Liraglutide Alleviates Hepatic Steatosis and Liver Injury in T2MD Rats via a GLP-1R Dependent AMPK Pathway.

Select Content Type
Clinical Guidelines
Authored By
Zhou R, Lin C, Cheng Y, Zhuo X, Li Q, Xu W, Zhao L, Yang L
Authored On
Interests
Gastroenterology
Emergency Medicine
Speciality
Gastroenterology
Emergency Medicine
Book Detail
volume
11
ISSN
1663-9812
Publication Date
Actions
Download in App
Event Data
{"article_title":"Liraglutide Alleviates Hepatic Steatosis and Liver Injury in T2MD Rats via a GLP-1R Dependent AMPK Pathway.","author":"\"Zhou, Rui , Lin, Chuman , Cheng, Yanzhen , Zhuo, Xiaoyun , Li, Qinghua , Xu, Wen , Zhao, Liang , Yang, Li\"","journal_title":"Frontiers in pharmacology","issn":"1663-9812 ; Print","isbn":"","publication_date":"20210304","volume":"11","issue":"","first_page":"600175","page_count":"","accession_number":"33746742","doi":"10.3389\/fphar.2020.600175","publisher":"Frontiers Media]","doctype":"Journal Article","subjects":"Endocrinology & Metabolism","interest_area":["Gastroenterology"," Emergency Medicine"],"abstract":"The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","url":"https:\/\/search.ebscohost.com\/login.aspx?direct=true&db=mdl&AN=33746742&authtype=shib&custid=ns346513","isPdfLink":true,"isSAML":false,"additionalInfo":{"Authored_By":"Zhou R, Lin C, Cheng Y, Zhuo X, Li Q, Xu W, Zhao L, Yang L","Journal_Info":"Publisher: Frontiers Media] Country of Publication: Switzerland NLM ID: 101548923 Publication Model: eCollection Cited Medium: Print ISSN: 1663-9812 (Print) Linking ISSN: 16639812 NLM ISO Abbreviation: Front Pharmacol Subsets: PubMed not MEDLINE","Publication_Type":"Journal Article","Published_Date":"2021-03-04","Source":"Frontiers in pharmacology [Front Pharmacol] 2021 Mar 04; Vol. 11, pp. 600175. Date of Electronic Publication: 2021 Mar 04 (Print Publication: 2020).","Languages":"English","Title_Abbreviations":"Frontiers in pharmacology","Volume":"11"},"header":{"DbId":"mdl","DbLabel":"MEDLINE Ultimate","An":"33746742","RelevancyScore":"854","PubType":"Academic Journal","PubTypeId":"academicJournal","PreciseRelevancyScore":"854.0263671875"},"plink":"https:\/\/search.ebscohost.com\/login.aspx?direct=true&site=eds-live&db=mdl&AN=33746742&authtype=shib&custid=ns346513&group=main&profile=eds","upload_link":"https:\/\/search.ebscohost.com\/login.aspx?direct=true&site=eds-live&db=mdl&AN=33746742&authtype=shib&custid=ns346513&group=main&profile=eds"}
ISSN
1663-9812 ; Print
IS_Ebsco
true
Upload Link
https://search.ebscohost.com/login.aspx?direct=true&db=mdl&AN=33746742&authtype=shib&custid=ns346513
Additional Info
["Zhou R, Lin C, Cheng Y, Zhuo X, Li Q, Xu W, Zhao L, Yang L","Publisher: Frontiers Media] Country of Publication: Switzerland NLM ID: 101548923 Publication Model: eCollection Cited Medium: Print ISSN: 1663-9812 (Print) Linking ISSN: 16639812 NLM ISO Abbreviation: Front Pharmacol Subsets: PubMed not MEDLINE","Journal Article","2021-03-04","Frontiers in pharmacology [Front Pharmacol] 2021 Mar 04; Vol. 11, pp. 600175. Date of Electronic Publication: 2021 Mar 04 (Print Publication: 2020).","English","Frontiers in pharmacology","11"]
Description
Non-alcoholic fatty liver disease (NAFLD), ranging from non-alcoholic fatty liver to non-alcoholic steatohepatitis, can be prevalent in patients with type 2 diabetes mellitus (T2DM). However, no antidiabetic drug has been approved for the treatment of NAFLD in T2DM patients. Multiple daily injections of basal-bolus insulin are often the final therapeutic option for T2DM. We found that insulin treatment aggravated hepatic steatosis and oxidative stress in Zucker diabetic fatty (ZDF) rats. In addition to glycaemic control, we demonstrated the stimulatory role of liraglutide in relieving hepatic steatosis and liver injury in ZDF rats. Interestingly, liraglutide could also alleviate insulin-aggravated hepatic fatty accumulation. The glucagon-like peptide-1 (GLP-1) agonists liraglutide and Ex-4 activated the expression of peroxisome proliferator-activated receptor alpha (PPARα) via a GLP-1 receptor-dependent 5' AMP-activated protein kinase pathway. As a nuclear transcription factor, PPARα could mediate the effect of GLP-1 in alleviating hepatic steatosis by differentially regulating the expression of its target genes, including acetyl CoA carboxylase and carnitine palmitoyl transferase la both in vitro and in vivo . Moreover, GLP-1 could relieve liver injury by decreasing oxidative stress stimulated by hepatic steatosis. Insulin might aggravate hepatic steatosis and liver injury by inhibiting GLP-1R expression. The findings indicate the feasibility of liraglutide treatment combined with basal insulin in attenuating hepatic steatosis and liver injury in ZDF rats. This knowledge, and the evidence for the underlying mechanism, provide a theoretical basis for the combination treatment recommended by the latest clinical practice guidelines for T2DM.<br /> (Copyright © 2021 Zhou, Lin, Cheng, Zhuo, Li, Xu, Zhao and Yang.)
Published Date