1,825
Views
13
CrossRef citations to date
0
Altmetric
Research Paper

Glucose starvation and hypoxia, but not the saturated fatty acid palmitic acid or cholesterol, activate the unfolded protein response in 3T3-F442A and 3T3-L1 adipocytes

&
Pages 188-202 | Received 05 Jun 2014, Accepted 14 Nov 2014, Published online: 12 Jan 2015

References

  • Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006; 444:860-7; PMID:17167474; http://dx.doi.org/10.1038/nature05485
  • Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature 2006; 444:875-80; PMID:17167476; http://dx.doi.org/10.1038/nature05487
  • Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Invest 2011; 121:2094-101; PMID:21633177; http://dx.doi.org/10.1172/JCI45887
  • Ye J, Gao Z, Yin J, He Q. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab 2007; 293: E1118-28; PMID:17666485; http://dx.doi.org/10.1152/ajpendo.00435.2007
  • Coenen KR, Gruen ML, Chait A, Hasty AH. Diet-induced increases in adiposity, but not plasma lipids, promote macrophage infiltration into white adipose tissue. Diabetes 2007; 56:564-73; PMID:17327423; http://dx.doi.org/10.2337/db06-1375
  • Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 2007; 117:175-84; PMID:17200717; http://dx.doi.org/10.1172/JCI29881
  • Schröder M. Endoplasmic reticulum stress responses. Cell Mol Life Sci 2008; 65:862-94; PMID:18038217; http://dx.doi.org/10.1007/s00018-007-7383-5
  • Zhang K, Kaufman RJ. From endoplasmic-reticulum stress to the inflammatory response. Nature 2008; 454:455-62; PMID:18650916; http://dx.doi.org/10.1038/nature07203
  • Samuel VT, Shulman GI. Mechanisms for insulin resistance: common threads and missing links. Cell 2012; 148:852-71; PMID:22385956; http://dx.doi.org/10.1016/j.cell.2012.02.017
  • Gregor MF, Hotamisligil GS. Adipocyte stress: the endoplasmic reticulum and metabolic disease. J Lipid Res 2007; 48:1905-14; PMID:17699733; http://dx.doi.org/10.1194/jlr.R700007-JLR200
  • Schröder M, Kaufman RJ. ER stress and the unfolded protein response. Mutat Res 2005; 569:29-63; PMID:15603751; http://dx.doi.org/10.1016/j.mrfmmm.2004.06.056
  • Marciniak SJ, Yun CY, Oyadomari S, Novoa I, Zhang Y, Jungreis R, Nagata K, Harding HP, Ron D. CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev 2004; 18:3066-77; PMID:15601821; http://dx.doi.org/10.1101/gad.1250704
  • Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, Harding HP, Clark SG, Ron D. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 2002; 415:92-6; PMID:11780124; http://dx.doi.org/10.1038/415092a
  • Yoshida H, Matsui T, Yamamoto A, Okada T, Mori K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 2001; 107:881-91; PMID:11779464; http://dx.doi.org/10.1016/S0092-8674(01)00611-0
  • Ye J, Rawson RB, Komuro R, Chen X, Dave UP, Prywes R, Brown MS, Goldstein JL. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol Cell 2000; 6:1355-64; PMID:11163209; http://dx.doi.org/10.1016/S1097-2765(00)00133-7
  • Wu J, Rutkowski DT, Dubois M, Swathirajan J, Saunders T, Wang J, Song B, Yau GD-Y, Kaufman RJ. ATF6α optimizes long-term endoplasmic reticulum function to protect cells from chronic stress. Dev Cell 2007; 13:351-64; PMID:17765679; http://dx.doi.org/10.1016/j.devcel.2007.07.005
  • Yamamoto K, Sato T, Matsui T, Sato M, Okada T, Yoshida H, Harada A, Mori K. Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6α and XBP1. Dev Cell 2007; 13:365-76; PMID:17765680; http://dx.doi.org/10.1016/j.devcel.2007.07.018
  • Nishitoh H, Matsuzawa A, Tobiume K, Saegusa K, Takeda K, Inoue K, Hori S, Kakizuka A, Ichijo H. ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev 2002; 16:1345-55; PMID:12050113; http://dx.doi.org/10.1101/gad.992302
  • Ohoka N, Yoshii S, Hattori T, Onozaki K, Hayashi H. TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death. EMBO J 2005; 24:1243-55; PMID:15775988; http://dx.doi.org/10.1038/sj.emboj.7600596
  • Özcan U, Cao Q, Yilmaz E, Lee A-H, 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; 306:457-61; PMID:15486293; http://dx.doi.org/10.1126/science.1103160
  • Wei Y, Wang D, Topczewski F, Pagliassotti MJ. Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells. Am J Physiol Endocrinol Metab 2006; 291:E275-81; PMID:16492686; http://dx.doi.org/10.1152/ajpendo.00644.2005
  • Laybutt DR, Preston AM, Åkerfeldt MC, Kench JG, Busch AK, Biankin AV, Biden TJ. Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes. Diabetologia 2007; 50:752-63; PMID:17268797; http://dx.doi.org/10.1007/s00125-006-0590-z
  • DeVries-Seimon T, Li Y, Yao PM, Stone E, Wang Y, Davis RJ, Flavell R, Tabas I. Cholesterol-induced macrophage apoptosis requires ER stress pathways and engagement of the type A scavenger receptor. J Cell Biol 2005; 171:61-73; PMID:16203857; http://dx.doi.org/10.1083/jcb.200502078
  • Guo W, Wong S, Xie W, Lei T, Luo Z. Palmitate modulates intracellular signaling, induces endoplasmic reticulum stress, and causes apoptosis in mouse 3T3-L1 and rat primary preadipocytes. Am J Physiol Endocrinol Metab 2007; 293:E576-86; PMID:17519282; http://dx.doi.org/10.1152/ajpendo.00523.2006
  • Antuna-Puente B, Feve B, Fellahi S, Bastard J-P. Adipokines: the missing link between insulin resistance and obesity. Diabetes Metab 2008; 34:2-11; PMID:18093861; http://dx.doi.org/10.1016/j.diabet.2007.09.004
  • Zhang K, Shen X, Wu J, Sakaki K, Saunders T, Rutkowski DT, Back SH, Kaufman RJ. Endoplasmic reticulum stress activates cleavage of CREBH to induce a systemic inflammatory response. Cell 2006; 124:587-99; PMID:16469704; http://dx.doi.org/10.1016/j.cell.2005.11.040
  • Xue X, Piao J-H, Nakajima A, Sakon-Komazawa S, Kojima Y, Mori K, Yagita H, Okumura K, Harding H, Nakano H. Tumor necrosis factor α (TNFα) induces the unfolded protein response (UPR) in a reactive oxygen species (ROS)-dependent fashion, and the UPR counteracts ROS accumulation by TNFα. J Biol Chem 2005; 280:33917-25; PMID:16107336; http://dx.doi.org/10.1074/jbc.M505818200
  • Shiu RP, Pouyssegur J, Pastan I. Glucose depletion accounts for the induction of two transformation-sensitive membrane proteins in Rous sarcoma virus-transformed chick embryo fibroblasts. Proc Natl Acad Sci U S A 1977; 74:3840-4; PMID:198809; http://dx.doi.org/10.1073/pnas.74.9.3840
  • Lin AY, Lee AS. Induction of two genes by glucose starvation in hamster fibroblasts. Proc Natl Acad Sci U S A 1984; 81:988-92; PMID:6583707; http://dx.doi.org/10.1073/pnas.81.4.988
  • Romero-Ramirez L, Cao H, Nelson D, Hammond E, Lee A-H, Yoshida H, Mori K, Glimcher LH, Denko NC, Giaccia AJ, et al. XBP1 is essential for survival under hypoxic conditions and is required for tumor growth. Cancer Res 2004; 64:5943-7; PMID:15342372; http://dx.doi.org/10.1158/0008-5472.CAN-04-1606
  • Koumenis C, Naczki C, Koritzinsky M, Rastani S, Diehl A, Sonenberg N, Koromilas A, Wouters BG. Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2α. Mol Cell Biol 2002; 22:7405-16; PMID:12370288; http://dx.doi.org/10.1128/MCB.22.21.7405-7416.2002
  • Bi MX, Naczki C, Koritzinsky M, Fels D, Blais J, Hu NP, Harding H, Novoa I, Varia M, Raleigh J, et al. ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth. EMBO J 2005; 24:3470-81; PMID:16148948; http://dx.doi.org/10.1038/sj.emboj.7600777
  • Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor-α in human obesity and insulin resistance. J Clin Invest 1995; 95:2409-15; PMID:7738205; http://dx.doi.org/10.1172/JCI117936
  • Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 2001; 280:E745-51; PMID:11287357
  • Misaki Y, Miyauchi R, Mochizuki K, Takabe S, Shimada M, Ichikawa Y, Goda T. Plasma interleukin-1β concentrations are closely associated with fasting blood glucose levels in healthy and preclinical middle-aged nonoverweight and overweight Japanese men. Metabolism 2010; 59:1465-71; PMID:20170929; http://dx.doi.org/10.1016/j.metabol.2010.01.011
  • Spranger J, Kroke A, Möhlig M, Hoffmann K, Bergmann MM, Ristow M, Boeing H, Pfeiffer AFH. Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 2003; 52:812-7; PMID:12606524; http://dx.doi.org/10.2337/diabetes.52.3.812
  • Tremblay AJ, Després JP, Piché ME, Nadeau A, Bergeron J, Alméras N, Tremblay A, Lemieux S. Associations between the fatty acid content of triglyceride, visceral adipose tissue accumulation, and components of the insulin resistance syndrome. Metabolism 2004; 53:310-7; PMID:15015142; http://dx.doi.org/10.1016/j.metabol.2003.10.011
  • Sorensen TI, Andersen B, Kam-Hansen L. Total plasma cholesterol in obesity after jejunoileal bypass with 3:1 or 1:3 jejunoileal ratio. A randomized trial. Scand J Gastroenterol 1979; 14:865-8; PMID:395631; http://dx.doi.org/10.3109/00365527909181417
  • Dobrea GM, Wieland RG, Johnson MW. The effect of rapid weight loss due to jejunoileal bypass on total cholesterol and high-density lipoprotein. Am J Clin Nutr 1981; 34:1994-6; PMID:7293931
  • Green H, Kehinde O. Formation of normally differentiated subcutaneous fat pads by an established preadipose cell line. J Cell Physiol 1979; 101:169-71; PMID:541350; http://dx.doi.org/10.1002/jcp.1041010119
  • Mandrup S, Loftus TM, MacDougald OA, Kuhajda FP, Lane MD. Obese gene expression at in vivo levels by fat pads derived from s.c. implanted 3T3-F442A preadipocytes. Proc Natl Acad Sci U S A 1997; 94:4300-5; PMID:9113984; http://dx.doi.org/10.1073/pnas.94.9.4300
  • Greenspan P, Mayer EP, Fowler SD. Nile red: a selective fluorescent stain for intracellular lipid droplets. J Cell Biol 1985; 100:965-73; PMID:3972906; http://dx.doi.org/10.1083/jcb.100.3.965
  • Crandall DL, Quinet EM, Morgan GA, Busler DE, McHendry-Rinde B, Kral JG. Synthesis and secretion of plasminogen activator inhibitor-1 by human preadipocytes. J Clin Endocrinol Metab 1999; 84:3222-7; PMID:10487691; http://dx.doi.org/10.1210/jcem.84.9.5987
  • Schaedlich K, Knelangen JM, Santos AN, Fischer B. A simple method to sort ESC-derived adipocytes. Cytometry A 2010; 77:990-5; PMID:21290474; http://dx.doi.org/10.1002/cyto.a.20953
  • Rubin CS, Hirsch A, Fung C, Rosen OM. Development of hormone receptors and hormonal responsiveness in vitro. Insulin receptors and insulin sensitivity in the preadipocyte and adipocyte forms of 3T3-L1 cells. J Biol Chem 1978; 253:7570-8; PMID:81205.
  • Lee YH, Chen SY, Wiesner RJ, Huang YF. Simple flow cytometric method used to assess lipid accumulation in fat cells. J Lipid Res 2004; 45:1162-7; PMID:14993237; http://dx.doi.org/10.1194/jlr.D300028-JLR200
  • Rothe G. Technical background and methodological principles of flow cytometry. In: Sack U, Tárnok A, Rothe G, eds. Cellular Diagnostics Basics, Methods and Clinical Applications of Flow Cytometry. Basel: Taylor & Francis, 2009:53-88.
  • Back SH, Schröder M, Lee K, Zhang K, Kaufman RJ. ER stress signaling by regulated splicing: IRE1/HAC1/XBP1. Methods 2005; 35:395-416; PMID:15804613; http://dx.doi.org/10.1016/j.ymeth.2005.03.001
  • Yang L, Qian Z, Ji H, Yang R, Wang Y, Xi L, Sheng L, Zhao B, Zhang X. Inhibitory effect on protein kinase Cθ by crocetin attenuates palmitate-induced insulin insensitivity in 3T3-L1 adipocytes. Eur J Pharmacol 2010; 642:47-55; PMID:20541543; http://dx.doi.org/10.1016/j.ejphar.2010.05.061
  • Dasgupta S, Bhattacharya S, Biswas A, Majumdar SS, Mukhopadhyay S, Ray S, Bhattacharya S. NF-κB mediates lipid-induced fetuin-A expression in hepatocytes that impairs adipocyte function effecting insulin resistance. Biochem J 2010; 429:451-62; PMID:20482516; http://dx.doi.org/10.1042/BJ20100330
  • Xi L, Qian Z, Xu G, Zhou C, Sun S. Crocetin attenuates palmitate-induced insulin insensitivity and disordered tumor necrosis factor-α and adiponectin expression in rat adipocytes. Br J Pharmacol 2007; 151:610-7; PMID:17471172; http://dx.doi.org/10.1038/sj.bjp.0707276
  • Chavez JA, Summers SA. Characterizing the effects of saturated fatty acids on insulin signaling and ceramide and diacylglycerol accumulation in 3T3-L1 adipocytes and C2C12 myotubes. Arch Biochem Biophys 2003; 419:101-9; PMID:14592453; http://dx.doi.org/10.1016/j.abb.2003.08.020
  • Usui I, Haruta T, Takata Y, Iwata M, Uno T, Takano A, Ueno E, Ishibashi O, Ishihara H, Wada T, et al. Differential effects of palmitate on glucose uptake in rat-1 fibroblasts and 3T3-L1 adipocytes. Horm Metab Res 1999; 31:546-52; PMID:10596963; http://dx.doi.org/10.1055/s-2007-978793
  • Hunnicutt JW, Hardy RW, Williford J, McDonald JM. Saturated fatty acid-induced insulin resistance in rat adipocytes. Diabetes 1994; 43:540-5; PMID:8138059; http://dx.doi.org/10.2337/diab.43.4.540
  • Van Epps-Fung M, Williford J, Wells A, Hardy RW. Fatty acid-induced insulin resistance in adipocytes. Endocrinology 1997; 138:4338-45; PMID:9322948
  • Lundgren M, Eriksson JW. No in vitro effects of fatty acids on glucose uptake, lipolysis or insulin signaling in rat adipocytes. Horm Metab Res 2004; 36:203-9; PMID:15114517; http://dx.doi.org/10.1055/s-2004-814446
  • Tao J-L, Ruan X-Z, Li H, Li X-M, Moorhead JF, Varghese Z, Li X-W. Endoplasmic reticulum stress is involved in acetylated low-density lipoprotein induced apoptosis in THP-1 differentiated macrophages. Chin Med J (Engl) 2009; 122:1794-9; PMID:19781328
  • Kasambalides EJ, Lanks KW. Effects of low molecular weight nutrients on the pattern of proteins synthesized by non-proliferating murine L cells. Exp Cell Res 1981; 132:31-9; PMID:7202562; http://dx.doi.org/10.1016/0014-4827(81)90079-3
  • Kowalchuk JM, Curi R, Newsholme EA. Glutamine metabolism in isolated incubated adipocytes of the rat. Biochem J 1988; 249:705-8; PMID:2895633
  • Yoo H, Antoniewicz MR, Stephanopoulos G, Kelleher JK. Quantifying reductive carboxylation flux of glutamine to lipid in a brown adipocyte cell line. J Biol Chem 2008; 283:20621-7; PMID:18364355; http://dx.doi.org/10.1074/jbc.M706494200
  • Semenza GL. HIF-1: mediator of physiological and pathophysiological responses to hypoxia. J Appl Physiol 2000; 88:1474-80; PMID:10749844
  • Kallinowski F, Runkel S, Fortmeyer HP, Förster H, Vaupel P. L-glutamine: a major substrate for tumor cells in vivo? J Cancer Res Clin Oncol 1987; 113:209-15; PMID:3584211; http://dx.doi.org/10.1007/BF00396375
  • Chandramouli V, Carter JR Jr. Metabolic effects of 2-deoxy-D-glucose in isolated fat cells. Biochim Biophys Acta 1977; 496:278-91; PMID:836900; http://dx.doi.org/10.1016/0304-4165(77)90310-5
  • Skurk T, Alberti-Huber C, Herder C, Hauner H. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab 2007; 92:1023-33; PMID:17164304; http://dx.doi.org/10.1210/jc.2006-1055
  • Yin J, Gao Z, He Q, Zhou D, Guo Z, Ye J. Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue. Am J Physiol Endocrinol Metab 2009; 296:E333-42; PMID:19066318; http://dx.doi.org/10.1152/ajpendo.90760.2008
  • Hosogai N, Fukuhara A, Oshima K, Miyata Y, Tanaka S, Segawa K, Furukawa S, Tochino Y, Komuro R, Matsuda M, et al. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 2007; 56:901-11; PMID:17395738; http://dx.doi.org/10.2337/db06-0911
  • Michailidou Z, Turban S, Miller E, Zou X, Schrader J, Ratcliffe PJ, Hadoke PW, Walker BR, Iredale JP, Morton NM, et al. Increased angiogenesis protects against adipose hypoxia and fibrosis in metabolic disease-resistant 11β-hydroxysteroid dehydrogenase type 1 (HSD1)-deficient mice. J Biol Chem 2012; 287:4188-97; PMID:22158867; http://dx.doi.org/10.1074/jbc.M111.259325
  • Sung H-K, Doh K-O, Son JE, Park JG, Bae Y, Choi S, Nelson SM, Cowling R, Nagy K, Michael IP, et al. Adipose vascular endothelial growth factor regulates metabolic homeostasis through angiogenesis. Cell Metab 2013; 17:61-72; PMID:23312284; http://dx.doi.org/10.1016/j.cmet.2012.12.010
  • Sun K, Wernstedt Asterholm I, Kusminski CM, Bueno AC, Wang ZV, Pollard JW, Brekken RA, Scherer PE. Dichotomous effects of VEGF-A on adipose tissue dysfunction. Proc Natl Acad Sci U S A 2012; 109:5874-9; PMID:22451920; http://dx.doi.org/10.1073/pnas.1200447109
  • Cornelius P, MacDougald OA, Lane MD. Regulation of adipocyte development. Annu Rev Nutr 1994; 14:99-129; PMID:7946535; http://dx.doi.org/10.1146/annurev.nu.14.070194.000531
  • Gregoire FM, Smas CM, Sul HS. Understanding adipocyte differentiation. Physiol Rev 1998; 78:783-809; PMID:9674695
  • Bosma M, Dapito DH, Drosatos-Tampakaki Z, Huiping-Son N, Huang L-S, Kersten S, Drosatos K, Goldberg IJ. Sequestration of fatty acids in triglycerides prevents endoplasmic reticulum stress in an in vitro model of cardiomyocyte lipotoxicity. Biochim Biophys Acta 2014; 1841:1648-55; PMID:25251292; http://dx.doi.org/10.1016/j.bbalip.2014.09.012
  • Kovanen PT, Nikkilä EA, Miettinen TA. Regulation of cholesterol synthesis and storage in fat cells. J Lipid Res 1975; 16:211-23; PMID:1127358
  • Prattes S, Hörl G, Hammer A, Blaschitz A, Graier WF, Sattler W, Zechner R, Steyrer E. Intracellular distribution and mobilization of unesterified cholesterol in adipocytes: triglyceride droplets are surrounded by cholesterol-rich ER-like surface layer structures. J Cell Sci 2000; 113:2977-89; PMID:10934037
  • Ross SE, Erickson RL, Gerin I, DeRose PM, Bajnok L, Longo KA, Misek DE, Kuick R, Hanash SM, Atkins KB, et al. Microarray analyses during adipogenesis: understanding the effects of Wnt signaling on adipogenesis and the roles of liver X receptor a in adipocyte metabolism. Mol Cell Biol 2002; 22:5989-99; PMID:12138207; http://dx.doi.org/10.1128/MCB.22.16.5989-5999.2002
  • Burton GR, Nagarajan R, Peterson CA, McGehee RE Jr. Microarray analysis of differentiation-specific gene expression during 3T3-L1 adipogenesis. Gene 2004; 329:167-85; PMID:15033539; http://dx.doi.org/10.1016/j.gene.2003.12.012
  • Higuchi M, Dusting GJ, Peshavariya H, Jiang F, Hsiao ST, Chan EC, Liu GS. Differentiation of human adipose-derived stem cells into fat involves reactive oxygen species and Forkhead box O1 mediated upregulation of antioxidant enzymes. Stem Cells Dev 2013; 22:878-88; PMID:23025577; http://dx.doi.org/10.1089/scd.2012.0306
  • Qiang L, Farmer SR. C/EBPa-dependent induction of glutathione S-transferase ζ/maleylacetoacetate isomerase (GSTζ/MAAI) expression during the differentiation of mouse fibroblasts into adipocytes. Biochem Biophys Res Commun 2006; 340:845-51; PMID:16376852; http://dx.doi.org/10.1016/j.bbrc.2005.12.067
  • Jowsey IR, Smith SA, Hayes JD. Expression of the murine glutathione S-transferase α3 (GSTA3) subunit is markedly induced during adipocyte differentiation: activation of the GSTA3 gene promoter by the pro-adipogenic eicosanoid 15-deoxy-Δ12,14-prostaglandin J2. Biochem Biophys Res Commun 2003; 312:1226-35; PMID:14652005; http://dx.doi.org/10.1016/j.bbrc.2003.11.068
  • Si Y, Yoon J, Lee K. Flux profile and modularity analysis of time-dependent metabolic changes of de novo adipocyte formation. Am J Physiol Endocrinol Metab 2007; 292:E1637-46; PMID:17284573; http://dx.doi.org/10.1152/ajpendo.00670.2006
  • Oyadomari S, Takeda K, Takiguchi M, Gotoh T, Matsumoto M, Wada I, Akira S, Araki E, Mori M. Nitric oxide-induced apoptosis in pancreatic β cells is mediated by the endoplasmic reticulum stress pathway. Proc Natl Acad Sci U S A 2001; 98:10845-50; PMID:11526215; http://dx.doi.org/10.1073/pnas.191207498
  • Chambers KT, Unverferth JA, Weber SM, Wek RC, Urano F, Corbett JA. The role of nitric oxide and the unfolded protein response in cytokine induced β-cell death. Diabetes 2008; 57:124-32; PMID:17928398; http://dx.doi.org/10.2337/db07-0944
  • Koh EH, Park J-Y, Park H-S, Jeon MJ, Ryu JW, Kim M, Kim SY, Kim M-S, Kim S-W, Park IS, et al. Essential role of mitochondrial function in adiponectin synthesis in adipocytes. Diabetes 2007; 56:2973-81; PMID:17827403; http://dx.doi.org/10.2337/db07-0510
  • Alhusaini S, McGee K, Schisano B, Harte A, McTernan P, Kumar S, Tripathi G. Lipopolysaccharide, high glucose and saturated fatty acids induce endoplasmic reticulum stress in cultured primary human adipocytes: salicylate alleviates this stress. Biochem Biophys Res Commun 2010; 397:472-8; PMID:20515657; http://dx.doi.org/10.1016/j.bbrc.2010.05.138
  • Jeon MJ, Leem J, Ko MS, Jang JE, Park H-S, Kim HS, Kim M, Kim EH, Yoo HJ, Lee C-H, et al. Mitochondrial dysfunction and activation of iNOS are responsible for the palmitate-induced decrease in adiponectin synthesis in 3T3L1 adipocytes. Exp Mol Med 2012; 44:562-70; PMID:22809900; http://dx.doi.org/10.3858/emm.2012.44.9.064
  • Kawasaki N, Asada R, Saito A, Kanemoto S, Imaizumi K. Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue. Sci Rep 2012; 2:799; PMID:23150771; http://dx.doi.org/10.1038/srep00799
  • Jiao P, Ma J, Feng B, Zhang H, Alan Diehl J, Eugene Chin Y, Yan W, Xu H. FFA-induced adipocyte inflammation and insulin resistance: involvement of ER stress and IKKβ pathways. Obesity (Silver Spring) 2011; 19:483-91; PMID:20829802; http://dx.doi.org/10.1038/oby.2010.200
  • Chen Y, Chen M, Wu Z, Zhao S. Ox-LDL induces ER stress and promotes the adipokines secretion in 3T3-L1 adipocytes. PLoS One 2013; 8:e81379; PMID:24278099; http://dx.doi.org/10.1371/journal.pone.0081379
  • Dever TE, Chen JJ, Barber GN, Cigan AM, Feng L, Donahue TF, London IM, Katze MG, Hinnebusch AG. Mammalian eukaryotic initiation factor 2α kinases functionally substitute for GCN2 protein kinase in the GCN4 translational control mechanism of yeast. Proc Natl Acad Sci U S A 1993; 90:4616-20; PMID:8099443; http://dx.doi.org/10.1073/pnas.90.10.4616
  • Harding HP, Zhang Y, Ron D. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 1999; 397:271-4; PMID:9930704; http://dx.doi.org/10.1038/16729
  • Kyriakis JM, Banerjee P, Nikolakaki E, Dai T, Rubie EA, Ahmad MF, Avruch J, Woodgett JR. The stress-activated protein kinase subfamily of c-Jun kinases. Nature 1994; 369:156-60; PMID:8177321; http://dx.doi.org/10.1038/369156a0
  • Li LO, Klett EL, Coleman RA. Acyl-CoA synthesis, lipid metabolism and lipotoxicity. Biochim Biophys Acta 2010; 1801:246-51; PMID:19818872; http://dx.doi.org/10.1016/j.bbalip.2009.09.024
  • Hassan RH, Hainault I, Vilquin J-T, Samama C, Lasnier F, Ferré P, Foufelle F, Hajduch E. Endoplasmic reticulum stress does not mediate palmitate-induced insulin resistance in mouse and human muscle cells. Diabetologia 2012; 55:204-14; PMID:22006247; http://dx.doi.org/10.1007/s00125-011-2328-9
  • Weigert C, Brodbeck K, Staiger H, Kausch C, Machicao F, Haring HU, Schleicher ED. Palmitate, but not unsaturated fatty acids, induces the expression of interleukin-6 in human myotubes through proteasome-dependent activation of nuclear factor-κB. J Biol Chem 2004; 279:23942-52; PMID:15028733; http://dx.doi.org/10.1074/jbc.M312692200
  • Miller TA, LeBrasseur NK, Cote GM, Trucillo MP, Pimentel DR, Ido Y, Ruderman NB, Sawyer DB. Oleate prevents palmitate-induced cytotoxic stress in cardiac myocytes. Biochem Biophys Res Commun 2005; 336:309-15; PMID:16126172; http://dx.doi.org/10.1016/j.bbrc.2005.08.088
  • Diakogiannaki E, Welters HJ, Morgan NG. Differential regulation of the endoplasmic reticulum stress response in pancreatic β-cells exposed to long-chain saturated and monounsaturated fatty acids. J Endocrinol 2008; 197:553-63; PMID:18492819; http://dx.doi.org/10.1677/JOE-08-0041
  • Katsoulieris E, Mabley JG, Samai M, Green IC, Chatterjee PK. α-Linolenic acid protects renal cells against palmitic acid lipotoxicity via inhibition of endoplasmic reticulum stress. Eur J Pharmacol 2009; 623:107-12; PMID:19765573; http://dx.doi.org/10.1016/j.ejphar.2009.09.015
  • Akazawa Y, Cazanave S, Mott JL, Elmi N, Bronk SF, Kohno S, Charlton MR, Gores GJ. Palmitoleate attenuates palmitate-induced Bim and PUMA up-regulation and hepatocyte lipoapoptosis. J Hepatol 2010; 52:586-93; PMID:20206402; http://dx.doi.org/10.1016/j.jhep.2010.01.003
  • Salvadó L, Coll T, Gómez-Foix AM, Salmerón E, Barroso E, Palomer X, Vázquez-Carrera M. Oleate prevents saturated-fatty-acid-induced ER stress, inflammation and insulin resistance in skeletal muscle cells through an AMPK-dependent mechanism. Diabetologia 2013; 56:1372-82; PMID:23460021; http://dx.doi.org/10.1007/s00125-013-2867-3
  • Sommerweiß D, Gorski T, Richter S, Garten A, Kiess W. Oleate rescues INS-1E β-cells from palmitate induced apoptosis by preventing activation of the unfolded protein response. Biochem Biophys Res Commun 2013; 441:770-6; PMID:24189472; http://dx.doi.org/10.1016/j.bbrc.2013.10.130
  • Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 1997; 272:20963-6; PMID:9261091; http://dx.doi.org/10.1074/jbc.272.34.20963
  • Schroepfer GJ Jr. Oxysterols: modulators of cholesterol metabolism and other processes. Physiol Rev 2000; 80:361-554; PMID:10617772
  • Green H, Kehinde O. Sublines of mouse 3T3 cells that accumulate lipid. Cell 1974; 1:113-6; http://dx.doi.org/10.1016/0092-8674(74)90126-3
  • Green H, Kehinde O. Spontaneous heritable changes leading to increased adipose conversion in 3T3 cells. Cell 1976; 7:105-13; PMID:949738; http://dx.doi.org/10.1016/0092-8674(76)90260-9
  • Tsuchiya S, Yamabe M, Yamaguchi Y, Kobayashi Y, Konno T, Tada K. Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int J Cancer 1980; 26:171-6; PMID:6970727; http://dx.doi.org/10.1002/ijc.2910260208
  • Daigneault M, Preston JA, Marriott HM, Whyte MK, Dockrell DH. The identification of markers of macrophage differentiation in PMA-stimulated THP-1 cells and monocyte-derived macrophages. PLoS One 2010; 5:e8668; PMID:20084270; http://dx.doi.org/10.1371/journal.pone.0008668
  • Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65:55-63; PMID:6606682; http://dx.doi.org/10.1016/0022-1759(83)90303-4
  • Bradley RL, Fisher FF, Maratos-Flier E. Dietary fatty acids differentially regulate production of TNF-α and IL-10 by murine 3T3-L1 adipocytes. Obesity (Silver Spring) 2008; 16:938-44; PMID:18356844; http://dx.doi.org/10.1038/oby.2008.39
  • Chavez JA, Knotts TA, Wang LP, Li G, Dobrowsky RT, Florant GL, Summers SA. A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal transduction by saturated fatty acids. J Biol Chem 2003; 278:10297-303; PMID:12525490; http://dx.doi.org/10.1074/jbc.M212307200
  • Cox DJ, Strudwick N, Ali AA, Paton AW, Paton JC, Schröder M. Measuring signaling by the unfolded protein response. Methods Enzymol 2011; 491:261-92; PMID:21329805; http://dx.doi.org/10.1016/B978-0-12-385928-0.00015-8
  • Ku HH. Notes on use of propagation of error formulas. J Res Nat Bureau Standards Sect C — Eng Instrumentat 1966; 70:263-73; http://dx.doi.org/10.6028/jres.070C.025
  • Dunnett CW. New tables for multiple comparisons with control. Biometrics 1964; 20:482-91; http://dx.doi.org/10.2307/2528490
  • Dunnett CW. A multiple comparison procedure for comparing several treatments with a control. J Am Stat Assoc 1955; 50:1096-121; PMID:9252830; http://dx.doi.org/10.1080/01621459.1955.10501294

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.