{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:52:41Z","timestamp":1792173161101,"version":"4.4.0"},"reference-count":83,"publisher":"Cambridge University Press (CUP)","issue":"3","license":[{"start":{"date-parts":[[2007,3,5]],"date-time":"2007-03-05T00:00:00Z","timestamp":1173052800000},"content-version":"unspecified","delay-in-days":2042,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proc. Nutr. Soc."],"published-print":{"date-parts":[[2001,8]]},"abstract":"<jats:p>\n                    Cytokines appear to be major regulators of adipose tissue metabolism. Therapeutic modulation of cytokine systems offers the possibility of major changes in adipose tissue behaviour. Cytokines within adipose tissue originate from adipocyte, preadipocyte and other cell types. mRNA expression studies show that adipocytes can synthesise both tumour necrosis factor a (TNF-a) and several interleukins (IL), notably IL-1b and IL-6. Other adipocyte products with \u2018immunological\u2019 actions include complement system products and macrophage colony-stimulating factor. Cytokine secretion within adipocytes appears similar to that of other cells. There is general agreement that circulating TNF-a and IL-6 concentrations are mildly elevated in obesity. Most studies suggest increased TNF-a mRNA expression or secretion\n                    <jats:italic>in vitro<\/jats:italic>\n                    in adipose tissue from obese subjects. The factors regulating cytokine release within adipose tissue appear to include usual \u2018inflammatory\u2018 stimuli such as lipopolysaccaride, but also the size of the fat cells\n                    <jats:italic>per se<\/jats:italic>\n                    and catecholamines. There is conflicting data about whether insulin and cortisol regulate TNF-a. The effects of cytokines within adipose tissue include some actions that might be characterised as metabolic. TNF-a and IL-6 inhibit lipoprotein lipase, and TNF-a additionally stimulates hormone-sensitive lipase and induces uncoupling protein expression. TNF-a also down regulates insulin-stimulated glucose uptake via effects on glucose transporter 4, insulin receptor autophosphorylation and insulin receptor substrate-1. All these effects will tend to reduce lipid accumulation within adipose tissue. Other effects appear more \u2018trophic\u2019, and include the induction of apoptosis, regulation of cell size and induction of de-differentiation (the latter involving reduced peroxisome proliferator-activated receptor g). Cytokines are important stimulators and repressors of other cytokines. In addition, cytokines appear to modulate other regulatory systems. Examples of the latter include effects on leptin secretion (probably stimulation followed by inhibition) and reduction of b\n                    <jats:sub>3<\/jats:sub>\n                    -adrenoceptor expression. There seems to be no clear agreement as to which cytokines derived from adipose tissue act as remote regulators, i.e. hormones. Leptin, which is structurally a cytokine, is also a hormone. IL-6 appears to be released systemically by adipose tissue, but TNF-a is probably not. Both leptin and IL-6 appear to act on the hypothalamus, IL-6 acts on the liver, while leptin may have actions on the pancreas. The importance of the immune system in whole-body energy balance provides a rationale for the links between cytokines and adipose tissue. It seems clear that TNF-a is a powerful autocrine and paracrine regulator of adipose tissue. Other cytokines, notably leptin, and possibly IL-6, have lesser actions on adipose tissue. These cytokines act as hormones, reporting the state of adipose tissue stores throughout the body.\n                  <\/jats:p>","DOI":"10.1079\/pns2001110","type":"journal-article","created":{"date-parts":[[2008,9,29]],"date-time":"2008-09-29T13:41:44Z","timestamp":1222695704000},"page":"349-356","source":"Crossref","is-referenced-by-count":809,"title":["Pro-inflammatory cytokines and adipose tissue"],"prefix":"10.1017","volume":"60","author":[{"given":"Simon W.","family":"Coppack","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2007,3,5]]},"reference":[{"key":"S0029665101000386_ref060","doi-asserted-by":"publisher","DOI":"10.1079\/PNS200198"},{"key":"S0029665101000386_ref028","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199904)179:1<58::AID-JCP8>3.0.CO;2-1"},{"key":"S0029665101000386_ref070","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0090061"},{"key":"S0029665101000386_ref012","first-page":"4113","article-title":"Interleukin 6 reduces lipoprotein lipase activity in adipose tissue of mice in vivo and in 3T3-L 1 adipocytes: a possible role for interleukin 6 in cancer cachexia","volume":"52","author":"Greenberg","year":"1992","journal-title":"Cancer Research"},{"key":"S0029665101000386_ref001","first-page":"3338","article-title":"Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss","volume":"85","author":"Bastard","year":"2000","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"S0029665101000386_ref054","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.9.2743"},{"key":"S0029665101000386_ref058","doi-asserted-by":"publisher","DOI":"10.1016\/S0899-9007(00)00413-5"},{"key":"S0029665101000386_ref052","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(89)90246-4"},{"key":"S0029665101000386_ref053","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-128-2-199801150-00009"},{"key":"S0029665101000386_ref020","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117495"},{"key":"S0029665101000386_ref014","doi-asserted-by":"publisher","DOI":"10.1097\/00041433-199405030-00008"},{"key":"S0029665101000386_ref080","doi-asserted-by":"publisher","DOI":"10.2337\/diab.46.9.1526"},{"key":"S0029665101000386_ref067","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.1.171"},{"key":"S0029665101000386_ref017","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.1999.00490.x"},{"key":"S0029665101000386_ref036","first-page":"1583","article-title":"Tumor necrosis factor is delivered to mitochondria where a tumor necrosis factor-binding protein is localised","volume":"78","author":"Ledgerwood","year":"1998","journal-title":"Laboratory Investigation"},{"key":"S0029665101000386_ref064","doi-asserted-by":"publisher","DOI":"10.1046\/j.1525-1373.2000.22318.x"},{"key":"S0029665101000386_ref021","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5291.1377"},{"key":"S0029665101000386_ref061","doi-asserted-by":"publisher","DOI":"10.2337\/diab.46.12.1939"},{"key":"S0029665101000386_ref016","doi-asserted-by":"publisher","DOI":"10.1007\/s001250050350"},{"key":"S0029665101000386_ref040","first-page":"E971","article-title":"Production of soluble tumor necrosis factor receptors by human subcutaneous adipose tissue in vivo","volume":"277","author":"Mohamed-Ali","year":"1999","journal-title":"American Journal of Physiology"},{"key":"S0029665101000386_ref003","doi-asserted-by":"publisher","DOI":"10.1126\/science.3754653"},{"key":"S0029665101000386_ref081","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(99)00463-3"},{"key":"S0029665101000386_ref055","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.22.13018"},{"key":"S0029665101000386_ref069","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1630033"},{"key":"S0029665101000386_ref042","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0800770"},{"key":"S0029665101000386_ref043","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.47.9.1384"},{"key":"S0029665101000386_ref031","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.17.9895"},{"key":"S0029665101000386_ref059","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7827(99)00003-X"},{"key":"S0029665101000386_ref073","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(96)80011-3"},{"key":"S0029665101000386_ref082","first-page":"1457","article-title":"Negative regulation of peroxisome proliferator-activated receptor-g gene expression contributes to the antiadipogenic effects of tumor necrosis factor-\u03b1","volume":"10","author":"Zhang","year":"1996","journal-title":"Molecular Endocrinology"},{"key":"S0029665101000386_ref071","doi-asserted-by":"crossref","first-page":"21839","DOI":"10.1016\/S0021-9258(18)54714-1","article-title":"Transcriptional regression of the GLUT4 and C\/EBP genes in 3T3-L1 adipocytes by tumor necrosis factor-alpha","volume":"266","author":"Stephens","year":"1991","journal-title":"Journal of Biological Chemistry"},{"key":"S0029665101000386_ref065","first-page":"1","article-title":"CNS regulation of thermogenesis","volume":"8","author":"Rothwell","year":"1994","journal-title":"Critical Reviews in Neurobiology"},{"key":"S0029665101000386_ref034","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119824"},{"key":"S0029665101000386_ref019","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117936"},{"key":"S0029665101000386_ref047","doi-asserted-by":"publisher","DOI":"10.2337\/diab.47.8.1365"},{"key":"S0029665101000386_ref083","doi-asserted-by":"publisher","DOI":"10.1038\/372425a0"},{"key":"S0029665101000386_ref029","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-4666(05)80001-8"},{"key":"S0029665101000386_ref078","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/39335","article-title":"Protection from obesity-induced insulin resistance in mice lacking TNF-\u03b1 function","volume":"389","author":"Uysal","year":"1997","journal-title":"Nature"},{"key":"S0029665101000386_ref077","doi-asserted-by":"publisher","DOI":"10.1210\/endo.139.12.6337"},{"key":"S0029665101000386_ref004","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.34.21120"},{"key":"S0029665101000386_ref022","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5249.665"},{"key":"S0029665101000386_ref026","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-978754"},{"key":"S0029665101000386_ref066","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/S0022-2275(20)32574-8","article-title":"Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period","volume":"39","author":"Saleh","year":"1998","journal-title":"Journal of Lipid Research"},{"key":"S0029665101000386_ref062","doi-asserted-by":"publisher","DOI":"10.1042\/cs0920003"},{"key":"S0029665101000386_ref013","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118653"},{"key":"S0029665101000386_ref063","first-page":"3052","article-title":"Aromatase activity and interleukin-6 production by normal and malignant breast tissues","volume":"80","author":"Purohit","year":"1995","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"S0029665101000386_ref072","doi-asserted-by":"publisher","DOI":"10.1016\/1043-4666(93)90058-D"},{"key":"S0029665101000386_ref023","doi-asserted-by":"publisher","DOI":"10.1126\/science.7678183"},{"key":"S0029665101000386_ref046","doi-asserted-by":"crossref","first-page":"5198","DOI":"10.4049\/jimmunol.155.11.5198","article-title":"A metalloproteinase inhibitor blocks shedding of the IL-6 receptor and the p60 tumor necrosis factor receptor","volume":"155","author":"Mullberg","year":"1995","journal-title":"Journal of Immunology"},{"key":"S0029665101000386_ref007","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1016\/S0022-2275(20)41334-3","article-title":"Endotoxin rapidly induces changes in lipid metabolism that produce hypertriglyceridemia: low doses stimulate hepatic triglyceride production while high doses inhibit clearance","volume":"33","author":"Feingold","year":"1992","journal-title":"Journal of Lipid Research"},{"key":"S0029665101000386_ref009","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1016\/S0022-2275(20)38211-0","article-title":"Cachectin\/tumor necrosis factor decreases human adipose tissue lipoprotein lipase mRNA levels, synthesis, and activity","volume":"30","author":"Fried","year":"1989","journal-title":"Journal of Lipid Research"},{"key":"S0029665101000386_ref037","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.47.4.515"},{"key":"S0029665101000386_ref025","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-978810"},{"key":"S0029665101000386_ref035","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-978671"},{"key":"S0029665101000386_ref045","first-page":"B190","article-title":"Adipose tissue-derived tumor necrosis factor-alpha activity is elevated in older rats","volume":"52","author":"Morin","year":"1997","journal-title":"Journal of Gerontology"},{"key":"S0029665101000386_ref057","first-page":"742","article-title":"Tumor necrosis factor-alpha prevents the differentiation of human adipocyte precursor cells and causes delipidation of newly developed fat cells","volume":"76","author":"Petruschke","year":"1993","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"S0029665101000386_ref005","first-page":"530","article-title":"Tumor necrosis factor-a inhibits leptin production in subcutaneous and omental adipocytes from morbidly obese humans","volume":"85","author":"Fawcett","year":"2000","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"S0029665101000386_ref015","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0800773"},{"key":"S0029665101000386_ref032","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.3.912"},{"key":"S0029665101000386_ref079","first-page":"E457","article-title":"TNF mimics the metabolic response of acute infections in healthy humans","volume":"261","author":"Van der Poll","year":"1991","journal-title":"American Journal of Physiology"},{"key":"S0029665101000386_ref038","article-title":"TNF and TNFR biology in health and disease","author":"McDermott","year":"2001","journal-title":"Cellular and Molecular Biology"},{"key":"S0029665101000386_ref018","doi-asserted-by":"publisher","DOI":"10.2337\/diab.46.3.451"},{"key":"S0029665101000386_ref041","first-page":"4196","article-title":"Subcutaneous adipose tissue secretes interleukin-6 but not tumour necrosis factor-a in vivo","volume":"82","author":"Mohamed-Ali","year":"1997","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"S0029665101000386_ref024","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.1999.00520.x"},{"key":"S0029665101000386_ref030","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1994.tb02502.x"},{"key":"S0029665101000386_ref044","doi-asserted-by":"publisher","DOI":"10.1210\/endo.138.11.5519"},{"key":"S0029665101000386_ref048","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1670165"},{"key":"S0029665101000386_ref033","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117899"},{"key":"S0029665101000386_ref010","doi-asserted-by":"publisher","DOI":"10.1038\/35007504"},{"key":"S0029665101000386_ref011","doi-asserted-by":"publisher","DOI":"10.1038\/370555a0"},{"key":"S0029665101000386_ref074","doi-asserted-by":"publisher","DOI":"10.3164\/jcbn.22.1"},{"key":"S0029665101000386_ref006","doi-asserted-by":"publisher","DOI":"10.2337\/diab.41.2.S97"},{"key":"S0029665101000386_ref051","doi-asserted-by":"publisher","DOI":"10.2337\/diab.45.7.881"},{"key":"S0029665101000386_ref056","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119715"},{"key":"S0029665101000386_ref002","first-page":"E992","article-title":"Endotoxin-induced alteration in the expression of leptin and b3-adrenergic receptor in adipose tissue","volume":"274","author":"Berkowitz","year":"1998","journal-title":"American Journal of Physiology"},{"key":"S0029665101000386_ref027","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2571(97)00007-1"},{"key":"S0029665101000386_ref049","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.14.8033"},{"key":"S0029665101000386_ref050","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.3.319"},{"key":"S0029665101000386_ref075","doi-asserted-by":"publisher","DOI":"10.1210\/endo.136.4.7895657"},{"key":"S0029665101000386_ref076","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.108.3.1105"},{"key":"S0029665101000386_ref068","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01250-3"},{"key":"S0029665101000386_ref008","first-page":"847","article-title":"Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot differences and regulation by glucocorticoid","volume":"83","author":"Fried","year":"1998","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"S0029665101000386_ref039","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.1998.0442"}],"container-title":["Proceedings of the Nutrition Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0029665101000386","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T22:49:53Z","timestamp":1709246993000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0029665101000386\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,8]]},"references-count":83,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2001,8]]}},"alternative-id":["S0029665101000386"],"URL":"https:\/\/doi.org\/10.1079\/pns2001110","relation":{},"ISSN":["0029-6651","1475-2719"],"issn-type":[{"value":"0029-6651","type":"print"},{"value":"1475-2719","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,8]]}}}