Prevention and reversal of obesity and glucose intolerance in mice by DHA derivatives

Obesity
Martin RossmeislJan Kopecky

Abstract

The n-3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exert hypolipidemic effects and prevent development of obesity and insulin resistance in animals fed high-fat diets. We sought to determine the efficacy of alpha-substituted DHA derivatives as lipid-lowering, antiobesity, and antidiabetic agents. C57BL/6 mice were given a corn oil-based high-fat (35% weight/weight) diet (cHF), or cHF with 1.5% of lipids replaced with alpha-methyl DHA ethyl ester (Substance 1), alpha-ethyl DHA ethyl ester (Substance 2), alpha,alpha-di-methyl DHA ethyl ester (Substance 3), or alpha-thioethyl DHA ethyl ester (Substance 4) for 4 months. Plasma markers of glucose and lipid metabolism, glucose tolerance, morphology, tissue lipid content, and gene regulation were characterized. The cHF induced obesity, hyperlipidemia, impairment of glucose homeostasis, and adipose tissue inflammation. Except for Substance 3, all other substances prevented weight gain and Substance 2 exerted the strongest effect (63% of cHF-controls). Glucose intolerance was significantly prevented (~67% of cHF) by both Substance 1 and Substance 2. Moreover, Substance 2 lowered fasting glycemia, plasma insulin, triacylglycerols, ...Continue Reading

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Citations

Aug 25, 2009·The Proceedings of the Nutrition Society·Jan KopeckyMorten Bryhn
May 5, 2011·International Journal of Obesity : Journal of the International Association for the Study of Obesity·D MedrikovaJ Kopecky
May 17, 2011·Lipids in Health and Disease·Ricardo EguchiLila M Oyama
Jan 18, 2012·Journal of Neurochemistry·Sunita GuptaAnnadora J Bruce-Keller
Sep 29, 2011·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·A G Dulloo
May 17, 2014·Journal of Cellular and Molecular Medicine·Cezary WójcikEduard Poels
Oct 15, 2014·Biochimica Et Biophysica Acta·Mojgan MasoodiJan Kopecky
Dec 7, 2013·International Journal of Obesity : Journal of the International Association for the Study of Obesity·J S TeodoroJ Kopecký
Jan 26, 2020·International Journal of Molecular Sciences·Anamaria BalićZrinka Bukvić Mokos
Feb 8, 2019·Applied Microbiology and Biotechnology·Sebastián CerminatiMaría Eugenia Castelli
Jul 22, 2015·The Journal of Membrane Biology·Val Andrew FajardoA Russell Tupling

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