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
References
Apr 15, 1992·The Biochemical Journal·A C RustanC A Drevon
May 1, 1991·Diabetes·P FaschingH Vierhapper
Aug 21, 1987·Science·L H StorlienW S Pascoe
Jul 1, 1966·Proceedings of the National Academy of Sciences of the United States of America·J R WilliamsonP W Felts
Dec 1, 1995·Nature Medicine·R C FrederichJ S Flier
Jul 20, 1996·Lancet·J F CaroR V Considine
Sep 3, 1996·Proceedings of the National Academy of Sciences of the United States of America·C W Miller, J M Ntambi
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·B M FormanR M Evans
Sep 24, 1999·The Biochemical Journal·R K BergeA C Rustan
Oct 28, 1999·The American Journal of Clinical Nutrition·T A MoriL J Beilin
Oct 26, 2002·The American Journal of Clinical Nutrition·Richard J WoodmanLawrence J Beilin
Aug 23, 2003·Endocrinology·Mark J HolnessMary C Sugden
Apr 27, 2004·Nature Medicine·Seung-Hoi KooMarc Montminy
Dec 21, 2004·Biochemical and Biophysical Research Communications·Gabriela SuchankovaThomas W Gettys
Jan 1, 2005·Pharmacology & Therapeutics·Charles N Serhan
Jan 25, 2005·Bioorganic & Medicinal Chemistry Letters·Keiko YamamotoSachiko Yamada
Mar 2, 2005·Lipids·Jana RuzickovaJan Kopecky
Mar 22, 2005·The Biochemical Journal·Brian L KnightGeoffrey F Gibbons
May 3, 2005·The Journal of Clinical Investigation·Kathryn E Wellen, Gökhan S Hotamisligil
Jul 14, 2005·Annual Review of Nutrition·Harini Sampath, James M Ntambi
Sep 10, 2005·Journal of Lipid Research·Saverio CintiMartin S Obin
Oct 6, 2005·Diabetologia·P FlachsJ Kopecky
Oct 11, 2005·The Journal of Nutritional Biochemistry·Yolanda B Lombardo, Adriana G Chicco
Jan 7, 2006·Diabetologia·P FlachsJ Kopecky
Jun 3, 2006·Endocrinology·M M HaluzikM Haluzik
Jun 20, 2006·Diabetologia·J TodoricT M Stulnig
Jul 1, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Davide MainieriAbdul G Dulloo
Sep 16, 2006·Current Opinion in Pharmacology·Catherine FiévetBart Staels
Dec 15, 2006·Nature·Leonard Guarente
Dec 15, 2006·Nature·Jean-Pierre Després, Isabelle Lemieux
Jan 26, 2007·Diabetes·Susanne NeschenGerald I Shulman
Feb 23, 2007·The Biochemical Journal·Margarita Teran-GarciaThomas W Gettys
Mar 30, 2007·Diabetologia·X Yang, U Smith
May 23, 2007·The New England Journal of Medicine·Steven E Nissen, Kathy Wolski
Jan 18, 2008·Nature Reviews. Molecular Cell Biology·Deborah M Muoio, Christopher B Newgard
Feb 28, 2008·PloS One·Linda M SandersonSander Kersten
Citations
Mar 12, 2009·Diabetologia·O KudaJ Kopecky
Sep 17, 2011·The British Journal of Nutrition·Fatima Kasbi ChadliKhadija Ouguerram
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
Oct 18, 2011·Metabolic Syndrome and Related Disorders·Darshan S KelleyDavid Siegel
May 17, 2011·Lipids in Health and Disease·Ricardo EguchiLila M Oyama
Sep 8, 2010·Lipids in Health and Disease·Karen M O'SheaWilliam C Stanley
Jun 16, 2012·PloS One·Martin RossmeislJan Kopecky
Feb 15, 2013·PloS One·Mirjam LuijtenThomas B Knudsen
Apr 25, 2013·PloS One·Fatima Kasbi ChadliKhadija Ouguerram
Jun 26, 2012·Expert Opinion on Drug Discovery·Yonggang MaGanesh V Halade
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
May 9, 2016·The Journal of Nutritional Biochemistry·Ulrike LiisbergLise Madsen
Jul 8, 2015·Biochimie·Jana PavlisovaMartin Rossmeisl
Mar 5, 2013·Biochimica Et Biophysica Acta·Pavel FlachsJan Kopecky
Feb 20, 2015·Analytical and Bioanalytical Chemistry·Peter SjövallMorten Bryhn
Oct 15, 2014·Biochimica Et Biophysica Acta·Mojgan MasoodiJan Kopecky
May 9, 2016·European Journal of Applied Physiology·Eric RivasVic Ben-Ezra
Sep 25, 2014·PloS One·Milos LazicDorothy D Sears
Oct 23, 2015·Archives of Animal Nutrition·Maria R C de GodoyDavid L Harmon
Feb 7, 2015·PloS One·Lisa K PhilpGary A Wittert
May 18, 2016·PloS One·Olga HorakovaJan Kopecky
Dec 7, 2013·International Journal of Obesity : Journal of the International Association for the Study of Obesity·J S TeodoroJ Kopecký
Jul 23, 2011·Diabetologia·P FlachsJ Kopecky
Jan 26, 2020·International Journal of Molecular Sciences·Anamaria BalićZrinka Bukvić Mokos
Feb 8, 2019·Applied Microbiology and Biotechnology·Sebastián CerminatiMaría Eugenia Castelli
Apr 17, 2020·Molecular Nutrition & Food Research·Pan ZhuangJingjing Jiao
Jul 22, 2015·The Journal of Membrane Biology·Val Andrew FajardoA Russell Tupling
May 16, 2019·Lipids·Judith LauvaiLutz Graeve
Dec 14, 2012·Physiological Research·P JanovskáJ Kopecký
Sep 24, 2010·The Journal of Nutrition·Nishan S KalupahanaNaima Moustaid-Moussa
Oct 8, 2020·Nutrients·Even FjæreLise Madsen
Nov 25, 2019·The Journal of Nutritional Biochemistry·Danyelle M LiddleLindsay E Robinson
Jul 6, 2020·Life Sciences·Licai ChengYinghua Yu
Mar 11, 2011·Nutrition & Metabolism·Matam Vijay-KumarVijay Ganji