A sustained increase in plasma NEFA upregulates the Toll-like receptor network in human muscle

Diabetologia
Sophie E HusseyNicolas Musi

Abstract

Insulin-sensitive tissues (muscle, liver) of individuals with obesity and type 2 diabetes mellitus are in a state of low-grade inflammation, characterised by increased Toll-like receptor (TLR) expression and TLR-driven signalling. However, the cause of this mild inflammatory state is unclear. We tested the hypothesis that a prolonged mild increase in plasma NEFA will increase TLR expression and TLR-driven signalling (nuclear factor κB [NFκB] and mitogen-activated kinase [MAPK]) and impair insulin action in muscle of lean healthy individuals. Twelve lean, normal-glucose-tolerant participants were randomised to receive a 48 h infusion (30 ml/h) of saline or Intralipid followed by a euglycaemic-hyperinsulinaemic clamp. Vastus lateralis muscle biopsies were performed before and during the clamp. Lipid infusion impaired insulin-stimulated IRS-1 tyrosine phosphorylation and reduced peripheral insulin sensitivity (p < 0.01). The elevation in circulating NEFA increased expression of TLR3, TLR4 and TLR5, and several MAPK (MAPK8, MAP4K4, MAP2K3) and inhibitor of κB kinase-NFκB (CHUK [IKKA], c-REL [REL] and p65 [RELA, NFKB3, p65]) signalling genes (p < 0.05). The lipid infusion also increased extracellular signal-regulated kinase (ERK) ph...Continue Reading

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References

Jan 23, 1999·The Journal of Clinical Investigation·A DresnerG I Shulman
Jan 15, 2002·The Journal of Clinical Endocrinology and Metabolism·Yolanta T KruszynskaJerrold M Olefsky
Sep 28, 2002·The Journal of Biological Chemistry·Zhanguo GaoJianping Ye
Aug 6, 2005·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Bankim A BhattRobert M O'Doherty
Jun 20, 2006·Biochemical and Biophysical Research Communications·Min Jeong SongJae Bum Kim
Oct 21, 2006·The Journal of Clinical Investigation·Hang ShiJeffrey S Flier
Oct 26, 2006·The Journal of Clinical Endocrinology and Metabolism·Mireille J SerlieHans P Sauerwein
Nov 9, 2006·American Journal of Physiology. Endocrinology and Metabolism·S J CreelyS Kumar
May 11, 2007·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·John J DubeRobert M O'Doherty
Jan 2, 2008·European Journal of Endocrinology·Bodil VistisenBente Stallknecht
Sep 5, 2008·The Journal of Clinical Investigation·Simon SchenkJerrold M Olefsky
Jul 2, 2009·The Journal of Clinical Endocrinology and Metabolism·Zhenqi LiuEugene J Barrett
Aug 27, 2010·American Journal of Physiology. Endocrinology and Metabolism·Puntip TantiwongNicolas Musi
Oct 6, 2010·Advances in Experimental Medicine and Biology·Jacek BielawskiAlicja Bielawska
May 23, 2012·Metabolism: Clinical and Experimental·Linda H WuVedrana S Susulic
Nov 9, 2012·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Mette LadefogedAnn Maria Kruse Hansen
Dec 22, 2012·Diabetes·Marieke G SchoonemanMaarten R Soeters
Jul 3, 2013·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Chan-Hee JungJi-Oh Mok

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Citations

Feb 26, 2016·Food & Function·Sergio Montserrat-de la PazFrancisco J G Muriana
Apr 5, 2016·Cancer Cell International·Yuanyuan QinLiza Makowski
Jun 26, 2015·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Olesja RitterMichael Roden
Dec 4, 2014·International Journal of Obesity : Journal of the International Association for the Study of Obesity·J F TrepanowskiK A Varady
May 17, 2018·Physiological Reviews·Sofiya GanchevaMichael Roden
Nov 3, 2016·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Oh Sung KwonMicah J Drummond
Apr 9, 2015·American Journal of Physiology. Endocrinology and Metabolism·Cathryn M KolkaRichard N Bergman
May 15, 2015·American Journal of Physiology. Endocrinology and Metabolism·Oh Sung KwonMicah J Drummond
Aug 23, 2017·Annual Review of Nutrition·Jessica C RalstonHelen M Roche
Oct 12, 2018·Nutrients·Cheng-Shyuan RauChing-Hua Hsieh
Apr 23, 2020·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Hong WangSanna Lehtonen
Jan 27, 2017·BMC Musculoskeletal Disorders·Kaisa MannerkorpiJan L Bjersing
Aug 4, 2019·Trends in Endocrinology and Metabolism : TEM·Sisitha U JayasingheFrancesca Amati

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