Representative Publications

Uysal KT, Wiesbrock SM, Marino MW, Hotamışlıgil GS. Protection from obesity-induced insulin resistance in mice lacking TNF-a.  Nature. 1997, 389:610-614.

Hirosumi J, Tuncman G, Chang L, Gorgun C, Uysal T, Maeda K, Karin M, Hotamışlıgil GS. A central role for JNK in obesity and insulin resistance.  Nature. 2002, 420:333-336.

Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tunçman G, Glimcher L, Hotamışlıgil GS. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes.  Science. 2004, 306:457-461.

Wellen K, Fucho R, Gregor MF, Furuhashi M, Morgan C, Lindstad T, Vaillancourt E, Gorgun CZ, Saatcioglu F, Hotamışlıgil GS. Coordinated regulation of nutrient and inflammatory responses by Stamp2 is essential for metabolic homeostasis. Cell. 2007, 129:537-548.

Cao H, Gerhold K, Wiest MW, Watkins SM, Hotamışlıgil GS. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell. 2008, 134:933-944.

Erbay E, Babaev VR, Mayers JR, Makowski L, Charles KN, Snitow M, Fazio S, Wiest MM, Watkins SM, Linton MF, Hotamışlıgil GS. Reducing endoplasmic reticulum stress through a macrophage lipid chaperone alleviates atherosclerosis. Nature Medicine. 2009, 12:1383-91.

Nakamura T, Furuhashi M, Li P, Cao H, Tunçman G, Sonenberg N, Gorgun CZ, Hotamışlıgil GS. Double-stranded RNA-dependent protein kinase links pathogen sensing with stress and metabolic homeostasis. Cell. 2010, 140:338-348.

Yang L, Li P, Fu S, Calay ES, Hotamışlıgil GS. Defective hepatic autophagy in obesity causes insulin resistance. Cell Metabolism. 2010, 11:467-478.

Fu S, Yang L, Li P, Hoffman O, Dicker L, Hide W, Lin X, Watkins, SM, Ivanov A, Hotamışlıgil GS. Aberrant lipid metabolism disrupts calcium homeostasis causing liver ER stress in obesity. Nature. 2012, 473; 528-531.

Cao H, Sekiya M, Ertunc ME, Burak MF, Mayers JR, White A, Inouye K, Rickey LM, Ercal BC, Furuhashi M, Tuncman G, Hotamışlıgil GS. Adipocyte lipid chaperone AP2 is a secreted adipokine regulating hepatic glucose production. Cell Metabolism. 2013, 17:768-78.

Arruda AP, Pers BM, Parlakgül G, Güney E, Inouye K, Hotamışlıgil GS. Chronic enrichment of hepatic endoplasmic reticulum—mitochondria contact leads to mitochondrial dysfunction in obesity. Nature Medicine. 2014, 20(12):1427-35.

Yang L, Calay E, Fan J, Arduini A, Kunz RC, Gygi SP, Yalcin A, Fu S, Hotamışlıgil GS. S-Nitrosylation links obesity-associated inflammation to endoplasmic reticulum dysfunction. Science. 2015 Jul 31;349(6247):500-6.

Widenmaier SB, Arduini A, Snyder N, Nguyen T, Lee G, Arruda AP, Bartelt A, Hotamışlıgil GS. Nrf1 is an ER membrane sensor that is central to cholesterol homeostasis.  Cell. 2017 Nov 16;171(5):1094-1109.e15.

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, Hotamışlıgil GS. Brown adipose tissue thermogenic adaptation requires Nrf1-mediated proteasomal activity. Nature Medicine. 2018 Mar;24(3):292-303. doi: 10.1038/nm.4481.

Tirosh A, Tuncman G, Calay ES, Rathaus M, Ron I, Tirosh A, Yalcin A, Lee YG, Livne R, Ron S, Minsky N, Arruda AP, Hotamışlıgil GS. Inter-cellular transmission of hepatic ER stress in obesity disrupts systemic metabolism. Cell Metabolism. 2020 Dec 9:S1550-4131(20)30604-5. doi: 10.1016/j.cmet.2020.11.009

Translational Studies:

Furuhashi M, Tunçman G, Gorgun CZ, Makowski L, Atsumi G, Vaillancourt E, Kono K, Babaev VR, Fazio S, Linton MF, Sulsky R, Robl JA, Parker RA, Hotamışlıgil GS. Treatment of diabetes and atherosclerosis by inhibiting fatty acid-binding protein aP2/FABP4. Nature. 2007, 447:959-965.

Mozaffarian D, Cao H, King IB, Lemaitre RN, Song X, Siscovick DS, Hotamışlıgil GS. Trans-palmitoleic acid, metabolic risk factors, and new-onset diabetes in US adults. Ann Intern Med. 2010, 153:790-9.

Engin F, Yermalovich A, Nguyen T, Hummasti S, Fu W, Eizirik DL, Mathis D, Hotamışlıgil GS. Restoration of the unfolded protein response in pancreatic β cells protects mice against type 1 diabetes. Science Translational Medicine. 2013, 13;5(211).

Fu S, Yalcin A, Lee GY, Li P, Fan J, Arruda AP, Pers BM, Yilmaz M, Eguchi K, Hotamışlıgil 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.

Burak FM, Inouye K, 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, Hotamışlıgil GS. Development of a therapeutic monoclonal antibody that targets secreted fatty acid-binding protein FABP4 to treat type 2 diabetes. Science Translational Medicine. 2015 Dec 23;7(319):319ra205. doi: 10.1126/scitranslmed.aac6336.

Tirosh, A, Calay ES, Tunçman G, Claiborn K, Eguchi K, Alcala M, Rathaus M, Hollander K, Ron I, Garg R, Hotamışlıgil 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). pii: eaav0120. doi: 10.1126/scitranslmed.aav0120.

Reviews and Commentaries:

Hotamışlıgil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 2010, 140:900-917.

Fu S, Watkins SM, Hotamışlıgil GS. The role of endoplasmic reticulum in hepatic lipid homeostasis and stress signaling. Cell Metabolism. 2012, 15:623-34.

Arruda A, Hotamışlıgil 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.

Hotamışlıgil 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.

Hotamışlıgil GS. The foundations of immunometabolism: implications for health and disease. Immunity. 2017, 47:406-420. doi: 10.1016/j.immuni.2017.08.009

Hotamışlıgil GS. Inflammation, metaflammation and immunometabolic disorders. Nature. 2017 Feb 8;542(7640):177-185. doi: 10.1038/nature21363