Exogenous acylated ghrelin promotes but un-acylated ghrelin prevents hepatic steatosis by modulating peripheral insulin resistance and hepatic oxidative and endoplasmic reticulum stress

Samah Alharbi; Refaat A. Eid

doi:10.22317/jcms.v7i3.998

Article Details

Exogenous acylated ghrelin promotes but un-acylated ghrelin prevents hepatic steatosis by modulating peripheral insulin resistance and hepatic oxidative and endoplasmic reticulum stress

Authors:

Samah Alharbi | Refaat A. Eid

Publisher:

Nab'a Al-Hayat Foundation for Medical Sciences and Health Care, Iraq

Journal:

Journal of Contemporary Medical Sciences Vol.7 Issue 3, pp.128-139

Document Type:

Article

Publication Date:

6/2021

Document Language:

English

Document ID (Org No.):

2001379418

pISSN:

2413-0516

DOI:

10.22317/jcms.v7i3.998

Keywords:

Abstract:

 Objectives: This study tested the effects of acylated (AG and un-acylated ghrelin (UAG) on hepatic lipid synthesis and insulin resistance (IR) from prospective to their effect on endoplasmic reticulum stress and investigated the possible underlying mechanisms.
Methods: Healthy rats were divided as 4 groups (n=12/each) as control, control + AG, control + UAG, and control + AG + UAG (1:1). GA or UAG were given subcutaneously (200 ng/kg/each) for 8 weeks.
Results: AG increased fasting levels of glucose and insulin resistance, increased hepatic glucose production, and impaired glucose and insulin tolerance. Besides, it increased serum levels of free fatty acids (FFAs), enhanced serum and hepatic levels of triglycerides and cholesterol, and increased lipid deposition in the livers of rats. Concomitantly, it stimulated the mRNA levels of SREBP1/2, fatty acid synthase, and protein levels of all arms of ER stress including Xbp-1, CHOP, ATF-6, and p-eIF2Î±, thus activating lipid synthesis and ER stress. It also reduced protein levels of p-IRS (Tyr612), p-Akt (Ser307), and increased levels of ROS, TNF-Î±, IL-6, and protein levels of cleaved caspase-12, p-IRS (Ser307), and p-JNK (The183/Tyr186) in ratsâ€™ livers. Administration of UAG alone or in combination with AG produced contradictory effects. However, both AG and UAG significantly increased mRNA levels of AMPK and PPARÎ± suggesting FAs oxidation.
Conclusion: AG induces hepatic steatosis and suppresses hepatic insulin signaling mainly by inducing peripheral IR that is associated with hepatic oxidative stress, inflammation, and ER stress. However, UAG alone or in combination exerts opposite effects.

Article Details

Exogenous acylated ghrelin promotes but un-acylated ghrelin prevents hepatic steatosis by modulating peripheral insulin resistance and hepatic oxidative and endoplasmic reticulum stress

Authors:

Samah Alharbi | Refaat A. Eid

Publisher:

Nab'a Al-Hayat Foundation for Medical Sciences and Health Care, Iraq

Journal:

Journal of Contemporary Medical Sciences Vol.7 Issue 3, pp.128-139

Document Type:

Article

Publication Date:

6/2021

Document Language:

English

Document ID (Org No.):

2001379418

pISSN:

2413-0516

DOI:

10.22317/jcms.v7i3.998

Ghrelin

Acylated

Insulin Resistance

Steatosis

Liver

Endoplasmic Reticulum

Oxidative Stress

Issues

Article Details

Authors: Samah Alharbi | Refaat A. Eid

Publisher: Nab'a Al-Hayat Foundation for Medical Sciences and Health Care, Iraq

Journal: Journal of Contemporary Medical Sciences Vol.7 Issue 3, pp.128-139

Document Type: Article

Publication Date: 6/2021

Document Language: English

Document ID (Org No.): 2001379418

pISSN: 2413-0516

DOI: 10.22317/jcms.v7i3.998

Issues

Authors:

Samah Alharbi | Refaat A. Eid

Publisher:

Nab'a Al-Hayat Foundation for Medical Sciences and Health Care, Iraq

Journal:

Journal of Contemporary Medical Sciences Vol.7 Issue 3, pp.128-139

Document Type:

Article

Publication Date:

6/2021

Document Language:

English

Document ID (Org No.):

2001379418

pISSN:

2413-0516

DOI:

10.22317/jcms.v7i3.998