The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death
Open accessAbstract
Cell dysfunction and death induced by lipid accumulation in nonadipose tissues, or lipotoxicity, may contribute to the pathogenesis of obesity and type 2 diabetes. However, the mechanisms leading to lipotoxic cell death are poorly understood. We recently reported that, in Chinese hamster ovary (CHO) cells and in H9c2 cardiomyoblasts, lipid overload induced by incubation with 500 muM palmitate leads to intracellular accumulation of reactive oxygen species, which subsequently induce endoplasmic reticulum (ER) stress and cell death. Here, we show that palmitate also impairs ER function through a more direct mechanism. Palmitate was rapidly incorporated into saturated phospholipid and triglyceride species in microsomal membranes of CHO cells. The resulting membrane remodeling was associated with dramatic dilatation of the ER and redistribution of protein-folding chaperones to the cytosol within 5 h, indicating compromised ER membrane integrity. Increasing beta-oxidation, through the activation of AMP-activated protein kinase, decreased palmitate incorporation into microsomes, decreased the escape of chaperones to the cytosol, and decreased subsequent caspase activation and cell death. Thus, palmitate rapidly increases the saturated lipid content of the ER, leading to compromised ER morphology and integrity, suggesting that impairment of the structure and function of this organelle is involved in the cellular response to fatty acid overload.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Lipotoxic heart disease in obese rats: Implications for human obesity
Zhou, Y.-T., Grayburn, P., Karim, A., Shimabukuro, M., Higa, M., Baetens, D., Orci, L., & Unger, R. H. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.4.1784 · Cited by 1,265
Oxidative stress, ER stress, and the JNK pathway in type 2 diabetes
Kaneto, H., Matsuoka, T.-A., Nakatani, Y., Kawamori, D., Miyatsuka, T., Matsuhisa, M., & Yamasaki, Y. (2005) · Journal of Molecular Medicine · doi:10.1007/s00109-005-0640-x · Cited by 193
Aasum, E., Belke, D. D., Severson, D. L., Riemersma, R. A., Cooper, M., Andreassen, M., & Larsen, T. S. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00226.2001 · Cited by 154
Oleate prevents palmitate-induced cytotoxic stress in cardiac myocytes
Miller, T. A., LeBrasseur, N. K., Cote, G. M., Trucillo, M. P., Pimentel, D. R., Ido, Y., Ruderman, N. B., & Sawyer, D. B. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.08.088 · Cited by 146
Cited by
Oxidative stress and diabetic complications
Giacco, F., & Brownlee, M. (2010) · Circulation Research · doi:10.1161/circresaha.110.223545 · Cited by 5,461
Endoplasmic reticulum stress and the inflammatory basis of metabolic disease
Hotamisligil, G. S. (2010) · Cell · doi:10.1016/j.cell.2010.02.034 · Cited by 2,802
Molecular mechanisms of diabetic cardiomyopathy
Bugger, H., & Abel, E. D. (2014) · Diabetologia · doi:10.1007/s00125-014-3171-6 · Cited by 903
Gregor, M. F., & Hotamisligil, G. S. (2007) · Journal of Lipid Research · doi:10.1194/jlr.r700007-jlr200 · Cited by 586
The Role of Endoplasmic Reticulum Stress in the Progression of Atherosclerosis
Tabas, I. (2010) · Circulation Research · doi:10.1161/circresaha.110.224766 · Cited by 480
Seimon, T. A., Nadolski, M. J., Liao, X., Magallon, J., Nguyen, M., Feric, N. T., Koschinsky, M. L., Harkewicz, R., Witztum, J. L., Tsimikas, S., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.09.010 · Cited by 457
Mechanisms and consequences of macrophage apoptosis in atherosclerosis
Seimon, T., & Tabas, I. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r800032-jlr200 · Cited by 411
JNK1 and IKKβ: molecular links between obesity and metabolic dysfunction
Solinas, G., & Karin, M. (2010) · The FASEB Journal · doi:10.1096/fj.09-151340 · Cited by 347
Brookheart, R. T., Michel, C. I., & Schaffer, J. E. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.03.011 · Cited by 279
Self-citationProbing the Global Cellular Responses to Lipotoxicity Caused by Saturated Fatty Acids
Piccolis, M., Bond, L. M., Kampmann, M., Pulimeno, P., Chitraju, C., Jayson, C. B. K., Vaites, L. P., Boland, S., Lai, Z. W., Gabriel, K. R., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.01.036 · Cited by 269
Engin, A. B. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-48382-5_8 · Cited by 260
Lichtenstein, L., Mattijssen, F., de Wit, N. J., Georgiadi, A., Hooiveld, G. J., van der Meer, R., He, Y., Qi, L., Köster, A., Tamsma, J. T., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.11.002 · Cited by 251
Free fatty acids as modulators of the NLRP3 inflammasome in obesity/type 2 diabetes
Legrand-Poels, S., Esser, N., L’homme, L., Scheen, A., Paquot, N., & Piette, J. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.08.013 · Cited by 194
Adipose Tissue and Metabolic Health
An, S.-M., Cho, S.-H., & Yoon, J. C. (2023) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2023.0011 · Cited by 184
Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells
Du, J., Su, Y., Qian, C., Yuan, D., Miao, K., Lee, D., Ng, A. H. C., Wijker, R. S., Ribas, A., Levine, R. D., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18376-x · Cited by 171
Zhao, X., Peter, A., Fritsche, J., Elcnerova, M., Fritsche, A., Häring, H.-U., Schleicher, E. D., Xu, G., & Lehmann, R. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90748.2008 · Cited by 170
Egnatchik, R. A., Leamy, A. K., Noguchi, Y., Shiota, M., & Young, J. D. (2014) · Metabolism · doi:10.1016/j.metabol.2013.10.009 · Cited by 161
Regulatory role of small nucleolar RNAs in human diseases
Stepanov, G. A., Filippova, J. A., Komissarov, A. B., Kuligina, E. V., Richter, V. A., & Semenov, D. V. (2015) · BioMed Research International · doi:10.1155/2015/206849 · Cited by 154
Son, N.-H., Yu, S., Tuinei, J., Arai, K., Hamai, H., Homma, S., Shulman, G. I., Abel, E. D., & Goldberg, I. J. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40905 · Cited by 159
Inflammation meets metabolic disease: Gut feeling mediated by GLP-1
Zietek, T., & Rath, E. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00154 · Cited by 131
Lipolysis of triglyceride-rich lipoproteins, vascular inflammation, and atherosclerosis
Schwartz, E. A., & Reaven, P. D. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.09.021 · Cited by 130
Is fat so bad? Modulation of endoplasmic reticulum stress by lipid droplet formation
Hapala, I., Marza, E., & Ferreira, T. (2011) · Biology of the Cell · doi:10.1042/bc20100144 · Cited by 125
How Inflammation Impinges on NAFLD: A Role for Kupffer Cells
Duarte, N., Coelho, I. C., Patarrão, R. S., Almeida, J. I., Penha-Gonçalves, C., & Macedo, M. P. (2015) · BioMed Research International · doi:10.1155/2015/984578 · Cited by 120
“Excessive SFA entering hepatocytes are conducted to the formation of saturated phospholipids that are then integrated into ER membrane bilayers, affecting ER membrane fluidity [24].”
Different Serum Free Fatty Acid Profiles in NAFLD Subjects and Healthy Controls after Oral Fat Load
Gambino, R., Bugianesi, E., Rosso, C., Mezzabotta, L., Pinach, S., Alemanno, N., Saba, F., & Cassader, M. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17040479 · Cited by 101
The vascular contribution to Alzheimer's disease
Altman, R., & Rutledge, J. C. (2010) · Clinical Science · doi:10.1042/cs20100094 · Cited by 93
XBP1 links the 12-hour clock to NAFLD and regulation of membrane fluidity and lipid homeostasis
Meng, H., Gonzales, N. M., Lonard, D. M., Putluri, N., Zhu, B., Dacso, C. C., York, B., & O’Malley, B. W. (2020) · Nature Communications · doi:10.1038/s41467-020-20028-z · Cited by 67
Bojic, L. A., Sawyez, C. G., Telford, D. E., Edwards, J. Y., Hegele, R. A., & Huff, M. W. (2012) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.112.255208 · Cited by 51
Metadata
- Authors
- Borradaile, N. M., Han, X., Harp, J. D., Gale, S. E., Ory, D. S., & Schaffer, J. E.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 47
- Issue
- 12
- Pages
- 2726-2737
- ISSN
- 0022-2275 (ISSN-L)
- OpenAlex
- W2099125910
- Cited by
- 564
- References
- 4
- FWCI
- 7.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
