Long-term treatment with acylated analogues of apelin-13 amide ameliorates diabetes and improves lipid profile of high-fat fed mice.

Journal article


O' Harte, F.P.M., Parthsarathy, V., Hogg, C and Flatt, P 2018. Long-term treatment with acylated analogues of apelin-13 amide ameliorates diabetes and improves lipid profile of high-fat fed mice. PLos ONE. 13 (8). https://doi.org/10.1371/journal.pone.0202350
AuthorsO' Harte, F.P.M., Parthsarathy, V., Hogg, C and Flatt, P
Abstract

Previous studies have shown that modified apelin analogues exhibited enzyme resistance in plasma and improved circulating half-life compared to apelin-13. This study investigated the antidiabetic effects of chronic administration of stable long acting fatty acid modified apelin analogues, namely, (Lys8GluPAL)apelin-13 amide and pGlu(Lys8GluPAL)apelin-13 amide, in high-fat fed obese-diabetic mice. Male NIH Swiss mice (groups n = 8) were maintained either on a high-fat diet (45% fat) from 8 to 28 weeks old, or control mice were fed a normal diet (10% fat). When diet induced obesity-diabetes was established after high-fat feeding, mice were injected i.p. once daily with apelin analogues, liraglutide (25 nmol/kg) or saline (controls). Administration of (Lys8GluPAL)apelin-13 amide and pGlu(Lys8GluPAL)apelin-13 amide for 28 days significantly reduced food intake and decreased body weight. Non-fasting glucose was reduced (p<0.01 to p<0.001) and plasma insulin concentrations increased (p<0.01 to p<0.001). This was accompanied by enhanced insulin responses (p<0.01 to p<0.001) and significant reductions in glucose excursion after oral (p<0.01) or i.p. (p<0.01) glucose challenges and feeding. Apelin analogues also significantly improved HbA1c (p<0.01), enhanced insulin sensitivity (p<0.01), reduced triglycerides (p<0.001), increased HDL-cholesterol (p<0.01) and decreased LDL-cholesterol (p<0.01), compared to high-fat fed saline treated control mice. Cholesterol levels were decreased (p<0.01) by pGlu(Lys8GluPAL)apelin-13 amide and both apelin treated groups showed improved bone mineral content, reduced fat deposits and increased plasma GLP-1. Daily treatment with liraglutide mirrored many of these changes (not on bone or adipose tissue), but unlike apelin analogues increased plasma amylase. Consumption of O2, production of CO2, respiratory exchange ratio and energy expenditure were improved by apelin analogues. These results indicate that long-term treatment with acylated analogues (Lys8GluPAL)apelin-13 amide and particularly pGlu(Lys8GluPAL)apelin-13 amide resulted in similar or enhanced therapeutic responses to liraglutide in high-fat fed mice. Fatty acid derived apelin analogues represent a new and exciting development in the treatment of obesity-diabetes.

Keywordsapelin-13; T2DM; obesity
Year2018
JournalPLos ONE
Journal citation13 (8)
PublisherPLOS
ISSN1932-6203
Digital Object Identifier (DOI)https://doi.org/10.1371/journal.pone.0202350
Web address (URL)http://europepmc.org/article/med/30157220
https://pure.ulster.ac.uk/en/publications/long-term-treatment-with-acylated-analogues-of-apelin-13-amide-am
http://hdl.handle.net/10545/624642
http://creativecommons.org/publicdomain/zero/1.0/
hdl:10545/624642
Output statusPublished
Publication dates29 Aug 2018
Publication process dates
Deposited01 Apr 2020
Accepted01 Aug 2018
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CC0 1.0 Universal

ContributorsUlster University
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