As part of the postsurgical stress response, plasma leptin levels increase in-between 12 h postoperatively. Objective: To study the kinetics of leptin gene expression in different adipose tissues before and after severe surgical trauma in children and adults. Methods: In 22 adults and 23 children with cardiac and 19 adult patients with abdominal surgery, we measured plasma leptin concentrations preoperatively, 4 and 10–17 h postoperatively and quantified leptin mRNA expression by TaqMan real-time PCR in adipose tissue taken at the beginning and the end of surgery from subcutaneous, intrathoracic, omental and mesenteric fat. Plasma-soluble leptin receptor levels were measured in 23 children after cardiosurgery. Results: Plasma leptin levels doubled between 4 and 10–17 h postoperatively in adults (p < 0.001) as well as in children (p = 0.0002) with cardiac surgery. After abdominal surgery, 10–17 h postoperatively, plasma leptin concentrations increased significantly (p < 0.05). During the operation, leptin gene expression did not change in neither of the patient groups. Plasma-soluble leptin receptor levels decreased immediately after the onset of surgery and remained unchanged thereafter. Conclusions: Leptin gene expression is not up-regulated during surgery. The measured increase in plasma leptin after surgery does not result from elevated levels of soluble leptin receptor but may follow an up-regulation of leptin gene expression later after the operation due to postsurgical metabolic changes.

1.
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM: Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425–432.
2.
Dötsch J, Nüsken KD, Knerr I, Kirschbaum M, Repp R, Rascher W: Leptin and neuropeptide Y gene expression in human placenta: Ontogeny and evidence for similarities to hypothalamic regulation. J Clin Endocrinol Metab 1999;84:2755–2758.
3.
Gröschl M, Rauh M, Wagner R, Neuhuber W, Metzler M, Tamgüney G, Zenk J, Schoof E, Dörr HG, Blum WF, Rascher W, Dötsch J: Identification of leptin in human saliva. J Clin Endocrinol Metab 2001;86:5234–5239.
4.
Bado A, Levasseur S, Attoub S, Kermorgant S, Laigneau JP, Bortoluzzi MN, Moizo L, Lehy T, Guerre-Millo M, Le Marchand-Brustel Y, Lewin MJ: The stomach is a source of leptin. Nature 1998;394:790–793.
5.
Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM: Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995;269:543–546.
6.
Bornstein SR: Is leptin a stress related peptide? Nat Med 1997;3:937.
7.
Kain ZN, Zimolo Z, Heninger G: Leptin and the perioperative neuroendocrinological stress response. J Clin Endocrinol Metab 1999;84:2438–2442.
8.
Dötsch J, Wagner R, Gröschl M, Schoof E, Harig F, Scharf J, Singer H, Katz N, Blum WF, Dörr HG, Rascher W: Cardiopulmonary bypass surgery does not further increase elevated serum leptin concentrations after major surgery. Pediatr Crit Care Med 2001;2:36–39.
9.
Stratton RJ, Dewit O, Crowe E, Jennings E, Villar RN, Elia N: Plasma leptin, energy expenditure and hunger following total hip replacement surgery. Clin Sci 1997;93:113–117.
10.
Modan-Moses D, Kanety H, Dagan O, Pariente C, Ben-Abraham R, Freedman L, Prince T, Shimon I, Barzilay Z, Paret G: Circulating leptin levels after cardiopulmonary bypass in children. J Cardiothorac Vasc Anesth 2001;15:740–744.
11.
Modan-Moses D, Ehrlich S, Kanety H, Dagan O, Pariente C, Esrahi N, Lotan D, Vishne T, Barzilay Z, Paret G: Circulating leptin and the perioperative neuroendocrinological stress response after pediatric cardiac surgery. Crit Care Med 2001;29:2377–2382.
12.
Yoshimitsu N, Duchi T, Nagata Y: Perioperative changes in circulating leptin levels in women undergoing total abdominal hysterectomy. Endocr J 2001;48:500–513.
13.
Bornstein SR, Preas HL, Chrousos GP, Suffredini AF: Circulating leptin levels during acute experimental endotoxinemia and anti-inflammatory therapy in humans. J Infect Dis 1998;178:887–890.
14.
Bornstein SR, Licinio J, Tauchnitz R, Engelmann L, Negrao AB, Gold P, Chrousos GP: Plasma leptin levels are increased in survivors of acute sepsis: associated loss of diurnal rhythm, in cortisol and leptin secretion. J Clin Endocrinol Metab 1998;83:280–283.
15.
Miell JP, Englaro P, Blum WF: Dexamethasone induces an acute and sustained rise in circulating leptin levels in normal human subjects. Horm Metab Res 1996;28:704–707.
16.
Wabitsch M, Jensen PB, Blum WF, Christoffersen CT, Englaro P, Heinze E, Rascher W, Teller W, Tornqvist H, Hauner H: Insulin and cortisol promote leptin production in cultured human fat cells. Diabetes 1996;45:1435–1438.
17.
Kristensen K, Pedersen SB, Richelsen B: Regulation of leptin by steroid hormones in rat adipose tissue. Biochem Biophys Res Commun 1999;259:624–630.
18.
Janik JE, Curti BD, Considine RV, Rager HC, Powers GC, Alvord WG, Smith JW 2nd, Gause BL, Kopp WC: Interleukin-1α increases serum leptin concentrations in humans. J Clin Endocrinol Metab 1997;82:3084–3086.
19.
Zumbach MS, Boehme MW, Wahl P, Stremmel W, Ziegler R, Nawroth PP: Tumor necrosis factor increases serum leptin levels in humans. J Clin Endocrinol Metab 1997;82:4080–4082.
20.
Casey WF, Hauser GJ, Hannallah RS Midgley FM, Khan WN: Circulating endotoxin and tumor necrosis factor during pediatric cardiac surgery. Crit Care Med 1992;20:1090–1096.
21.
Cremer J, Martin M, Redl H, Bahrami S, Abraham C, Graeter T, Haverich A, Schlag G, Borst HG: Systemic inflammatory response after cardiac operations. Ann Thorac Surg 1996;61:1714–1720.
22.
Lammert A, Kiess W, Bottner A, Glasow A, Kratzsch J: Soluble leptin receptor represents the main leptin binding activity in human blood. Biochem Biophys Res Commun 2001;283:982–988.
23.
Kratzsch J, Lammert A, Bottner A, Seidel B, Müller G, Thiery J, Hebebrand J, Kiess W: Circulating soluble leptin receptor and free leptin index during childhood, puberty and adolescence. J Clin Endocrinol Metab 2002;87:4587–4594.
24.
Chan JL, Bluher S, Yiannakouris N, Suchard MA, Kratzsch J, Mantzoros CS: Regulation of circulating soluble leptin receptor levels by gender, adiposity, sex steroids and leptin: Observational and interventional studies in humans. Diabetes 2002;51:2105–2112.
25.
Voegeling S, Fantuzzi G: Regulation of free and bound leptin and soluble leptin receptors during inflammation in mice. Cytokine 2001;14:97–103.
26.
Knerr I, Repp R, Dötsch J, Gratzki N, Hänze J, Kapellen T, Rascher W: Quantitation of gene expression by real-time PCR disproves a ‘retroviral hypothesis’ for childhood-onset diabetes mellitus. Pediatr Res 1999;46:57–60.
27.
Gröschl M, Wagner R, Dörr HG, Blum WF, Rascher W, Dötsch J: Variability of leptin values measured from different samples matrices. Horm Res 2000;54:26–31.
28.
Hernandez C, Simo R, Chacon P, Sabin P, Baena JA, Castellanos JM, Planas M: Influence of surgical stress and parenteral nutrition on serum leptin concentration. Clin Nutr 2000;19:61–64.
29.
Stangl K, Cascorbi I, Laule M, Stangl V, Vogt M, Ziemer S, Roots I, Wernecke K, Baumann G, Hauner H: Elevated serum leptin in patients with coronary heart disease: No association with the Trp64Arg polymorphism of the β3-adrenergic receptor. Int J Obes Relat Metab Disord 2000;24:369–375.
30.
Moses AGW, Dowidar N, Holloway B, Waddell I, Fearon KCH, Ross JA: Leptin and its relation to weight loss, ob gene expression and the acute-phase response in surgical patients. Br J Surg 2001;88:588–593.
31.
Takahashi N, Waelput W, Guisez Y: Leptin is an endogenous protective protein against the toxicity exerted by tumor necrosis factor. J Exp Med 1999;189:207–212.
32.
Hube F, Hauner H: The role of TNF-α in human adipose tissue: Prevention of weight gain at the expense of insulin resistance? Horm Metab Res 1999;31:626–631.
33.
Roth-Isigkeit A, Hasselbach L, Ocklitz E, Bruckner S, Ros A, Gehring H, Schmucker P, Rink L, Seyfarth M: Inter-individual differences in cytokine release in patients undergoing cardiac surgery with cardiopulmonary bypass. Clin Exp Immunol 2001;125:82–88.
34.
Grunfeld C, Zhao C, Fuller J, Pollak A, Moser A, Friedman J, Feingold KR: Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters. J Clin Invest 1996;97:2152–2157.
35.
Sarraf P, Frederich RC, Turner EM, Ma G, Jaskowiak NT, Rivet DJ, Flier JS, Lowell BB, Fraker DL, Alexander HR: Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia. J Exp Med 1997;185:171–175.
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