Lipid-overloaded enlarged adipocytes provoke insulin resistance independent of inflammation

Molecular and Cellular Biology
Jong In KimJae Bum Kim

Abstract

In obesity, adipocyte hypertrophy and proinflammatory responses are closely associated with the development of insulin resistance in adipose tissue. However, it is largely unknown whether adipocyte hypertrophy per se might be sufficient to provoke insulin resistance in obese adipose tissue. Here, we demonstrate that lipid-overloaded hypertrophic adipocytes are insulin resistant independent of adipocyte inflammation. Treatment with saturated or monounsaturated fatty acids resulted in adipocyte hypertrophy, but proinflammatory responses were observed only in adipocytes treated with saturated fatty acids. Regardless of adipocyte inflammation, hypertrophic adipocytes with large and unilocular lipid droplets exhibited impaired insulin-dependent glucose uptake, associated with defects in GLUT4 trafficking to the plasma membrane. Moreover, Toll-like receptor 4 mutant mice (C3H/HeJ) with high-fat-diet-induced obesity were not protected against insulin resistance, although they were resistant to adipose tissue inflammation. Together, our in vitro and in vivo data suggest that adipocyte hypertrophy alone may be crucial in causing insulin resistance in obesity.

References

Aug 1, 1969·The Journal of Clinical Endocrinology and Metabolism·C Esanu, G A Bray
Aug 8, 2001·The Journal of Clinical Investigation·J K KimG I Shulman
Aug 3, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rolando B CeddiaGary Sweeney
Nov 26, 2002·Nature·Jiro HirosumiGökhan S Hotamisligil
Jul 4, 2003·The Journal of Clinical Investigation·Aimin XuGarth J S Cooper
Dec 18, 2003·The Journal of Clinical Investigation·Stuart P WeisbergAnthony W Ferrante
Dec 18, 2003·The Journal of Clinical Investigation·Haiyan XuHong Chen
May 8, 2004·The Journal of Biological Chemistry·Matthias BlüherC Ronald Kahn
Jun 8, 2004·The Journal of Clinical Endocrinology and Metabolism·Erin E Kershaw, Jeffrey S Flier
Jul 2, 2004·Nature Reviews. Immunology·Shizuo Akira, Kiyoshi Takeda
Nov 25, 2004·Diabetes·Harald StaigerHans-Ulrich Häring
Feb 3, 2005·Nature Medicine·Melek C ArkanMichael Karin
Aug 9, 2005·The Journal of Biological Chemistry·M T Audrey NguyenJerrold M Olefsky
Jun 7, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Margareta JernåsMalin Lönn
Oct 21, 2006·The Journal of Clinical Investigation·Hang ShiJeffrey S Flier
Jan 4, 2007·The Journal of Clinical Investigation·Carey N LumengAlan R Saltiel
Jan 11, 2007·Biochemical and Biophysical Research Communications·Takayoshi SuganamiYoshihiro Ogawa
May 15, 2007·Gastroenterology·Steven E ShoelsonAfia Naaz
May 8, 2008·Cell Metabolism·Kyle L HoehnDavid E James
Sep 11, 2008·Current Opinion in Genetics & Development·Cynthia Hong, Peter Tontonoz
Oct 8, 2008·Nature Clinical Practice. Endocrinology & Metabolism·Justin I Odegaard, Ajay Chawla
Feb 12, 2010·Stem Cell Reviews and Reports·Tianshu FengMichal Opas
Mar 2, 2011·PloS One·Nikolaos PsychogiosDavid S Wishart
Jan 17, 2012·Journal of Cell Science·Jacqueline StöckliDavid E James
Jan 18, 2013·PloS One·Angela SciacquaGiorgio Sesti
Jun 6, 2013·American Journal of Physiology. Endocrinology and Metabolism·Michael S F WiedemannDaniel Konrad

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Citations

May 5, 2016·Adipocyte·Sara Palacios-OrtegaFermín I Milagro
Feb 6, 2016·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Timothy P Fitzgibbons, Michael P Czech
Nov 11, 2015·Nature Reviews. Endocrinology·Denise E Lackey, Jerrold M Olefsky
Sep 26, 2015·International Journal of Obesity : Journal of the International Association for the Study of Obesity·A WeidemannF Weih
May 6, 2016·Frontiers in Endocrinology·Sung Sik ChoeJae Bum Kim
Jun 13, 2015·Diabetologia·Raziel Rojas-RodriguezTiffany A Moore Simas
Apr 26, 2016·Biochemical and Biophysical Research Communications·Björn HanssonKarin G Stenkula
Aug 5, 2016·Translational Research : the Journal of Laboratory and Clinical Medicine·Nicole G GrünThomas M Stulnig
Oct 1, 2016·Current Obesity Reports·David H IpsenJens Lykkesfeldt
Nov 20, 2016·International Journal of Obesity : Journal of the International Association for the Study of Obesity·K Beltran, K L Herbst
Feb 17, 2017·The Journal of Clinical Endocrinology and Metabolism·Ninna Schiøler HansenChrista Broholm
Mar 9, 2018·The Journal of Experimental Biology·Panna TandonJames E N Minchin
Apr 13, 2018·The Journal of Endocrinology·Ruben RodriguezRudy M Ortiz
Sep 20, 2017·Journal of Cellular Physiology·Flávia de T FriasAlice C Rodrigues
Jun 8, 2018·The Journal of Endocrinology·Clara LefrancAurelie Nguyen Dinh Cat
Aug 3, 2018·European Journal of Heart Failure·Gijs van WoerdenMichiel Rienstra
Aug 3, 2018·Journal of Molecular Endocrinology·Louise K MetcalfeNigel Turner
Jul 4, 2019·American Journal of Physiology. Cell Physiology·Melissa A FulhamPranoti Mandrekar
Jun 18, 2017·The EMBO Journal·Alexandros VegiopoulosStephan Herzig
Feb 6, 2020·Metabolites·Inês BrandãoRosário Monteiro
Mar 14, 2019·The Journal of Experimental Medicine·Hernandez Moura SilvaJuan J Lafaille
Mar 23, 2018·International Journal of Molecular Sciences·Laura A ForneyTara M Henagan
May 16, 2019·International Journal of Molecular Sciences·Michele LongoClaudia Miele
May 12, 2019·International Journal of Molecular Sciences·Young-Je Kim, Un Ju Jung
Sep 10, 2019·Frontiers in Endocrinology·Emilia Sokolowska, Agnieszka Blachnio-Zabielska
Feb 8, 2020·International Journal of Molecular Sciences·Angelina Vladimirovna PakhomovaEvgenii Germanovich Skurikhin
Mar 1, 2017·The Journal of Biological Chemistry·Nicole K H YiewNeal L Weintraub
Aug 1, 2018·Cell Death Discovery·María Cecilia LiraMaría Fernanda Rubio
Jun 9, 2020·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Anastasia OtamasRamzi A Ajjan

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