Publications
Representative Publications
Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature. 1997 Oct 9;389(6651):610-4. doi: 10.1038/39335. PMID: 9335502.
Hirosumi J, Tuncman G, Chang L, Görgün CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS. A central role for JNK in obesity and insulin resistance. Nature. 2002 Nov 21;420(6913):333-6. doi: 10.1038/nature01137. doi: 10.1038/s41586-023-06285-0. PMID: 12447443.
Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Görgün C, Glimcher LH, Hotamisligil GS. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004 Oct 15;306(5695):457-61. doi: 10.1126/science.1103160. PMID: 15486293.
Wellen KE, Fucho R, Gregor MF, Furuhashi M, Morgan C, Lindstad T, Vaillancourt E, Gorgun CZ, Saatcioglu F, Hotamisligil GS. Coordinated regulation of nutrient and inflammatory responses by STAMP2 is essential for metabolic homeostasis. Cell. 2007 May 4;129(3):537-48. doi: 10.1016/j.cell.2007.02.049. PMID: 17482547; PMCID: PMC2408881.
Cao H, Gerhold K, Mayers JR, Wiest MM, Watkins SM, Hotamisligil GS. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell. 2008 Sep 19;134(6):933-44. doi: 10.1016/j.cell.2008.07.048. PMID: 18805087; PMCID: PMC2728618.
Erbay E, Babaev VR, Mayers JR, Makowski L, Charles KN, Snitow ME, Fazio S, Wiest MM, Watkins SM, Linton MF, Hotamisligil GS. Reducing endoplasmic reticulum stress through a macrophage lipid chaperone alleviates atherosclerosis. Nature Medicine. 2009 Dec;15(12):1383-91. doi: 10.1038/nm.2067. Epub 2009 Nov 29. Erratum in: Nat Med. 2010 Feb;16(2):237. PMID: 19966778; PMCID: PMC2790330.
Nakamura T, Furuhashi M, Li P, Cao H, Tuncman G, Sonenberg N, Gorgun CZ, Hotamisligil GS. Double-stranded RNA-dependent protein kinase links pathogen sensing with stress and metabolic homeostasis. Cell. 2010 Feb 5;140(3):338-48. doi: 10.1016/j.cell.2010.01.001. PMID: 20144759; PMCID: PMC2820414.
Yang L, Li P, Fu S, Calay ES, Hotamisligil GS. Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance. Cell Metabolism. 2010 Jun 9;11(6):467-78. doi: 10.1016/j.cmet.2010.04.005. PMID: 20519119; PMCID: PMC2881480.
Fu S, Yang L, Li P, Hofmann O, Dicker L, Hide W, Lin X, Watkins SM, Ivanov AR, Hotamisligil GS. Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity. Nature. 2011 May 26;473(7348):528-31. doi: 10.1038/nature09968. Epub 2011 May 1. PMID: 21532591; PMCID: PMC3102791.
Cao H, Sekiya M, Ertunc ME, Burak MF, Mayers JR, White A, Inouye K, Rickey LM, Ercal BC, Furuhashi M, Tuncman G, Hotamisligil GS. Adipocyte lipid chaperone AP2 is a secreted adipokine regulating hepatic glucose production. Cell Metabolism. 2013 May 7;17(5):768-78. doi: 10.1016/j.cmet.2013.04.012. PMID: 23663740; PMCID: PMC3755450.
Arruda AP, Pers BM, Parlakgül G, Güney E, Inouye K, Hotamisligil GS. Chronic enrichment of hepatic endoplasmic reticulum-mitochondria contact leads to mitochondrial dysfunction in obesity. Nature Medicine. 2014 Dec;20(12):1427-35. doi: 10.1038/nm.3735. Epub 2014 Nov 24. PMID: 25419710; PMCID: PMC4412031.
Yang L, Calay ES, Fan J, Arduini A, Kunz RC, Gygi SP, Yalcin A, Fu S, Hotamisligil GS. METABOLISM. S-Nitrosylation links obesity-associated inflammation to endoplasmic reticulum dysfunction. Science. 2015 Jul 31;349(6247):500-6. doi: 10.1126/science.aaa0079. PMID: 26228140; PMCID: PMC4573582.
Widenmaier SB, Snyder NA, Nguyen TB, Arduini A, Lee GY, Arruda AP, Saksi J, Bartelt A, Hotamisligil GS. NRF1 Is an ER Membrane Sensor that Is Central to Cholesterol Homeostasis. Cell. 2017 Nov 16;171(5):1094-1109.e15. doi: 10.1016/j.cell.2017.10.003. PMID: 29149604.
Bartelt A, Widenmaier SB, Schlein C, Johann K, Goncalves RLS, Eguchi K, Fischer AW, Parlakgül G, Snyder NA, Nguyen TB, Bruns OT, Franke D, Bawendi MG, Lynes MD, Leiria LO, Tseng YH, Inouye KE, Arruda AP, Hotamisligil GS. Brown adipose tissue thermogenic adaptation requires Nrf1-mediated proteasomal activity. Nature Medicine. 2018 Mar;24(3):292-303. doi: 10.1038/nm.4481. Epub 2018 Feb 5. PMID: 29400713; PMCID: PMC5839993.
Tirosh A, Tuncman G, Calay ES, Rathaus M, Ron I, Tirosh A, Yalcin A, Lee YG, Livne R, Ron S, Minsky N, Arruda AP, Hotamisligil GS. Intercellular Transmission of Hepatic ER Stress in Obesity Disrupts Systemic Metabolism. Cell Metab. 2021 Feb 2;33(2):319-333.e6. doi: 10.1016/j.cmet.2020.11.009. Epub 2020 Dec 18. Erratum in: Cell Metabolism. 2021 Aug 3;33(8):1716. doi: 10.1016/j.cmet.2021.07.005. PMID: 33340456; PMCID: PMC7858244.
Prentice KJ, Saksi J, Robertson LT, Lee GY, Inouye KE, Eguchi K, Lee A, Cakici O, Otterbeck E, Cedillo P, Achenbach P, Ziegler A-G, Calay ES, Engin F, Hotamisligil GS. A hormone complex of FABP4 and nucleoside kinases regulates islet function. Nature. 2021 Dec;600(7890):720-726. doi: 10.1038/s41586-021-04137-3. PMID: 34880500
Inouye KE, Prentice KJ, Lee A, Wang ZB, Dominguez-Gonzalez C, Chen MX, Riveros JK, Burak MF, Lee GY, Hotamışlıgil GS. Endothelial-derived FABP4 constitutes the majority of basal circulating hormone and regulates lipolysis-driven insulin secretion. JCI Insight. 2023 Jul 24;8(14):e164642. doi: 10.1172/jci.insight.164642. PMID: 37279064
Parlakgül G, Pang S, Artico LL, Min N, Cagampan E, Villa R, Goncalves RLS, Lee GY, Xu CS, Hotamışlıgil GS, Arruda AP. Spatial mapping of hepatic ER and mitochondria architecture reveals zonated remodeling in fasting and obesity. Nat Commun. 2024 May 10;15(1):3982. doi: 10.1038/s41467-024-48272-7. PMID: 38729945
Baazim H, Koyuncu E, Tuncman G, Burak MF, Merkel L, Bahour N, Karabulut ES, Lee GY, Hanifehnezhad A, Karagoz ZF, Földes K, Engin I, Erman AG, Oztop S, Filazi N, Gul B, Ceylan A, Cinar OO, Can F, Kim H, Al-Hakeem A, Li H, Semerci F, Lin X, Yilmaz E, Ergonul O, Ozkul A, Hotamisligil GS. FABP4 as a therapeutic host target controlling SARS-CoV-2 infection. EMBO Mol Med. 2025 Jan 22. doi: 10.1038/s44321-024-00188-x. PMID: 39843629
Translational Studies
Furuhashi M, Tuncman G, Görgün CZ, Makowski L, Atsumi G, Vaillancourt E, Kono K, Babaev VR, Fazio S, Linton MF, Sulsky R, Robl JA, Parker RA, Hotamisligil GS. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature. 2007 Jun 21;447(7147):959-65. doi: 10.1038/nature05844. Epub 2007 Jun 6. PMID: 17554340; PMCID: PMC4076119.
Mozaffarian D, Cao H, King IB, Lemaitre RN, Song X, Siscovick DS, Hotamisligil GS. Trans-palmitoleic acid, metabolic risk factors, and new-onset diabetes in U.S. adults: a cohort study. Ann Intern Medicine. 2010 Dec 21;153(12):790-9. doi: 10.7326/0003-4819-153-12-201012210-00005. PMID: 21173413; PMCID: PMC3056495.
Engin F, Yermalovich A, Nguyen T, Hummasti S, Fu W, Eizirik DL, Mathis D, Hotamisligil GS. Restoration of the unfolded protein response in pancreatic β cells protects mice against type 1 diabetes. Sci Transl Med. 2013 Nov 13;5(211):211ra156. doi: 10.1126/scitranslmed.3006534. Erratum in: Science Translational Medicine. 2013 Dec 4;5(214):214er11. Ngyuen, Truc [corrected to Nguyen, Truc]. PMID: 24225943; PMCID: PMC4169117.
Fu S, Yalcin A, Lee GY, Li P, Fan J, Arruda AP, Pers BM, Yilmaz M, Eguchi K, Hotamisligil GS. Phenotypic assays identify azoramide as a small-molecule modulator of the unfolded protein response with antidiabetic activity. Science Translational Medicine. 2015 Jun 17;7(292):292ra98. doi: 10.1126/scitranslmed.aaa9134. PMID: 26084805; PMCID: PMC5063051.
Burak MF, Inouye KE, White A, Lee A, Tuncman G, Calay ES, Sekiya M, Tirosh A, Eguchi K, Birrane G, Lightwood D, Howells L, Odede G, Hailu H, West S, Garlish R, Neale H, Doyle C, Moore A, Hotamisligil GS. Development of a therapeutic monoclonal antibody that targets secreted fatty acid-binding protein aP2 to treat type 2 diabetes. Science Translational Medicine. 2015 Dec 23;7(319):319ra205. doi: 10.1126/scitranslmed.aac6336. Epub 2015 Dec 23. PMID: 26702093.
Tirosh A, Calay ES, Tuncman G, Claiborn KC, Inouye KE, Eguchi K, Alcala M, Rathaus M, Hollander KS, Ron I, Livne R, Heianza Y, Qi L, Shai I, Garg R, Hotamisligil GS. The short-chain fatty acid propionate increases glucagon and FABP4 production, impairing insulin action in mice and humans. Science Translational Medicine. 2019 Apr 24;11(489):eaav0120. doi: 10.1126/scitranslmed.aav0120. PMID: 31019023.
Reviews & Commentaries
Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 2010 Mar 19;140(6):900-17. doi: 10.1016/j.cell.2010.02.034. PMID: 20303879; PMCID: PMC2887297.
Fu S, Watkins SM, Hotamisligil GS. The role of endoplasmic reticulum in hepatic lipid homeostasis and stress signaling. Cell Metabolism. 2012 May 2;15(5):623-34. doi: 10.1016/j.cmet.2012.03.007. PMID: 22560215.
Arruda AP, Hotamisligil GS. Calcium Homeostasis and Organelle Function in the Pathogenesis of Obesity and Diabetes. Cell Metabolism. 2015 Sep 1;22(3):381-97. doi: 10.1016/j.cmet.2015.06.010. Epub 2015 Jul 16. PMID: 26190652; PMCID: PMC4558313.
Hotamisligil GS, Bernlohr DA. Metabolic functions of FABPs–mechanisms and therapeutic implications. Nature Reviews Endocrinology. 2015 Oct;11(10):592-605. doi: 10.1038/nrendo.2015.122. Epub 2015 Aug 11. PMID: 26260145; PMCID: PMC4578711.
Hotamisligil GS. Foundations of Immunometabolism and Implications for Metabolic Health and Disease. Immunity. 2017 Sep 19;47(3):406-420. doi: 10.1016/j.immuni.2017.08.009. PMID: 28930657; PMCID: PMC5627521.
Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature. 2017 Feb 8;542(7640):177-185. doi: 10.1038/nature21363. PMID: 28179656.