Inflammation triggered by saturated fat ingestion is linked to insulin resistance and hyperandrogenism in polycystic ovary syndrome
Open accessAbstract
CONTEXT: Inflammation and insulin resistance are often present in polycystic ovary syndrome (PCOS). OBJECTIVE: We determined the effect of saturated fat ingestion on mononuclear cell (MNC) nuclear factor-κB (NFκB) activation; NFκB, inhibitory-κBα (IκBα), and tumor necrosis factor-α (TNFα) gene expression; and circulating C-reactive protein (CRP) in women with PCOS. DESIGN: Cross-sectional study. SETTING: Academic medical center. PATIENTS: Twenty reproductive-age women with PCOS (10 lean, 10 with obesity) and 20 ovulatory controls (10 lean, 10 with obesity). MAIN OUTCOME MEASURES: Activated NFκB, NFκB heterodimer subunits, IκBα and TNFα messenger ribonucleic acid content and NFκB p65 and IκBα protein content were quantified in mononuclear cells (MNC), and CRP was measured in plasma from blood drawn fasting and 2, 3, and 5 h after saturated fat ingestion. Insulin sensitivity was derived from oral glucose tolerance testing (ISOGTT). Androgen secretion was assessed from blood drawn fasting and 24, 48, and 72 h after human chorionic gonadotropin (HCG) administration. RESULTS: In response to saturated fat ingestion, women with PCOS regardless of weight class exhibited lipid-induced increases in activated NFκB, NFκB, and TNFα gene expression and plasma CRP and decreases in IκBα protein compared with lean control subjects. Both PCOS groups exhibited lower ISOGTT and greater HCG-stimulated androgen secretion compared with control subjects. Lipid-stimulated NFκB activation was negatively correlated with ISOGTT, and positively correlated with HCG-stimulated androgen secretion. CONCLUSION: In PCOS, increases in NFκB activation and circulating CRP and decreases in IκBα protein following saturated fat ingestion are independent of obesity. Circulating MNC and excess adipose tissue are separate and distinct contributors to inflammation in this disorder.
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PCOS can be a consequence of a lipid-induced proinflammatory state.
“since PCOS can be the consequence of a lipid-induced proinflammatory state”
From PCOS and nutritional approaches: Differences between lean and obese phenotype (2021) · cites this paper as [15]
A better macronutrient distribution of the diet, despite not being intended for weight loss, may improve the constant inflammatory state.
“A better macronutrient distribution of the diet despite not being intended for weight loss may improve the constant inflammatory state.”
From PCOS and nutritional approaches: Differences between lean and obese phenotype (2021) · cites this paper as [15]
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Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
Detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III)
Grundy, S. M., Becker, D. M., Clark, L. T., Cooper, R., Denke, M. A., Howard, J. L., Hunninghake, D. B., Illingworth, D. R., Luepker, R. V., McBride, P. E., et al. (2002) · Civil War Book Review · Cited by 12,198 · see citing works
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 · see citing works
Matsuda, M., & DeFronzo, R. A. (1999) · Diabetes Care · doi:10.2337/diacare.22.9.1462 · Cited by 5,621 · see citing works
NF-κB: a key role in inflammatory diseases
Tak, P. P., & Firestein, G. S. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11830 · Cited by 3,918 · see citing works
Cinti, S., Mitchell, G., Barbatelli, G., Murano, I., Ceresi, E., Faloia, E., Wang, S., Fortier, M., Greenberg, A. S., & Obin, M. S. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m500294-jlr200 · Cited by 2,529 · see citing works
Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes
Evans, J. L., Goldfine, I. D., Maddux, B. A., & Grodsky, G. M. (2002) · Endocrine Reviews · doi:10.1210/er.2001-0039 · Cited by 2,232 · see citing works
Fauser, B. C. J. M., Tarlatzis, B. C., Rebar, R. W., Legro, R. S., Balen, A. H., Lobo, R., Carmina, E., Chang, J., Yildiz, B. O., Laven, J. S. E., et al. (2012) · Fertility and Sterility · doi:10.1016/j.fertnstert.2011.09.024 · Cited by 1,976 · see citing works
Diamanti-Kandarakis, E., & Dunaif, A. (2012) · Endocrine Reviews · doi:10.1210/er.2011-1034 · Cited by 1,947 · see citing works
The IκB-NF-κB Signaling Module: Temporal Control and Selective Gene Activation
Hoffmann, A., Levchenko, A., Scott, M. L., & Baltimore, D. (2002) · Science · doi:10.1126/science.1071914 · Cited by 1,866 · see citing works
March, W. A., Moore, V. M., Willson, K. J., Phillips, D. I. W., Norman, R. J., & Davies, M. J. (2010) · Human Reproduction · doi:10.1093/humrep/dep399 · Cited by 1,799 · see citing works
Dyslipidemia in obesity: Mechanisms and potential targets
Klop, B., Elte, J., & Cabezas, M. (2013) · Nutrients · doi:10.3390/nu5041218 · Cited by 1,665 · see citing works
Khovidhunkit, W., Kim, M.-S., Memon, R. A., Shigenaga, J. K., Moser, A. H., Feingold, K. R., & Grunfeld, C. (2004) · Journal of Lipid Research · doi:10.1194/jlr.r300019-jlr200 · Cited by 1,481 · see citing works
Tumor necrosis factor alpha inhibits signaling from the insulin receptor.
Hotamışlıgil, G. S., Murray, D. L., Choy, L., & Spiegelman, B. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.11.4854 · Cited by 1,206 · see citing works
Series Introduction: The transcription factor NF-κB and human disease
Baldwin, A. S. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11891 · Cited by 990 · see citing works
Lim, S. S., Davies, M. J., Norman, R. J., & Moran, L. J. (2012) · Human Reproduction Update · doi:10.1093/humupd/dms030 · Cited by 939 · see citing works
SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2
Rui, L., Yuan, M., Frantz, D., Shoelson, S., & White, M. F. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200444200 · Cited by 904 · see citing works
Ablation of CD11c-Positive Cells Normalizes Insulin Sensitivity in Obese Insulin Resistant Animals
Patsouris, D., Li, P.-P., Thapar, D., Chapman, J., Olefsky, J. M., & Neels, J. G. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.08.015 · Cited by 804 · see citing works
Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome
Legro, R. S., Kunselman, A. R., & Dunaif, A. (2001) · The American Journal of Medicine · doi:10.1016/s0002-9343(01)00948-2 · Cited by 622 · see citing works
The effect of obesity on polycystic ovary syndrome: a systematic review and meta‐analysis
Lim, S. S., Norman, R. J., Davies, M. J., & Moran, L. J. (2013) · Obesity Reviews · doi:10.1111/j.1467-789x.2012.01053.x · Cited by 539 · see citing works
Role of Oxidants in NF-κB Activation and TNF-α Gene Transcription Induced by Hypoxia and Endotoxin
Chandel, N. S., Trzyna, W., McClintock, D. S., & Schumacker, P. T. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.2.1013 · Cited by 536 · see citing works
Zhang, L. H., Rodriguez, H., Ohno, S., & Miller, W. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.23.10619 · Cited by 455 · see citing works
Emanuelli, B., Peraldi, P., Filloux, C., Carine Chavey, A., Freidinger, K., Hilton, D. J., Hotamışlıgil, G. S., & OBBERGHEN, E. V. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104602200 · Cited by 449 · see citing works
Carmina, E., Bucchieri, S., Esposito, A., Del Puente, A., Mansueto, P., Orio, F., Di Fede, G., & Rini, G. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2725 · Cited by 317 · see citing works
Generation of p50 subunit of NF-kB by processing of p105 through an ATP-dependent pathway
Fan, C., & Maniatis, T. (1991) · Nature · doi:10.1038/354395a0 · Cited by 308 · see citing works
Deopurkar, R., Ghanim, H., Friedman, J., Abuaysheh, S., Sia, C. L., Mohanty, P., Viswanathan, P., Chaudhuri, A., & Dandona, P. (2010) · Diabetes Care · doi:10.2337/dc09-1630 · Cited by 246 · see citing works
Mohanty, P., Ghanim, H., Hamouda, W., Aljada, A., Garg, R., & Dandona, P. (2002) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/75.4.767 · Cited by 239 · see citing works
Varma, V., Yao-Borengasser, A., Rasouli, N., Nolen, G. T., Phanavanh, B., Starks, T., Gurley, C., Simpson, P., McGehee, R. E., Kern, P. A., et al. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90885.2008 · Cited by 229 · see citing works
González, F., Rote, N. S., Minium, J., & Kirwan, J. P. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2327 · Cited by 228 · see citing works
Self-citationLegro, R. S., Schlaff, W. D., Diamond, M. P., Coutifaris, C., Casson, P. R., Brzyski, R. G., Christman, G. M., Trussell, J. C., Krawetz, S. A., Snyder, P. J., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1123 · Cited by 213 · see citing works
TNFα release by the nonfat cells of human adipose tissue
Fain, J. N., Bahouth, S. W., & Madan, A. K. (2004) · International Journal of Obesity · doi:10.1038/sj.ijo.0802594 · Cited by 202 · see citing works
Feingold, K. R., Harðardóttir, I., Memon, R. A., Krul, E. J. T., Moser, A. H., Taylor, J. M., & Grünfeld, C. (1993) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)35355-4 · Cited by 181 · see citing works
Banaszewska, B., Wrotyńska-Barczyńska, J., Spaczynski, R. Z., Pawelczyk, L., & Duleba, A. J. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-1858 · Cited by 173 · see citing works
Brewer, H. B. (1999) · The American Journal of Cardiology · doi:10.1016/s0002-9149(99)00308-2 · Cited by 157 · see citing works
Dandona, P., Mohanty, P., Hamouda, W., Ghanim, H., Aljada, A., Garg, R., & Kumar, V. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.6.7745 · Cited by 135 · see citing works
Tumor Necrosis Factor-α Stimulates Proliferation of Rat Ovarian Theca-Interstitial Cells1
Spaczyński, R., Arici, A. M., & Dulęba, A. J. (1999) · Biology of Reproduction · doi:10.1095/biolreprod61.4.993 · Cited by 133 · see citing works
Promoter of the human NF-kappa B p50/p105 gene. Regulation by NF-kappa B subunits and by c-REL
Cogswell, P. C., Scheinman, R. I., & Baldwin, A. S. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.150.7.2794 · Cited by 102 · see citing works
González, F., Minium, J., Rote, N. S., & Kirwan, J. P. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0694 · Cited by 97 · see citing works
Self-citationCiaraldi, T. P., Kolterman, O., & Olefsky, J. M. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110342 · Cited by 93 · see citing works
González, F., Considine, R. V., Abdelhadi, O. A., & Acton, A. J. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01143 · Cited by 91 · see citing works
Self-citationControl of NF–κB transcriptional activation by signal induced proteolysis of IκBα
Hay, R. T., Vuillard, L. M., Desterro, J. M. P., & Rodríguez, M. S. (1999) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.1999.0504 · Cited by 89 · see citing works
Modan, M., Harris, M. I., & Halkin, H. (1989) · Diabetes · doi:10.2337/diab.38.12.1630 · Cited by 80 · see citing works
Fox, C. W., Zhang, L., Sohni, A., Doblado, M., Wilkinson, M., Chang, R. J., & Dulęba, A. J. (2019) · Endocrinology · doi:10.1210/en.2019-00588 · Cited by 78 · see citing works
A central role for hepatocyte growth factor in adipose tissue angiogenesis
Bell, L. N., Cai, L., Johnstone, B. H., Traktuev, D. O., March, K. L., & Considine, R. V. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00272.2007 · Cited by 77 · see citing works
Self-citationDeopurkar, R., Ghanim, G., Friedman, & Abuaysheh (2010) · Diabetes Care · Cited by 71 · see citing works
González, F., Nair, K. S., Daniels, J. K., Basal, E., & Schimke, J. M. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00416.2011 · Cited by 70 · see citing works
Self-citationGonzález, F., Considine, R. V., Abdelhadi, O. A., & Acton, A. J. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00987 · Cited by 60 · see citing works
Self-citationGonzález, F., Sia, C. L., Shepard, M. K., Rote, N. S., & Minium, J. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2131 · Cited by 46 · see citing works
Self-citationGonzález, F., Sia, C. L., Shepard, M. K., Rote, N. S., & Minium, J. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-2046 · Cited by 35 · see citing works
Self-citationObese Reproductive‐Age Women Exhibit a Proatherogenic Inflammatory Response During Hyperglycemia
González, F., Rote, N. S., Minium, J., O’Leary, V. B., & Kirwan, J. P. (2007) · Obesity · doi:10.1038/oby.2007.289 · Cited by 33 · see citing works
Self-citationOrtego, M., Gómez-Hernández, A., Vidal, C., et al. (2005) · Journal of Cardiovascular Pharmacology · doi:10.1097/01.fjc.0000159042.50488.e5 · Cited by 31 · see citing works
Glucose ingestion stimulates atherothrombotic inflammation in polycystic ovary syndrome
González, F., Kirwan, J. P., Rote, N. S., & Minium, J. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00491.2012 · Cited by 30 · see citing works
Self-citationTranslocation of p47phox and Activation of NADPH Oxidase in Mononuclear Cells
Aljada, A., Ghanim, H., & Dandona, P. (2003) · Humana Press eBooks · doi:10.1385/1-59259-274-0:99 · Cited by 20 · see citing works
High fat diet and aging are associated with macrophage infiltration in mice ovaries
Thornton, K. L., Asemota, O. A., Jindal, S., et al. (2015) · Fertility and Sterility · doi:10.1016/j.fertnstert.2015.07.322 · Cited by 8 · see citing works
González, F., Mather, K. J., Considine, R. V., et al. (2015) · Fertility and Sterility · doi:10.1016/j.fertnstert.2015.07.064 · Cited by 5 · see citing works
Self-citationGonzález, F., Considine, R. V., Abdelhadi, O. A., et al. (2016) · Fertility and Sterility · doi:10.1016/j.fertnstert.2016.07.104 · Cited by 2 · see citing works
Self-citation
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Research works printed but not linked: 7
- Hotamisligil GS, Murray DL, Choy LN, Spiegelman BM. Tumor necrosis factor α inhibits signaling from the insulin receptor. Proc Natl Acad Sci U S A. 1994;91(11):4854-4858.
- Baldwin AS Jr. The transcription factor NFκB and human disease. J Clin Invest. 2001;107(1):3-6.
- Tak PP, Firestein GS. NF-kappaB: a key role in inflammatory dis- eases. J Clin Invest. 2001;107(1):7-11.
- González F, Kirwan JP, Rote NS, Minium J. Glucose inges- tion stimulates atherothrombotic inflammation in poly- cystic ovary syndrome. Am J Physiol Endocrinol Metab. 2013;304(4):E375-E383.
- Yeh ST. Using a trapezoidal rule for the area under a curve cal- culation -SAS advanced tutorial. In: Proceedings of the 27th Annual Conference of SAS Users Group International. Orlando, FL; 2002: Abstract 229.
- González F, Rote NS, Minium J, Kirwan JP. Insulin sensitivity and hyperandrogenism in polycystic ovary syndrome are related to activated nuclear factor κB from mononuclear cells in the fasting Downloaded from https://academic.oup.com/jcem/article/105/6/e2152/5788228 by guest on 16 August 2023 doi:10.1210/clinem/dgaa108 https://academic.oup.com/jcem e2167 state. In: Program of the 89th Meeting of the Endocrine Society. Toronto, ON; June 12-16, 2007.
- Khovidhunkit W, Kim MS, Memon RA, et al. Effects of in- fection and inflammation on lipid and lipoprotein metab- olism: mechanisms and consequences to the host. J Lipid Res. 2004;45(7):1169-1196.
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- Authors
- González, F., Considine, R. V., Abdelhadi, O. A., & Acton, A. J.
- Affiliations
- University of Illinois Chicago (US)
- Indiana University School of Medicine (US)
- Corresponding author
- González, Frank
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2020-03-06
- Volume
- 105
- Issue
- 6
- Pages
- e2152-e2167
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC7150616
- OpenAlex
- W3009505948
- Cited by
- 60
- References
- 57
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 8 · 2023: 2 · 2022: 16 · 2021: 9 · 2020: 8 · 2019: 1
- FWCI
- 7.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- National Institutes of Health (R01 DK107605, UL1TR002529, P30 DK097512)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Keywords
- polycystic ovary syndrome, inflammation, insulin resistance, hyperandrogenism, NF-κB activation, IκBα, TNF-α, C-reactive protein, mononuclear cells, androgen secretion, obesity, dietary fat
- MeSH terms
- Adolescent, Adult, Cross-Sectional Studies, Fatty Acids, Female, Follow-Up Studies, Humans, Inflammation, Insulin Resistance, Obesity, Polycystic Ovary Syndrome, Prognosis, Thinness, Case-Control Studies, Hyperandrogenism, Young Adult
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