The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Fatty acid—induced inflammation and insulin resistance in skeletal muscle and liver
Abstract
Plasma free fatty acid (FFA) levels are elevated in obesity. FFA, by causing insulin resistance in muscle, liver, and endothelial cells, contributes to the development of type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD). The mechanism through which FFA induces insulin resistance involves intramyocellular and intrahepatocellular accumulation of triglycerides and diacylglycerol, activation of several serine/threonine kinases, reduction in tyrosine phosphorylation of the insulin receptor substrate (IRS)-1/2, and impairment of the IRS/phosphatidylinositol 3-kinase pathway of insulin signaling. FFA also produces low-grade inflammation in skeletal muscle and liver through activation of nuclear factor-kappaB, resulting in release of several proinflammatory and proatherogenic cytokines. Thus, elevated FFA levels (due to obesity or to high-fat feeding) cause insulin resistance in skeletal muscle and liver, which contributes to the development of T2DM, and produce low-grade inflammation, which contributes to the development of atherosclerotic vascular diseases and NAFLD.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The actions of these stimuli serve to not only further induce tissue expression and secretion of IL-6 and TNFα (via the NFκB pathway, [3, 4]), but impair control of numerous signalling pathways regulating skeletal muscle insulin signalling, glucose uptake, mitochondrial fuel oxidation and respiration that impact negatively upon skeletal muscle energy homeostasis [2, 5–7].”
From Proinflammatory NFkB signalling promotes mitochondrial dysfunction in skeletal muscle in response to cellular fuel overloading (2019) · cites this paper as [5]
Citations
Cites
Role of Insulin Resistance in Human Disease
Reaven, G. M. (1988) · Diabetes · doi:10.2337/diab.37.12.1595 · Cited by 12,154
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760
Adipose Tissue as an Endocrine Organ
Kershaw, E. E., & Flier, J. S. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0395 · Cited by 5,522
Randle, P. J., Garland, P. B., Hales, C. N., & Newsholme, E. A. (1963) · The Lancet · doi:10.1016/s0140-6736(63)91500-9 · Cited by 5,093
Nuclear Factor-κB — A Pivotal Transcription Factor in Chronic Inflammatory Diseases
Barnes, P. J., & Karin, M. (1997) · New England Journal of Medicine · doi:10.1056/nejm199704103361506 · Cited by 4,622
Mechanisms of fatty acid-induced inhibition of glucose uptake.
Boden, G., Chen, X., Ruiz, J., White, J. V., & Rossetti, L. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117252 · Cited by 3,720
Self-citationKim, H. J., Park, S. Y., Choi, Y. J., Han, S. J., Lee, K. W., & Kim, D. J. (2013) · Hormone Research in Paediatrics · doi:10.1159/000348848 · Cited by 3,061
The Continuing Epidemics of Obesity and Diabetes in the United States
Mokdad, A. H. (2001) · JAMA · doi:10.1001/jama.286.10.1195 · Cited by 2,730
Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB
Cai, D., Yuan, M., Frantz, D. F., Melendez, P. A., Hansen, L., Lee, J., & Shoelson, S. E. (2005) · Nature Medicine · doi:10.1038/nm1166 · Cited by 2,245
Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM
Boden, G. (1997) · Diabetes · doi:10.2337/diab.46.1.3 · Cited by 1,728
Self-citationMedical Consequences of Obesity
Bray, G. A. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0535 · Cited by 1,614
Yu, C., Chen, Y., Cline, G. W., Zhang, D., Zong, H., Wang, Y., Bergeron, R., Kim, J. K., Cushman, S. W., Cooney, G. J., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200958200 · Cited by 1,561
Itani, S. I., Ruderman, N. B., Schmieder, F., & Boden, G. (2002) · Diabetes · doi:10.2337/diabetes.51.7.2005 · Cited by 1,390
Self-citationDresner, A., Laurent, D., Marcucci, M., Griffin, M. E., Dufour, S., Cline, G. W., Slezak, L. A., Andersen, D. K., Hundal, R. S., Rothman, D. L., et al. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5001 · Cited by 1,311
Boden, G., & Shulman, G. I. (2002) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.32.s3.3.x · Cited by 1,300
Self-citationStabel, S., & Parker, P. J. (1991) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(91)90042-k · Cited by 1,058
Effect of fatty acids on glucose production and utilization in man.
Ferrannini, E., Barrett, E. J., Bevilacqua, S., & DeFronzo, R. A. (1983) · Journal of Clinical Investigation · doi:10.1172/jci111133 · Cited by 1,050
Magnusson, I., Rothman, D. L., Katz, L. D., Shulman, R. G., & Shulman, G. I. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115997 · Cited by 757
Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance
Kim, J. K., Fillmore, J. J., Chen, Y., Yu, C., Moore, I. K., Pypaert, M., Lutz, E. P., Kako, Y., Velez-Carrasco, W., Goldberg, I. J., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.121164498 · Cited by 753
REGULATION OF PHOSPHOENOLPYRUVATE CARBOXYKINASE (GTP) GENE EXPRESSION
Hanson, R. W., & Reshef, L. (1997) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.66.1.581 · Cited by 729
Diabetes mellitus : a fundamental and clinical text
LeRoith, D., Taylor, S. I., & Olefsky, J. M. (2004) · Cited by 699
Boden, G., Lebed, B., Schatz, M., Homko, C., & Lemieux, S. (2001) · Diabetes · doi:10.2337/diabetes.50.7.1612 · Cited by 597
Self-citationInsulin Resistance and Risk of Congestive Heart Failure
Ingelsson, E., Sundström, J., Ärnlöv, J., Zethelius, B., & Lind, L. (2005) · JAMA · doi:10.1001/jama.294.3.334 · Cited by 569
Boden, G., She, P., Mozzoli, M., Cheung, P., Gumireddy, K., Reddy, P., Xiang, X., Luo, Z., & Ruderman, N. (2005) · Diabetes · doi:10.2337/diabetes.54.12.3458 · Cited by 528
Self-citationSantomauro, A. T., Boden, G., Silva, M. E., Rocha, D. M., Santos, R. F., Ursich, M. J., Strassmann, P. G., & Wajchenberg, B. L. (1999) · Diabetes · doi:10.2337/diabetes.48.9.1836 · Cited by 431
Self-citationSasaki, K., Cripe, T. P., Koch, S. R., Andreone, T. L., Petersen, D. D., Beale, E. G., & Granner, D. K. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42541-5 · Cited by 428
Nguyen, M. T. A., Satoh, H., Favelyukis, S., Babendure, J. L., Imamura, T., Sbodio, J. I., Zalevsky, J., Dahiyat, B. I., Chi, N.-W., & Olefsky, J. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504611200 · Cited by 411
Hotamisligil, G. S. (2005) · Diabetes · doi:10.2337/diabetes.54.suppl_2.s73 · Cited by 352
Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes.
Boden, G., & Chen, X. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118160 · Cited by 344
Self-citationRichardson, D. K., Kashyap, S., Bajaj, M., Cusi, K., Mandarino, S. J., Finlayson, J., DeFronzo, R. A., Jenkinson, C. P., & Mandarino, L. J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m408985200 · Cited by 259
FFA cause hepatic insulin resistance by inhibiting insulin suppression of glycogenolysis
Boden, G. H., Cheung, P., Stein, T. P., Kresge, K. M., & Mozzoli, M. A. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00429.2001 · Cited by 248
Self-citationTataranni, P. A., & Ortega, E. (2005) · Diabetes · doi:10.2337/diabetes.54.4.917 · Cited by 241
Free fatty acid-induced hepatic insulin resistance: a potential role for protein kinase C-δ
Lam, T. K. T., Yoshii, H., Haber, C. A., Bogdanovic, E., Lam, L., Fantus, I. G., & Giacca, A. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00038.2002 · Cited by 195
Gluconeogenesis in moderately and severely hyperglycemic patients with type 2 diabetes mellitus
Boden, G. H., Chen, X., & Stein, T. P. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.1.e23 · Cited by 167
Self-citationChung, S., Brown, J. M., Provo, J. N., Hopkins, R. G., & McIntosh, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508159200 · Cited by 160
Fanelli, C. G., Calderone, S., Epifano, L., Vincenzo, A. D., Modarelli, F., Pampanelli, S., Perriello, G., Feo, P. D., Brunetti, P., & Gerich, J. E. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116746 · Cited by 159
Gastaldelli, A., Toschi, E., Pettiti, M., Frascerra, S., Quiñones-Galvan, A., Sironi, A. M., Natali, A., & Ferrannini, E. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1807 · Cited by 150
Chen, H. C., Stone, S. J., Zhou, P., Buhman, K. K., & Farese, R. V. (2002) · Diabetes · doi:10.2337/diabetes.51.11.3189 · Cited by 134
Ravikumar, B., Carey, P. E., Snaar, J. E. M., Deelchand, D. K., Cook, D. B., Neely, R. D. G., English, P. T., Firbank, M., Morris, P. G., & Taylor, R. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00557.2004 · Cited by 124
Operation of Randle's Cycle in Patients With NIDDM
Bevilacqua, S., Buzzigoli, G., Bonadonna, R. C., Brandi, L. S., Oleggini, M., Boni, C. D., Geloni, M., & Ferrannini, E. (1990) · Diabetes · doi:10.2337/diab.39.3.383 · Cited by 104
Regulation of hepatic gluconeogenesis in the guinea pig by fatty acids and ammonia
Jomain-Baum, M., & Hanson, R. W. (1975) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)40681-9 · Cited by 36
Cited by
Sorted by citations
Role of Mitochondrial Dysfunction in Insulin Resistance
Kim, J.-A., Wei, Y., & Sowers, J. R. (2008) · Circulation Research · doi:10.1161/circresaha.107.165472 · Cited by 1,103
Cusi, K. J. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.02.003 · Cited by 940
The Perfect Storm: Obesity, Adipocyte Dysfunction, and Metabolic Consequences
de Ferranti, S. D., & Mozaffarian, D. (2008) · Clinical Chemistry · doi:10.1373/clinchem.2007.100156 · Cited by 755
Quehenberger, O., & Dennis, E. A. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1104901 · Cited by 470
Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis
Armstrong, M. J., Hull, D., Guo, K., Barton, D., Hazlehurst, J. M., Gathercole, L. L., Nasiri, M., Yu, J., Gough, S. C., Newsome, P. N., et al. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2015.08.038 · Cited by 456
Metadata
- Authors
- Boden, G.
- Affiliations
- Temple University Hospital (US)
- Corresponding author
- Boden, Guenther
- Venue
- Current Diabetes Reports
- Published
- 2006-05
- Volume
- 6
- Issue
- 3
- Pages
- 177-181
- ISSN
- 1534-4827 (ISSN-L)
- 1539-0829
- OpenAlex
- W2162614886
- Cited by
- 276
- References
- 42
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 15 · 2023: 9 · 2022: 12 · 2021: 15 · 2020: 14 · 2019: 11 · 2018: 14 · 2017: 9 · 2016: 8 · 2015: 25 · 2014: 14 · 2013: 18 · 2012: 20
- FWCI
- 11.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Current Diabetes Reports (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01 HL 733267)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058895)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Keywords
- free fatty acids, insulin resistance, low-grade inflammation, skeletal muscle, liver, type 2 diabetes, non-alcoholic fatty liver disease, obesity, high-fat feeding, diacylglycerol, triglyceride accumulation, insulin receptor substrate, phosphatidylinositol 3-kinase, NF-κB, inflammatory cytokines, atherosclerosis
- MeSH terms
- Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Humans, Inflammation, Insulin Resistance, Liver, Obesity, Muscle, Skeletal
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
