The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase
Open accessAbstract
A previous study reported the increased expression of the cytokine TNF in the adipose tissue of genetically obese rodents. To examine this paradigm in humans, we studied TNF expression in lean, obese, and reduced-obese human subjects. TNF mRNA was demonstrated in human adipocytes and adipose tissue by Northern blotting and PCR. TNF protein was quantitated by Western blotting and ELISA in both adipose tissue and the medium surrounding adipose tissue. Using quantitative reverse transcriptase PCR (RT-PCR), TNF mRNA levels were examined in the adipose tissue of 39 nondiabetic subjects, spanning a broad range of body mass index (BMI). There was a significant increase in adipose TNF mRNA levels with increasing adiposity. There was a significant correlation between TNF mRNA and percent body fat (r = 0.46, P < 0.05, n = 23). TNF mRNA tended to decrease in very obese subjects, but when subjects with a BMI > 45 kg/m2 were excluded, there was a significant correlation between TNF mRNA and BMI (r = 0.37, P < 0.05, n = 32). In addition, there was a significant decrease in adipose TNF with weight loss. In 11 obese subjects who lost between 14 and 66 kg (mean 34.7 kg, or 26.6% of initial weight), TNF mRNA levels decreased to 58% of initial levels after weight loss (P < 0.005), and TNF protein decreased to 46% of initial levels (P < 0.02). TNF is known to inhibit LPL activity. When fasting adipose LPL activity was measured in these subjects, there was a significant inverse relationship between TNF expression and LPL activity (r = -0.39, P < 0.02, n = 39). With weight loss, LPL activity increased to 411% of initial levels. However, the magnitude of the increase in LPL did not correlate with the decrease in TNF. Thus, TNF is expressed in human adipocytes. TNF is elevated in most obese subjects and is decreased by weight loss. In addition, there is an inverse relationship between TNF and LPL expression. These data suggest that endogenous TNF expression in adipose tissue may help limit obesity in some subjects, perhaps by increasing insulin resistance and decreasing LPL.
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
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.
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?
Increased plasma concentrations of TNFα in obese humans fall following caloric restriction and weight loss.
“Increased plasma concentrations of TNFα were also demonstrated in obese humans and these were shown to fall following caloric restriction and weight loss [2, 3].”
From Bariatric surgery: remission of inflammation, cardiometabolic benefits, and common adverse effects (2020) · cites this paper as [3]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
Chomczynski, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1006/abio.1987.9999 · Cited by 65,240 · see citing works
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
Chomczyński, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90021-2 · Cited by 47,092 · see citing works
A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity
Feinberg, A. P., & Vogelstein, B. (1983) · Analytical Biochemistry · doi:10.1016/0003-2697(83)90418-9 · Cited by 24,512 · see citing works
Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance
Hotamisligil, G. S., Shargill, N. S., & Spiegelman, B. M. (1993) · Science · doi:10.1126/science.7678183 · Cited by 7,518 · see citing works
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 · see citing works
A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity
(1984) · Analytical Biochemistry · doi:10.1016/0003-2697(84)90381-6 · Cited by 4,950 · see citing works
Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis.
Keffer, J., Probert, L., Cazlaris, H., Georgopoulos, S., Kaslaris, E., Kioussis, D., & Kollias, G. (1991) · EMBO Journal · doi:10.1002/j.1460-2075.1991.tb04978.x · Cited by 1,675 · see citing works
Quantitation of mRNA by the polymerase chain reaction.
Wang, A. M., DOYLE, M. V., & Mark, D. F. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.24.9717 · Cited by 1,638 · see citing works
Cachectin and tumour necrosis factor as two sides of the same biological coin
Beutler, B., & Cerami, A. (1986) · Nature · doi:10.1038/320584a0 · Cited by 1,633 · see citing works
The Response to Long-Term Overfeeding in Identical Twins
Bouchard, C., Tremblay, A., Després, J.-P., Nadeau, A., Lupien, P. J., Thériault, G., Dussault, J., Moorjani, S., Pinault, S., & Fournier, G. (1990) · New England Journal of Medicine · doi:10.1056/nejm199005243222101 · Cited by 1,278 · see citing works
Identity of tumour necrosis factor and the macrophage-secreted factor cachectin
Beutler, B., Greenwald, D., Hulmes, J. D., Chang, M., Pan, Y.-C. E., Mathison, J. C., Ulevitch, R. J., & Cerami, A. (1985) · Nature · doi:10.1038/316552a0 · Cited by 1,132 · see citing works
Flier, J. S., Underhill, L. H., & Eckel, R. H. (1989) · New England Journal of Medicine · doi:10.1056/nejm198904203201607 · Cited by 973 · see citing works
Hotamisligil, G. S., Budavari, A., Murray, D., & Spiegelman, B. M. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117495 · Cited by 819 · see citing works
Tumors secreting human TNF/cachectin induce cachexia in mice
Oliff, A. I., Defeo-Jones, D., BOYER, M. E., Martinez, D., KIEFER, D. M., Vuocolo, G. A., Wolfe, A. L., & Socher, S. H. (1987) · Cell · doi:10.1016/0092-8674(87)90028-6 · Cited by 640 · see citing works
Siebert, P. D., & Larrick, J. W. (1992) · Nature · doi:10.1038/359557a0 · Cited by 537 · see citing works
Human Lipoprotein Lipase Complementary DNA Sequence
Wion, K. L., Kirchgessner, T. G., Lusis, A. J., Schotz, M. C., & Lawn, R. M. (1987) · Science · doi:10.1126/science.3823907 · Cited by 479 · see citing works
Estimation of human body composition by electrical impedance methods: a comparative study
Segal, K. R., Gutin, B., Presta, E., Wang, J., & Itallie, T. B. V. (1985) · Journal of Applied Physiology · doi:10.1152/jappl.1985.58.5.1565 · Cited by 463 · see citing works
Metabolic Disturbances and Wasting in the Acquired Immunodeficiency Syndrome
Flier, J. S., Underhill, L. H., Grunfeld, C., & Feingold, K. R. (1992) · New England Journal of Medicine · doi:10.1056/nejm199207303270506 · Cited by 398 · see citing works
Hofmann, C. A., Lorenz, K., Braithwaite, S. S., Colca, J. R., Palazuk, B. J., Hotamışlıgil, G. S., & Spiegelman, B. M. (1994) · Endocrinology · doi:10.1210/endo.134.1.8275942 · Cited by 387 · see citing works
A simple method to determine fat cell size and number in four mammalian species
GIROLAMO, M. D., Mendlinger, S., & Fertig, J. (1971) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1971.221.3.850 · Cited by 371 · see citing works
Stephens, J. M., & Pekala, P. H. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)54714-1 · Cited by 370 · see citing works
Garvey, W. T., Maianu, L., Huecksteadt, T. P., Birnbaum, M. J., Molina, J. M., & Ciaraldi, T. P. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115068 · Cited by 324 · see citing works
Diet composition, energy intake, and exercise in relation to body fat in men and women
Miller, W. C., Lindeman, A. K., Wallace, J. P., & Niederpruem, M. (1990) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/52.3.426 · Cited by 303 · see citing works
Insulin stimulation of adipose tissue lipoprotein lipase. Use of the euglycemic clamp technique.
Sadur, C. N., & Eckel, R. H. (1982) · Journal of Clinical Investigation · doi:10.1172/jci110547 · Cited by 288 · see citing works
Pykälistö, O., Smith, P. H., & Brunzell, J. D. (1975) · Journal of Clinical Investigation · doi:10.1172/jci108185 · Cited by 284 · see citing works
Interferons and tumor necrosis factors have similar catabolic effects on 3T3 L1 cells.
Patton, J. S., Shepard, H. M., Wilking, H., Lewis, G., Aggarwal, B. B., Eessalu, T. E., Gavin, L. A., & Grünfeld, C. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.21.8313 · Cited by 277 · see citing works
Regulation of adipocyte gene expression in differentiation and syndromes of obesity/diabetes.
Spiegelman, B. M., Choy, L., Hotamışlıgil, G. S., Graves, R. A., & Tontonoz, P. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53107-0 · Cited by 275 · see citing works
Lipoprotein lipase suppression in 3T3-L1 cells by an endotoxin-induced mediator from exudate cells.
Kawakami, M., Pekala, P. H., Lane, M. D., & Cerami, A. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.3.912 · Cited by 267 · see citing works
Through thick and thin: Wasting, obesity, and TNFα
Spiegelman, B. M., & Hotamışlıgil, G. S. (1993) · Cell · doi:10.1016/0092-8674(93)90243-j · Cited by 217 · see citing works
Current understanding of the etiology of obesity: genetic and nongenetic factors
Bouchard, C. (1991) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/53.6.1561s · Cited by 208 · see citing works
Glycerol production in subcutaneous adipose tissue in lean and obese humans.
Jansson, P., Larsson, A., Smith, U., & Lönnroth, P. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115756 · Cited by 196 · see citing works
Freidenberg, G. R., Reichart, D. R., Olefsky, J. M., & Henry, R. R. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113744 · Cited by 194 · see citing works
Ong, J. M., Kirchgessner, T. G., Schotz, M. C., & Kern, P. A. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)37651-8 · Cited by 191 · see citing works
Self-citationQuantitation of mRNA by the polymerase chain reaction
(1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.7.2865-a · Cited by 185 · see citing works
Insulin resistance: an adaptation for weight maintenance
Eckel, R. H. (1992) · The Lancet · doi:10.1016/0140-6736(92)92633-q · Cited by 168 · see citing works
Fried, S. K., & Zechner, R. (1989) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38211-0 · Cited by 163 · see citing works
Ong, J. M., & Kern, P. A. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114155 · Cited by 158 · see citing works
Self-citationIncrease of adipose tissue lipoprotein lipase activity with weight loss.
Schwartz, R. S., & Brunzell, J. D. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110171 · Cited by 153 · see citing works
Taskinen, M., & Nikkil�, E. A. (1979) · Diabetologia · doi:10.1007/bf01236268 · Cited by 145 · see citing works
Experimental obesity, dietary-induced thermogenesis, and their clinical implications
Sims, E. A. H. (1976) · Clinics in Endocrinology and Metabolism · doi:10.1016/s0300-595x(76)80027-8 · Cited by 135 · see citing works
Kern, P. A., Ong, J. M., Saffari, B., & Carty, J. (1990) · New England Journal of Medicine · doi:10.1056/nejm199004123221506 · Cited by 130 · see citing works
Self-citationControl of lipolysis and its relevance to development of obesity in man
Amer, P. (1988) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610040507 · Cited by 123 · see citing works
Total and resting energy expenditure in obese women reduced to ideal body weight.
Amatruda, J. M., Statt, M. C., & Welle, S. L. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116695 · Cited by 117 · see citing works
Grünfeld, C., Gulli, R., Moser, A. H., Gavin, L. A., & Feingold, K. R. (1989) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38349-8 · Cited by 116 · see citing works
The regulation of adipose tissue and muscle lipoprotein lipase in runners by detraining.
Simsolo, R. B., Ong, J. M., & Kern, P. A. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116813 · Cited by 109 · see citing works
Self-citationChronic TNF Infusion Causes Anorexia But Not Accelerated Nitrogen Loss
MICHIE, H. R., Sherman, M. L., Spriggs, D. R., CHRISTIE, M., Wilmore, D. W., & Rounds, J. D. (1989) · Annals of Surgery · doi:10.1097/00000658-198901000-00002 · Cited by 87 · see citing works
Effect of improved diabetes control on the expression of lipoprotein lipase in human adipose tissue.
Simsolo, R. B., Ong, J., Saffari, B., & Kern, P. A. (1992) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)41886-3 · Cited by 81 · see citing works
Self-citationDomain exchange: characterization of a chimeric lipase of hepatic lipase and lipoprotein lipase.
Wong, H., Davis, R. C., Nikazy, J., Seebart, K. E., & Schotz, M. C. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.24.11290 · Cited by 75 · see citing works
Kern, P. A., SVOBODA, M. E., Eckel, R. H., & Wyk, J. J. V. (1989) · Diabetes · doi:10.2337/diab.38.6.710 · Cited by 75 · see citing works
Self-citationKobayashi, J., Nishida, T., Ameis, D., Stahnke, G., Schotz, M. C., Hashimoto, H., Fukamachi, I., Shirai, K., Saitō, Y., & Yoshida, S. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(05)80113-5 · Cited by 68 · see citing works
Grünfeld, C., Wilking, H., Neese, R. A., Gavin, L. A., Moser, A. H., Gulli, R., Serio, M., & Feingold, K. R. (1989) · PubMed · Cited by 68 · see citing works
Insulin Regulation of Lipoprotein Lipase in Cultured Isolated Rat Adipocytes*
Eckel, R. H., Prasad, J. E., Kern, P. A., et al. (1984) · Endocrinology · doi:10.1210/endo-114-5-1665 · Cited by 60 · see citing works
Self-citationRegulation of lipoprotein lipase in primary cultures of isolated human adipocytes.
Kern, P. A., Marshall, S., & Eckel, R. H. (1985) · Journal of Clinical Investigation · doi:10.1172/jci111675 · Cited by 51 · see citing works
Self-citationMeasurement of mRNA by quantitative PCR with a nonradioactive label.
Powell, E. E., & Kroon, P. A. (1992) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)41626-8 · Cited by 48 · see citing works
Kern, P. A. (1988) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38483-2 · Cited by 48 · see citing works
Self-citationRegulation of lipoprotein lipase immunoreactive mass in isolated human adipocytes.
Kern, P. A., Ong, J. M., Goers, J. W. F., et al. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113332 · Cited by 41 · see citing works
Self-citationThe origin and glyceride distribution of fatty acids in rat adipose tissue.
Hollenberg, C. H. (1966) · Journal of Clinical Investigation · doi:10.1172/jci105333 · Cited by 41 · see citing works
Pekala, P. H., Price, S. R., Horn, C. A., et al. (1984) · PubMed · Cited by 30 · see citing works
Andus, T., Targan, S. R., Deem, R. L., et al. (1993) · PubMed · Cited by 29 · see citing works
Self-citationKern, P., Svoboda, M. E., Eckel, R. H., et al. (1989) · Diabetes · doi:10.2337/diabetes.38.6.710 · Cited by 29 · see citing works
Self-citationMackay, A. G., Oliver, J. D., & Rogers, M. P. (1990) · Biochemical Journal · doi:10.1042/bj2690123 · Cited by 28 · see citing works
Coiro, V., Volpi, R., Capretti, L., et al. (1994) · Metabolism · doi:10.1016/0026-0495(94)90086-8 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Inflammation and metabolic disorders
Hotamisligil, G. S. (2006) · Nature · doi:10.1038/nature05485 · Cited by 9,199 · see citing works
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 · see citing works
Adipokines in inflammation and metabolic disease
Ouchi, N., Parker, J. L., Lugus, J. J., & Walsh, K. (2011) · Nature Reviews Immunology · doi:10.1038/nri2921 · Cited by 4,625 · see citing works
Inflammation, stress, and diabetes
Wellen, K. E., & Hotamisligil, G. S. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25102 · Cited by 4,143 · see citing works
Maffei, M., Halaas, J., Ravussin, E., Pratley, R. E., Lee, G. H., Zhang, Y., Fei, H., Kim, S., Lallone, R., Ranganathan, S., et al. (1995) · Nature Medicine · doi:10.1038/nm1195-1155 · Cited by 3,725 · see citing works
Self-citationPoirier, P., Giles, T. D., Bray, G. A., Hong, Y., Stern, J. S., Pi-Sunyer, F. X., & Eckel, R. H. (2006) · Circulation · doi:10.1161/circulationaha.106.171016 · Cited by 3,165 · see citing works
Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome
Wajchenberg, B. L. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.6.0415 · Cited by 2,961 · see citing works
Hotamisligil, G. S., Peraldi, P., Budavari, A., Ellis, R., White, M. F., & Spiegelman, B. M. (1996) · Science · doi:10.1126/science.271.5249.665 · Cited by 2,630 · see citing works
Nonalcoholic Fatty Liver Disease
Marchesini, G., Brizi, M., Bianchi, G., Tomassetti, S., Bugianesi, E., Lenzi, M., McCullough, A. J., Natale, S., Forlani, G., & Melchionda, N. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1844 · Cited by 2,581 · see citing works
Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis
Tilg, H., & Moschen, A. R. (2010) · Hepatology · doi:10.1002/hep.24001 · Cited by 2,548 · see citing works
Yudkin, J. S., Stehouwer, C. D. A., Emeis, J. J., & Coppack, S. W. (1999) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.19.4.972 · Cited by 2,465 · see citing works
Mechanisms for Insulin Resistance: Common Threads and Missing Links
Samuel, V. T., & Shulman, G. I. (2012) · Cell · doi:10.1016/j.cell.2012.02.017 · Cited by 2,294 · see citing works
Protection from obesity-induced insulin resistance in mice lacking TNF-α function
Uysal, K. T., Wiesbrock, S. M., Marino, M. W., & Hotamisligil, G. S. (1997) · Nature · doi:10.1038/39335 · Cited by 2,234 · see citing works
Inflammation: the link between insulin resistance, obesity and diabetes
Dandona, P. (2004) · Trends in Immunology · doi:10.1016/j.it.2003.10.013 · Cited by 2,170 · see citing works
Kern, P. A., Ranganathan, S., Li, C., Wood, L., & Ranganathan, G. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.5.e745 · Cited by 1,883 · see citing works
Self-citationRelationship between Adipocyte Size and Adipokine Expression and Secretion
Skurk, T., Alberti-Huber, C., Herder, C., & Hauner, H. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1055 · Cited by 1,288 · see citing works
The intestinal microbiota fuelling metabolic inflammation
Tilg, H., Zmora, N., Adolph, T. E., & Elinav, E. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0198-4 · Cited by 1,089 · see citing works
Makki, K., Froguel, P., & Wolowczuk, I. (2013) · ISRN Inflammation · doi:10.1155/2013/139239 · Cited by 1,085 · see citing works
Mikkelsen, K., Stojanovska, L., Polenakovic, M., Bosevski, M., & Apostolopoulos, V. (2017) · Maturitas · doi:10.1016/j.maturitas.2017.09.003 · Cited by 1,072 · see citing works
Pro-inflammatory cytokines: The link between obesity and osteoarthritis
Wang, T., & He, C. (2018) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2018.10.002 · Cited by 1,034 · see citing works
Rotter, V., Nagaev, I., & Smith, U. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301977200 · Cited by 1,062 · see citing works
Suganami, T., Nishida, J., & Ogawa, Y. (2005) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000183883.72263.13 · Cited by 1,056 · see citing works
Ziccardi, P., Nappo, F., Giugliano, G., Esposito, K., Marfella, R., Cioffi, M., D’Andrea, F., Molinari, A. M., & Giugliano, D. (2002) · Circulation · doi:10.1161/hc0702.104279 · Cited by 994 · see citing works
Klein, S., Burke, L. E., Bray, G. A., Blair, S., Allison, D. B., Pi-Sunyer, X., Hong, Y., & Eckel, R. H. (2004) · Circulation · doi:10.1161/01.cir.0000145546.97738.1e · Cited by 934 · see citing works
Insulin Resistance and Chronic Cardiovascular Inflammatory Syndrome
Fernández-Real, J. M., & Ricart, W. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0010 · Cited by 886 · see citing works
Adiponectin Expression From Human Adipose Tissue
Kern, P. A., Di Gregorio, G. B., Lu, T., Rassouli, N., & Ranganathan, G. (2003) · Diabetes · doi:10.2337/diabetes.52.7.1779 · Cited by 875 · see citing works
Self-citationNonalcoholic Fatty Liver Disease: Pathology and Pathogenesis
Tiniakos, D. G., Vos, M. B., & Brunt, E. M. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102132 · Cited by 870 · see citing works
Inflammatory mechanisms in the regulation of insulin resistance
Tilg, H., & Moschen, A. R. (2008) · Molecular Medicine · doi:10.2119/2007-00119.tilg · Cited by 779 · see citing works
The role of TNFα and TNF receptors in obesity and insulin resistance
Hotamisligil, G. S. (1999) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.1999.00490.x · Cited by 780 · see citing works
The expression of TNF alpha by human muscle. Relationship to insulin resistance.
Saghizadeh, M., Ong, J. M., Garvey, W. T., Henry, R. R., & Kern, P. A. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118504 · Cited by 717 · see citing works
Self-citationDefective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis.
Pérez-Carreras, M., Del Hoyo, P., Martín, M. A., Rubio, J. C., Martín, A., Castellano, G., Colina, F., Arenas, J., & Solis-Herruzo, J. A. (2003) · Hepatology · doi:10.1002/hep.1840380426 · Cited by 734 · see citing works
Schaap, L. A., Pluijm, S. M. F., Deeg, D. J. H., Harris, T. B., Kritchevsky, S. B., Newman, A. B., Colbert, L. H., Pahor, M., Rubin, S. M., Tylavsky, F. A., et al. (2009) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glp097 · Cited by 683 · see citing works
Kilroy, G. E., Foster, S. J., Wu, X., Ruiz, J., Sherwood, S., Heifetz, A., Ludlow, J. W., Stricker, D. M., Potiny, S., Green, P., et al. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21068 · Cited by 642 · see citing works
Obesity as a cardiovascular risk factor
Sowers, J. R. (2003) · The American Journal of Medicine · doi:10.1016/j.amjmed.2003.08.012 · Cited by 584 · see citing works
Stephens, J. M., Lee, J., & Pilch, P. F. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.2.971 · Cited by 553 · see citing works
Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-α
Ruan, H., & Lodish, H. F. (2003) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(03)00052-2 · Cited by 541 · see citing works
Pitteloud, N., Hardin, M., Dwyer, A. A., Valassi, E., Yialamas, M., Elahi, D., & Hayes, F. J. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-2190 · Cited by 525 · see citing works
Gut microbiome and liver diseases
Tilg, H., Cani, P. D., & Mayer, E. A. (2016) · Gut · doi:10.1136/gutjnl-2016-312729 · Cited by 525 · see citing works
Insulin resistance causes inflammation in adipose tissue
Shimobayashi, M., Albert, V., Woelnerhanssen, B., Frei, I. C., Weissenberger, D., Meyer-Gerspach, A. C., Clement, N., Moes, S., Colombi, M., Meier, J. A., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96139 · Cited by 480 · see citing works
Chronic Exposure to Interleukin-6 Causes Hepatic Insulin Resistance in Mice
Klover, P. J., Zimmers, T. A., Koniaris, L. G., & Mooney, R. A. (2003) · Diabetes · doi:10.2337/diabetes.52.11.2784 · Cited by 488 · see citing works
Cottam, D. R., Mattar, S. G., Barinas-Mitchell, E., Eid, G., Kuller, L., Kelley, D. E., & Schauer, P. R. (2004) · Obesity Surgery · doi:10.1381/096089204323093345 · Cited by 461 · see citing works
Resistance exercise decreases skeletal muscle tumor necrosis factor α in frail elderly humans
GREIWE, J. S., CHENG, B., RUBIN, D. C., YARASHESKI, K. E., & SEMENKOVICH, C. F. (2001) · The FASEB Journal · doi:10.1096/fj.00-0274com · Cited by 454 · see citing works
Innate immunity and inflammation in ageing: a key for understanding age-related diseases
Licastro, F., Candore, G., Lio, D., Porcellini, E., Colonna-Romano, G., Franceschi, C., & Caruso, C. (2005) · Immunity & Ageing · doi:10.1186/1742-4933-2-8 · Cited by 453 · see citing works
Pessayre, D., & Fromenty, B. (2005) · Journal of Hepatology · doi:10.1016/j.jhep.2005.03.004 · Cited by 441 · see citing works
Peraldi, P., Hotamisligil, G. S., Buurman, W. A., White, M. F., & Spiegelman, B. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.22.13018 · Cited by 412 · see citing works
Secretory factors from human adipose tissue and their functional role
Hauner, H. (2005) · Proceedings of the Nutrition Society · doi:10.1079/pns2005428 · Cited by 391 · see citing works
Aging, obesity, and inflammatory age-related diseases
Frasca, D., Blomberg, B. B., & Paganelli, R. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01745 · Cited by 371 · see citing works
Di Gregorio, G. B., Yao-Borengasser, A., Rasouli, N., Varma, V., Lu, T., Miles, L. M., Ranganathan, G., Peterson, C. A., McGehee, R. E., & Kern, P. A. (2005) · Diabetes · doi:10.2337/diabetes.54.8.2305 · Cited by 362 · see citing works
Self-citationHotamisligil, G. S. (2005) · Diabetes · doi:10.2337/diabetes.54.suppl_2.s73 · Cited by 352 · see citing works
Alessi, M. C., Bastelica, D., Morange, P., Berthet, B., Leduc, I., Verdier, M., Geel, O., & Juhan-Vague, I. (2000) · Diabetes · doi:10.2337/diabetes.49.8.1374 · Cited by 344 · see citing works
Adipogenesis and aging: does aging make fat go MAD
Kirkland, J. L., Tchkonia, T., Pirtskhalava, T., Han, J., & Karagiannides, I. (2002) · Experimental Gerontology · doi:10.1016/s0531-5565(02)00014-1 · Cited by 339 · see citing works
Metabolic syndrome is an inflammatory disorder: A conspiracy between adipose tissue and phagocytes
Reddy, P., Lent-Schochet, D., Ramakrishnan, N., McLaughlin, M., & Jialal, I. (2019) · Clinica Chimica Acta · doi:10.1016/j.cca.2019.06.019 · Cited by 297 · see citing works
Dominguez, H., Storgaard, H., Rask-Madsen, C., Steffen Hermann, T., Ihlemann, N., Baunbjerg Nielsen, D., Spohr, C., Kober, L., Vaag, A., & Torp-Pedersen, C. (2005) · Journal of Vascular Research · doi:10.1159/000088261 · Cited by 286 · see citing works
Obesity and cancer: existing and new hypotheses for a causal connection
Stone, T. W., McPherson, M., & Gail Darlington, L. (2018) · eBioMedicine · doi:10.1016/j.ebiom.2018.02.022 · Cited by 262 · see citing works
Nicklas, B. J. (2005) · Canadian Medical Association Journal · doi:10.1503/cmaj.1040769 · Cited by 259 · see citing works
Miyazawa-Hoshimoto, S., Takahashi, K., Bujo, H., Hashimoto, N., & Saito, Y. (2003) · Diabetologia · doi:10.1007/s00125-003-1221-6 · Cited by 254 · see citing works
Weight loss reduces interleukin-18 levels in obese women
Esposito, K., Pontillo, A., Ciotola, M., Di Palo, C., Grella, E., Nicoletti, G., & Giugliano, D. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.8.8781 · Cited by 254 · see citing works
Interplay between the immune system and adipose tissue in obesity
Exley, M. A., Hand, L., O'Shea, D., & Lynch, L. (2014) · Journal of Endocrinology · doi:10.1530/joe-13-0516 · Cited by 242 · see citing works
Khaodhiar, L., Ling, P., Blackburn, G. L., & Bistrian, B. R. (2004) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607104028006410 · Cited by 243 · see citing works
Neilson, H. K., Friedenreich, C. M., Brockton, N. T., & Millikan, R. C. (2009) · Cancer Epidemiology, Biomarkers & Prevention · doi:10.1158/1055-9965.epi-08-0756 · Cited by 232 · see citing works
Meydani, S. N., Das, S. K., Pieper, C. F., Lewis, M. R., Klein, S., Dixit, V. D., Gupta, A. K., Villareal, D. T., Bhapkar, M., Huang, M., et al. (2016) · Aging · doi:10.18632/aging.100994 · Cited by 228 · see citing works
The Metabolic Syndrome and Inflammation
Sutherland, J. P., McKinley, B., & Eckel, R. H. (2004) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2004.2.82 · Cited by 243 · see citing works
Obesity after spinal cord injury
Gater, D. R. (2007) · Physical Medicine and Rehabilitation Clinics of North America · doi:10.1016/j.pmr.2007.03.004 · Cited by 228 · see citing works
Samad, F., Uysal, K. T., Wiesbrock, S. M., Pandey, M., Hotamisligil, G. S., & Loskutoff, D. J. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.12.6902 · Cited by 226 · see citing works
The renin-angiotensin system and natriuretic peptides in obesity-associated hypertension
Engeli, S., & Sharma, A. M. (2001) · Journal of Molecular Medicine · doi:10.1007/s001090000144 · Cited by 225 · see citing works
The hematologic consequences of obesity
Purdy, J. C., & Shatzel, J. J. (2021) · European Journal Of Haematology · doi:10.1111/ejh.13560 · Cited by 227 · see citing works
YAMAMOTO, K., TAKESHITA, K., KOJIMA, T., TAKAMATSU, J., & SAITO, H. (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.11.013 · Cited by 214 · see citing works
Metabolic adaptation in obesity and type ii diabetes: myokines, adipokines and hepatokines
Oh, K.-J., Lee, D., Kim, W., Han, B., Lee, S., & Bae, K.-H. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms18010008 · Cited by 210 · see citing works
Dahlman, I., Forsgren, M., Sjögren, A., Nordström, E. A., Kaaman, M., Näslund, E., Attersand, A., & Arner, P. (2006) · Diabetes · doi:10.2337/db05-1421 · Cited by 184 · see citing works
You, T., Yang, R., Lyles, M. F., Gong, D., & Nicklas, B. J. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00419.2004 · Cited by 173 · see citing works
Marfella, R., Esposito, K., Siniscalchi, M., Cacciapuoti, F., Giugliano, F., Labriola, D., Ciotola, M., Di Palo, C., Misso, L., & Giugliano, D. (2004) · Diabetes Care · doi:10.2337/diacare.27.1.47 · Cited by 170 · see citing works
State of the Art Reviews: The Anti-Inflammatory Actions of Exercise Training
Flynn, M. G., McFarlin, B. K., & Markofski, M. M. (2007) · American Journal of Lifestyle Medicine · doi:10.1177/1559827607300283 · Cited by 154 · see citing works
Puig, K. L., Floden, A. M., Adhikari, R., Golovko, M. Y., & Combs, C. K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030378 · Cited by 152 · see citing works
Yudkin, J. S., Juhan-Vague, I., Hawe, E., Humphries, S. E., di Minno, G., Margaglione, M., Tremoli, E., Kooistra, T., Morange, P. E., Lundman, P., et al. (2004) · Metabolism · doi:10.1016/j.metabol.2004.02.004 · Cited by 153 · see citing works
Goren, I., Müller, E., Schiefelbein, D., Christen, U., Pfeilschifter, J., Mühl, H., & Frank, S. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700842 · Cited by 151 · see citing works
Body composition and mortality after adult lung transplantation in the United States
Singer, J. P., Peterson, E. R., Snyder, M. E., Katz, P. P., Golden, J. A., D’Ovidio, F., Bacchetta, M., Sonett, J. R., Kukreja, J., Shah, L., et al. (2014) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201405-0973oc · Cited by 133 · see citing works
Poppitt, S. D., Keogh, G. F., Lithander, F. E., Wang, Y., Mulvey, T. B., Chan, Y.-K., McArdle, B. H., & Cooper, G. J. S. (2008) · Nutrition · doi:10.1016/j.nut.2007.12.012 · Cited by 112 · see citing works
Somm, E., Cettour-Rose, P., Asensio, C., Charollais, A., Klein, M., Theander-Carrillo, C., Juge-Aubry, C. E., Dayer, J. M., Nicklin, M. J. H., Meda, P., et al. (2006) · Diabetologia · doi:10.1007/s00125-005-0046-x · Cited by 111 · see citing works
Adipose tissue as an endocrine organ
Prins, J. B. (2002) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1053/beem.2002.0222 · Cited by 121 · see citing works
Ageing, adipose tissue, fatty acids and inflammation
Pararasa, C., Bailey, C. J., & Griffiths, H. R. (2015) · Biogerontology · doi:10.1007/s10522-014-9536-x · Cited by 110 · see citing works
Adiponectin: a key fat-derived molecule regulating inflammation
Tilg, H., & Wolf, A. M. (2005) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.9.2.245 · Cited by 71 · see citing works
Association of inflammation with worsening HOMA-insulin resistance
Park, K., Steffes, M., Lee, D.-H., Himes, J. H., & Jacobs, D. R. (2009) · Diabetologia · doi:10.1007/s00125-009-1486-5 · Cited by 72 · see citing works
Bariatric surgery: remission of inflammation, cardiometabolic benefits, and common adverse effects
Biobaku, F., Ghanim, H., Monte, S. V., Caruana, J. A., & Dandona, P. (2020) · Journal of the Endocrine Society · doi:10.1210/jendso/bvaa049 · Cited by 68 · see citing works
Dangers, and benefits of the cytokine mediated response to injury and infection
Soeters, P. B., & Grimble, R. F. (2009) · Clinical Nutrition · doi:10.1016/j.clnu.2009.05.014 · Cited by 57 · see citing works
Lower frequency of daily teeth brushing is related to high prevalence of cardiovascular risk factors
Fujita, M., Ueno, K., & Hata, A. (2009) · Experimental Biology and Medicine · doi:10.3181/0809-rm-265 · Cited by 42 · see citing works
Murphy, J., Moullec, G., & Santosa, S. (2017) · Metabolism · doi:10.1016/j.metabol.2016.09.009 · Cited by 32 · see citing works
- Authors
- Kern, P. A., Saghizadeh, M., Ong, J. M., Bosch, R. J., Deem, R., & Simsolo, R. B.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1995-05-01
- Volume
- 95
- Issue
- 5
- Pages
- 2111-2119
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC295809
- OpenAlex
- W2066160102
- Cited by
- 1,305
- References
- 62
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 18 · 2023: 26 · 2022: 29 · 2021: 26 · 2020: 33 · 2019: 24 · 2018: 39 · 2017: 40 · 2016: 26 · 2015: 46 · 2014: 55 · 2013: 49 · 2012: 51
- FWCI
- 28.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Deutsches Krebsforschungszentrum
- Cedars-Sinai Medical Center
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 39176)
- National Center for Research Resources (RR00425, M01RR000425)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- TNF-α, adipose tissue, obesity, weight loss, lipoprotein lipase, adipocytes, body mass index, TNF mRNA expression, insulin resistance, adipose tissue inflammation, adipose tissue cytokines
- MeSH terms
- Adipose Tissue, Adult, Biopsy, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Female, Gene Expression Regulation, Humans, Lipoprotein Lipase, Male, Middle Aged, Obesity, Regression Analysis, RNA, Messenger, Tumor Necrosis Factor-alpha, Blotting, Northern, Weight Loss, Body Mass Index, Polymerase Chain Reaction, Adipocytes
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
