Author(s): Inouye KE, Prentice KJ, Lee A, Wang ZB, Dominguez-Gonzalez C, Chen MX, Riveros JK, Burak MF, Lee GY, Hotamisligil GS|Journal: JCI Insight|PMID:37279064| July 2023
Fatty acid binding protein 4 (FABP4) is a lipid chaperone secreted from adipocytes upon stimulation of lipolysis. Circulating FABP4 levels…
Author(s): Parlakgül G, Arruda AP, Pang S, Cagampan E, Min N, Güney E, Lee GY, Inouye K, Hess HF, Xu CS, Hotamisligil GS|Journal: Nature|PMID:35264794| March 2022
Cells display complex intracellular organization by compartmentalization of metabolic processes into organelles, yet the resolution of these structures in the…
Author(s): Güney E, Arruda AP, Parlakgül G, Cagampan E, Min N, Lee GY, Greene L, Tsaousidou E, Inouye K, Han MS, Davis RJ, Hotamisligil GS|Journal: Sci Signal|PMID:34905386| December 2021
Chronic metabolic inflammation is a key feature of obesity, insulin resistance, and diabetes. Here, we showed that altered regulation of…
Author(s): Prentice KJ, Saksi J, Robertson LT, Lee GY, Inouye KE, Eguchi K, Lee A, Cakici O, Otterbeck E, Cedillo P, Achenbach P, Ziegler AG, Calay ES, Engin F, Hotamisligil GS|Journal: Nature|PMID:34880500| December 2021
The liberation of energy stores from adipocytes is critical to support survival in times of energy deficit; however, uncontrolled or…
Author(s): Tirosh A, Tuncman G, Calay ES, Rathaus M, Ron I, Yalcin A, Lee YG, Livne R, Ron S, Minsky N, Arruda AP, Hotamisligil GS|Journal: Cell Metab|PMID:33340456| December 2020
Endoplasmic reticulum stress (ERS) has a pathophysiological role in obesity-associated insulin resistance. Yet, the coordinated tissue response to ERS remains…
Author(s): Zhang Z, Qian Q, Li M, Shao F, Ding WX, Lira VA, Chen SX, Sebag SC, Hotamisligil GS, Cao H, Yang L.|Journal: Autophagy|PMID:32597296| July 2020
Defective macroautophagy/autophagy and a failure to initiate the adaptive unfolded protein response (UPR) in response to the endoplasmic reticulum (ER)…
Author(s): Liu CL, Ren J, Wang Y, Zhang X, Sukhova GK, Liao M, Santos M, Luo S, Yang D, Xia M, Inouye K, Hotamisligil GS, Lu G, Upchurch GR, Libby P, Guo J, Zhang J, Shi GP|Journal: Eur Heart J|PMID:31821481| July 2020
Obesity is a risk factor of abdominal aortic aneurysm (AAA). Inflammatory cytokine interleukin-18 (IL18) has two receptors: IL18 receptor (IL18r)…
Author(s): Goncalves RLS, Hotamisligil GS|Journal: Cell Metab|PMID:31801059| December 2019
Cells utilize multiple mechanisms to support endoplasmic reticulum (ER) function. The unfolded protein response, UPR, is engaged during proteotoxic challenges…
Author(s): Leiria LO, Wang CH, Lynes MD, Yang K, Shamsi F, Sato M, Sugimoto S, Chen EY, Bussberg V, Narain NR, Sansbury BE, Darcy J, Huang TL, Kodani SD, Sakaguchi M, Rocha AL, Schulz TJ, Bartelt A, Hotamisligil GS, Hirshman MF, van Leyen K, Goodyear LJ, Blüher M, Cypess AM, Kiebish MA, Spite M, Tseng YH|Journal: Cell Metab|PMID:31353262| October 2019
Distinct oxygenases and their oxylipin products have been shown to participate in thermogenesis by mediating physiological adaptations required to sustain…
Author(s): 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|Journal: Sci Transl Med|PMID:31019023| April 2019
The short-chain fatty acid propionate is a potent inhibitor of molds that is widely used as a food preservative and…
Author(s): Liu L, Inouye KE, Allman WR, Coleman AS, Siddiqui S, Hotamisligil GS, Akkoyunlu M|Journal: Diabetes|PMID:29871859| August 2018
Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) is a receptor for the TNF superfamily cytokines, B cell-activating…
Author(s): Arruda AP, Pers BM, Parlakgül G, Güney E, Goh T, Cagampan E, Lee GY, Goncalves RL, Hotamisligil GS|Journal: Elife|PMID:29243589| December 2017
Defective Ca handling is a key mechanism underlying hepatic endoplasmic reticulum (ER) dysfunction in obesity. ER Ca level is in…
Author(s): Widenmaier SB, Snyder NA, Nguyen TB, Arduini A, Lee GY, Arruda AP, Saksi J, Bartelt A, Hotamisligil GS|Journal: Cell|PMID:29149604| November 2017
Cholesterol is a critical nutrient requiring tight constraint in the endoplasmic reticulum (ER) due to its uniquely challenging biophysical properties. While…
Author(s): Hotamisligil GS|Journal: Immunity|PMID:28930657| September 2017
Highly ordered interactions between immune and metabolic responses are evolutionarily conserved and paramount for tissue and organismal health. Disruption of…
Author(s): Parlakgül G, Hotamisligil GS|Journal: Cell Metab|PMID:28591628| June 2017
The specific immunological components linking metabolic stresses to liver inflammation and systemic metabolic pathologies in obesity are not entirely known.…
Author(s): Pan Y, Tian T, Park CO, Lofftus SY, Mei S, Liu X, Luo C, O'Malley JT, Gehad A, Teague JE, Divito SJ, Fuhlbrigge R, Puigserver P, Krueger JG, Hotamisligil GS, Clark RA, Kupper TS|Journal: Nature|PMID:28219080| March 2017
Tissue-resident memory T (T) cells persist indefinitely in epithelial barrier tissues and protect the host against pathogens. However, the biological…
Author(s): Hotamisligil GS|Journal: Nature|PMID:28179656| February 2017
Proper regulation and management of energy, substrate diversity and quantity, as well as macromolecular synthesis and breakdown processes, are fundamental…
Author(s): Babaev VR, Yeung M, Erbay E, Ding L, Zhang Y, May JM, Fazio S, Hotamisligil GS, Linton MF|Journal: Arterioscler Thromb Vasc Biol|PMID:27102962| June 2016
The c-Jun NH2-terminal kinases (JNK) are regulated by a wide variety of cellular stresses and have been implicated in apoptotic…
Author(s): 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|Journal: Sci Transl Med|PMID:26702093| December 2015
The lipid chaperone aP2/FABP4 has been implicated in the pathology of many immunometabolic diseases, including diabetes in humans, but aP2…
Author(s): Hotamisligil GS, Bernlohr DA|Journal: Nat Rev Endocrinol|PMID:26260145| October 2015
Intracellular and extracellular interactions with proteins enables the functional and mechanistic diversity of lipids. Fatty acid-binding proteins (FABPs) were originally…
Author(s): Brozzi F, Nardelli TR, Lopes M, Millard I, Barthson J, Igoillo-Esteve M, Grieco FA, Villate O, Oliveira JM, Casimir M, Bugliani M, Engin F, Hotamisligil GS, Marchetti P, Eizirik DL|Journal: Diabetologia|PMID:26099855| October 2015
Proinflammatory cytokines contribute to beta cell damage in type 1 diabetes in part through activation of endoplasmic reticulum (ER) stress.…
Author(s): Arruda AP, Hotamisligil GS|Journal: Cell Metab|PMID:26190652| September 2015
A number of chronic metabolic pathologies, including obesity, diabetes, cardiovascular disease, asthma, and cancer, cluster together to present the greatest…
Author(s): Fu S, Yalcin A, Lee GY, Li P, Fan J, Arruda AP, Pers BM, Yilmaz M, Eguchi K, Hotamisligil GS|Journal: Sci Transl Med|PMID:26084805| June 2015
The endoplasmic reticulum (ER) plays a critical role in protein, lipid, and glucose metabolism as well as cellular calcium signaling…
Aberrant stress and inflammatory responses are key factors in the pathogenesis of obesity and metabolic dysfunction, and the double-stranded RNA-dependent…
Author(s): Zhang Y, Nicholatos J, Dreier JR, Ricoult SJ, Widenmaier SB, Hotamisligil GS, Kwiatkowski DJ, Manning BD|Journal: Nature|PMID:25043031| September 2014
Eukaryotic cells coordinately control anabolic and catabolic processes to maintain cell and tissue homeostasis. Mechanistic target of rapamycin complex 1…
Author(s): Syamsunarno MR, Iso T, Hanaoka H, Yamaguchi A, Obokata M, Koitabashi N, Goto K, Hishiki T, Nagahata Y, Matsui H, Sano M, Kobayashi M, Kikuchi O, Sasaki T, Maeda K, Murakami M, Kitamura T, Suematsu M, Tsushima Y, Endo K, Hotamisligil GS, Kurabayashi M|Journal: PLoS One|PMID:24244493| November 2013
During prolonged fasting, fatty acid (FA) released from adipose tissue is a major energy source for peripheral tissues, including the…
Author(s): Engin F, Yermalovich A, Nguyen T, Hummasti S, Fu W, Eizirik DL, Mathis D, Hotamisligil GS|Journal: Sci Transl Med|PMID:24225943| November 2013
Perturbations in endoplasmic reticulum (ER) homeostasis can evoke stress responses leading to aberrant glucose and lipid metabolism. ER dysfunction is…
Author(s): Liu S, Brown JD, Stanya KJ, Homan E, Leidl M, Inouye K, Bhargava P, Gangl MR, Dai L, Hatano B, Hotamisligil GS, Saghatelian A, Plutzky J, Lee CH|Journal: Nature|PMID:24153306| October 2013
Food intake increases the activity of hepatic de novo lipogenesis, which mediates the conversion of glucose to fats for storage…
Author(s): Gregor MF, Misch ES, Yang L., Hummasti S, Inouye KE, Lee AH, Bierie B, Hotamisligil GS|Journal: Cell Rep|PMID:23623498| May 2013
The adipocyte is central to organismal metabolism and exhibits significant functional and morphological plasticity during its formation and lifespan. Remarkable…
Author(s): Cao H, Sekiya M, Ertunc ME, Burak MF, Mayers JR, White A, Inouye K, Rickey LM, Ercal BC, Furuhashi M, Tuncman G, Hotamisligil GS|Journal: Cell Metab|PMID:23663740| May 2013
Proper control of hepatic glucose production is central to whole-body glucose homeostasis, and its disruption plays a major role in…
Author(s): Ghelfi E, Yu CW, Elmasri H, Terwelp M, Lee CG, Bhandari V, Comhair SA, Erzurum SC, Hotamisligil GS, Elias JA, Cataltepe S|Journal: Am J Pathol|PMID:23391391| April 2013
Neovascularization of the airways occurs in several inflammatory lung diseases, including asthma. Vascular endothelial growth factor (VEGF) plays an important…
Author(s): Lu B, Nakamura T, Inouye K, Li J, Tang Y, Lundbäck P, Valdes-Ferrer SI, Olofsson PS, Kalb T, Roth J, Zou Y, Erlandsson-Harris H, Yang H, Ting JP, Wang H, Andersson U, Antoine DJ, Chavan SS, Hotamisligil GS, Tracey KJ|Journal: Nature|PMID:22801494| August 2012
The inflammasome regulates the release of caspase activation-dependent cytokines, including interleukin (IL)-1β, IL-18 and high-mobility group box 1 (HMGB1). By…
Author(s): Fu S, Fan J, Blanco J, Gimenez-Cassina A, Danial NN, Watkins SM, Hotamisligil GS|Journal: PLoS Genet|PMID:22927828| August 2012
Obesity-associated metabolic complications are generally considered to emerge from abnormalities in carbohydrate and lipid metabolism, whereas the status of protein…
Author(s): Fukuda D, Aikawa E, Swirski FK, Novobrantseva TI, Kotelianski V, Gorgun CZ, Chudnovskiy A, Yamazaki H, Croce K, Weissleder R, Aster JC, Hotamisligil GS, Yagita H, Aikawa M|Journal: Proc Natl Acad Sci U S A|PMID:22699504| July 2012
Atherosclerosis and insulin resistance are major components of the cardiometabolic syndrome, a global health threat associated with a systemic inflammatory…
Author(s): Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, Romero IL, Carey MS, Mills GB, Hotamisligil GS, Yamada SD, Peter ME, Gwin K, Lengyel E|Journal: Nat Med|PMID:22037646| October 2011
Intra-abdominal tumors, such as ovarian cancer, have a clear predilection for metastasis to the omentum, an organ primarily composed of…
Author(s): Yecies JL, Zhang HH, Menon S, Liu S, Yecies D, Lipovsky AI, Gorgun C, Kwiatkowski DJ, Hotamisligil GS, Lee CH, Manning BD|Journal: Cell Metab|PMID:21723501| July 2011
Through unknown mechanisms, insulin activates the sterol regulatory element-binding protein (SREBP1c) transcription factor to promote hepatic lipogenesis. We find that…
Author(s): Babaev VR, Runner RP, Fan D, Ding L, Zhang Y, Tao H, Erbay E, Gorgun CZ, Fazio S, Hotamisligil GS, Linton MF|Journal: Arterioscler Thromb Vasc Biol|PMID:21474828| June 2011
The adipocyte/macrophage fatty acid-binding proteins aP2 (FABP4) and Mal1 (FABP5) are intracellular lipid chaperones that modulate systemic glucose metabolism, insulin…
Author(s): Furuhashi M, Ishimura S, Ota H, Hayashi M, Nishitani T, Tanaka M, Yoshida H, Shimamoto K, Hotamisligil GS, Miura T|Journal: PLoS One|PMID:22102888| January 2011
Fatty acid-binding protein 4 (FABP4/A-FABP/aP2), a lipid chaperone, is expressed in both adipocytes and macrophages. Recent studies have shown that…
Author(s): Mozaffarian D, Cao H, King IB, Lemaitre RN, Song X, Siscovick DS, Hotamisligil GS|Journal: Am J Clin Nutr|PMID:20943795| December 2010
Animal experiments suggest that circulating palmitoleic acid (cis-16:1n-7) from adipocyte de novo fatty acid synthesis may directly regulate insulin resistance…
Author(s): Engin F, Hotamisligil GS|Journal: Diabetes Obes Metab|PMID:21029307| October 2010
The endoplasmic reticulum (ER) is a eukaryotic organelle that plays important roles in protein synthesis, folding and trafficking, calcium homoeostasis…
Author(s): Kars M, Yang L., Gregor MF, Mohammed BS, Pietka TA, Finck BN, Patterson BW, Horton JD, Mittendorfer B, Hotamisligil GS, Klein S|Journal: Diabetes|PMID:20522594| August 2010
Insulin resistance is commonly associated with obesity. Studies conducted in obese mouse models found that endoplasmic reticulum (ER) stress contributes…
Author(s): Hotamisligil GS|Journal: Nat Med|PMID:20376052| April 2010
Atherosclerosis and related cardiovascular diseases represent one of the greatest threats to human health worldwide. Despite important progress in prevention…
Author(s): Erbay E, Babaev VR, Mayers JR, Makowski L, Charles KN, Snitow ME, Fazio S, Wiest MM, Watkins SM, Linton MF, Hotamisligil GS|Journal: Nat Med|PMID:19966778| December 2009
Macrophages show endoplasmic reticulum (ER) stress when exposed to lipotoxic signals associated with atherosclerosis, although the pathophysiological importance and the…
Author(s): Gregor MF, Yang L., Fabbrini E, Mohammed BS, Eagon JC, Hotamisligil GS, Klein S|Journal: Diabetes|PMID:19066313| March 2009
Obesity is associated with insulin resistance and type 2 diabetes, although the mechanisms linking these pathologies remain undetermined. Recent studies…
Author(s): Hotamisligil GS|Journal: Int J Obes (Lond)|PMID:19136991| December 2008
Obesity is associated with chronic low-grade inflammation. Inflammatory signals interfere with insulin action and disrupt metabolic homeostasis. The c-Jun N-terminal…
Author(s): Cao H, Gerhold K, Mayers JR, Wiest MM, Watkins SM, Hotamisligil GS|Journal: Cell|PMID:18805087| September 2008
Dysregulation of lipid metabolism in individual tissues leads to systemic disruption of insulin action and glucose metabolism. Utilizing quantitative lipidomic…
Author(s): Furuhashi M, Fucho R, Gorgun CZ, Tuncman G, Cao H, Hotamisligil GS|Journal: J Clin Invest|PMID:18551191| July 2008
Adipose tissue inflammation is a characteristic of obesity. However, the mechanisms that regulate this inflammatory response and link adipose inflammation…