Obestatin protects and reverses nonalcoholic fatty liver disease and its associated insulin resistance in rats via inhibition of food intake, enhancing hepatic adiponectin signaling, and blocking ghrelin acylation

Abstract

This study investigated the ameliorative and protective effects of long-term obestatin administration (80 nmol/kg/ intraperitoneal injection (i.p.)) on the pathogenesis of high-fat diet (HFD) induced nonalcoholic fatty liver disease (NAFLD) in rats. Rats (n = 8/group) were divided as control, NAFLD, NAFLD + Simvastatin, NAFLD + obestatin, NAFLD then obestatin, and obestatin then NAFLD. Obestatin co -or post-therapy significantly reduced hepatomegaly and reversed hyperlipidemia, hepatic lipid accumulation, and insulin resistance (IR). Mechanistically obestatin treatments in these rats significantly prevented the increases in final body weights and food intake. Concomitantly, it enhanced circulatory adiponectin levels and hepatic signaling as evident by elevated hepatic protein levels of adiponectin receptors (adipoRII), carnitine palmitoyltransferase-1 (CPT-1), peroxisome proliferator-activated receptor- α (PPAR-α), and phosphor-AMPK (p-AMPK). In addition, obestatin enhanced total circulatory ghrelin levels and significantly increased deacylated ghrelin to acylated ghrelin (DAG/AG) ratio. These data suggest that obestatin reverses and protects against development or progression of NAFLD directly by modulating ghrelin and adiponectin signaling or indirectly by lowering food intake.

Keywords:

• Obestatin
• HFD
• NAFLD
• adiponectin
• ghrelin

Acknowledgement

The authors wish to thanks the technical staff of the animal house facilities at the College of Medicine at KKU for their help in the management, taking care, and feeding of the animals used in this study. In addition, the authors wish to thank the technical staff at the Department of Biochemistry and Department of physiology, College of Medicine in KKU for their help in some of the biochemical measurements in this study.

Disclosure statement

The authors declare that there are no conflict of interest.

Additional information

Funding

The authors declare that this study is funded by King Khalid University (KKU) through general research project under grant number [233].