines and apoptotic cells in the liver. Treatment of ghrelin improved liver injury through counter-acting those events. The improvement of ghrelin was accompanied with a restoration of LKB1/AMPK and PI3 K/Akt pathways. Ghrelin treatment alone did not influence the healthy rat liver. In addition, “therapeutic” ghrelin administration (2 weeks) after the establishment of early NAFLD symptoms (4 weeks) in rats further proved the beneficial effects of ghrelin. In conclusion, administration of ghrelin could attenuate NAFLD-induced liver injury, oxidative stress, inflammation, and apoptosis partly through the action of LKB1/AMPK and PI3 K/Akt pathways.

Keywords

NAFLD Ghrelin Liver injury AMPK 

Abbreviations

ALT

Alanine aminotransferase

AMPK

AMP-activated protein kinase

AST

Aspartate aminotransferase

CYP2E1

Cytochrome P450 2E1

ELISA

Enzyme-linked immunosorbent assay

GH

Growth hormone

IL

Interleukin

MDA

Malondialdehyde

NAFLD

Non-alcoholic fatty liver disease

PNPLA3

Patatin-like phospholipase domain-containing protein 3

TNF-α

Tumor necrosis factor alpha

TUNEL

Terminal deoxynucleotidyl transferase dUTP-nick end labeling

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Notes

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Yan Li
    • 1
  • Jie Hai
    • 1
  • Lake Li
    • 1
  • Xuehui Chen
    • 1
  • Hua Peng
    • 1
  • Meng Cao
    • 1
  • Qinggui Zhang
    • 1
  1. 1.Department of Endocrinology, First Affiliated HospitalXinxiang Medical UniversityXinxiang CityChina

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