Abstract
The aim of this paper is to explore the effect of intestinal ischemia/reperfusion (I/R) injury on leptin and orexin-A levels in peripheral blood and central secretory tissues, and to examine the roles of leptin and orexin-A in acute inflammatory responses. An intestinal I/R injury model of rats was made; the rats were grouped according to the time of after 60 min ischemia. Radioimmunoassay was employed to detect the levels of leptin in serum and adipose tissue and orexin-A levels in plasma and hypothalamus. Reverse transcriptase-polymerase chain reaction was used to detect mRNA expressions of adipose leptin and hypothalamus orexin-A. Compared with the levels before the injury, serum leptin in 60 min ischemia/30 min reperfusion (I60′R30′) group decreased and that of I60′R360′ group increased. Compared with sham-operation group (sham group) after injury, serum leptin level of I60′R360′ group increased, adipose leptin levels of I60′R30′ and I60′R90′ decreased, and adipose leptin in I60′R360′ group increased. After the injury, adipose leptin mRNA expressions of I60′R30′, I60′R240′ and I60′R360′ increased, whereas that of I60′R150′ group decreased as compared with the sham group. There was no significant difference in the protein levels of orexin-A, either between plasma and hypothalamus or between pre-and post-I/R injury. Compared with sham group, hypothalamus orexin-A mRNA expressions of I60′R30′ and I60′R90′ decreased gradually after the injury, with that of I60′R150′ group reaching the lowest, and those of I60′R240′ and I60′R360′ recovering gradually, although they were still significantly lower than that of sham group. Leptin and orexin-A respond to intestinal I/R injury in a time-dependent manner, with leptin responding more quickly than orexin-A does, and both of them may contribute to the metabolic disorders in acute inflammation.
Similar content being viewed by others
References
Marti A, Novo F J, Martinez-Anso E, Zaratiegui M, Aguado M, Martinez J A. Leptin gene transfer into muscle increases lipolysis and oxygen consumption in white fat tissue in ob/ob mice. Biochem Biophys Res Commun, 1998, 246(3): 859–862
Fantuzzi G, Faggioni R. Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol, 2000, 68(4): 437–446
Sakurai T. Orexin a link between energy homeostasis and adaptive behaviour. Curr Opin Clin Nutr Metab Care, 2003, 6(4): 353–360
Wieland H A, Soll R M, Doods H N, Stenkamp D, Humaus R, Lammle B, Beck-Sickinger A G. The SK-N-MC cell line expresses an orexin binding site different from recombinant orexin 1-type receptor. Eur J Biochem, 2002, 269(4): 1128–1135
Yang J C, Wang Z W, Li C L, Lin J H, Liu X G, Ji Q X. Multiple organ injury at early stage of intestinal and hepatic ischemia-reperfusion in rats. Di Yi Jun Yi Da Xue Xue Bao, 2004, 24(2): 198–200
Chaldakov G N, Stankulov I S, Hristova M, Ghenev P I. Adipobiology of disease: adipokines and adipokine-targeted pharmacology. Curr Pharm Des, 2003, 9(12): 789–794
Komaki G, Matsumoto Y, Nishikata H, Kawai K, Nozaki T, Takii M, Sogawa H, Kubo C. Orexin-A and leptin change inversely in fasting non-obese subjects. Eur J Endocrinol, 2001, 144(6): 645–651
Zhu Y, Yamanaka A, Kunii K, Tsujino N, Goto K, Sakurai T. Orexin-mediated feeding behavior involves both leptin-sensitive and-insensitive pathways. Physiol Behav, 2002, 77(2–3): 251–257
Lin J, Yan G T, Wang L H, Hao X H, Zhang K, Xue H. Leptin fluctuates in intestinal ischemia-reperfusion injury as inflammatory cytokine. Peptides, 2004, 25(12): 2187–2193
Lin J, Yan G T, Hao X H, Zhang K, Wang L H, Xue H. Establishment and primary application of a highly-sensitive orexin-A radio-immunoassay. J Immunoassay Immunochem, 2004, 25(1): 45–55
Turnage R H, Kadesky K M, Bartula L, Guice K S, Oldham K T, Myers S I. Splanchnic PGI2 release and “no reflow” following intestinal reperfusion. J Surg Res, 1995, 58(6): 558–564
Arihara Z, Takahashi K, Murakami O, Totsune K, Sone M, Satoh F, Ito S, Mouri T. Immunoreactive orexin-A in human plasma. Peptides, 2001, 22(1): 139–142
Bradford M M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem, 1976, 72: 248–254
Jaworek J, Bonior J, Pierzchalski P, Tomaszewska R, Stachura J, Sendur R, Leja A, Jachimczak B, Konturek P C, Bielanski W, Pawlik W, Konturek S J. Leptin protects the pancreas from damage induced by caerulein overstimulation by modulating cytokine production. Pancreatology, 2002, 2(2): 89–99
Johren O, Neidert S J, Kummer M, Dendorfer A, Dominiak P. Prepro-orexin and orexin receptor mRNAs are differentially expressed in peripheral tissues of male and female rats. Endocrinology, 2001, 142(8): 3324–3331
Sun K, Liu Z S, Sun Q. Role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning. World J Gastroenterol, 2004, 10(13): 1934–1938
Kawada T, Yamazaki T, Akiyama T, Mori H, Inagaki M, Shishido T, Takaki H, Sugimachi M, Sunagawa K. Effects of brief ischaemia on myocardial acetylcholine and noradrenaline levels in anaesthetized cats. Auton Neurosci, 2002, 95(1–2): 37–42
Shibuya I, Utsunomiya K, Toyohira Y, Ueno S, Tsutsui M, Cheah T B, Ueta Y, Izumi F, Yanagihara N. Regulation of catecholamine synthesis by leptin. Ann N Y Acad Sci, 2002, 971: 522–527
Kawada Y, Ueno S, Asayama K, Tsutsui M, Utsunomiya K, Toyohira Y, Morisada N, Tanaka K, Shirahata A, Yanagihara N. Stimulation of catecholamine synthesis by orexin-A in bovine adrenal medullary cells through orexin receptor-1. Biochem Pharmacol, 2003, 66(1): 141–147
Wallace A M, Tucker P, Williams D M, Hughes I A, Ahmed S F. Short-term effects of prednisolone and dexamethasone on circulating concentrations of leptin and sex hormone-binding globulin in children being treated for acute lymphoblastic leukaemia. Clin Endocrinol (Oxf), 2003, 58(6): 770–776
Stricker-Krongrad A, Beck B. Modulation of hypothalamic hypocretin/orexin mRNA expression by glucocorticoids. Biochem Biophys Res Commun, 2002, 296(1): 129–133
Leininger M T, Portocarrero C P, Bidwell C A, Spurlock M E, Houseknecht K L. Leptin expression is reduced with acute endotoxemia in the pig: correlation with glucose, insulin, and insulin-like growth factor-1 (IGF-1). J Interferon Cytokine Res, 2000, 20(1): 99–106
Ouedraogo R, Naslund E, Kirchgessner A L. Glucose regulates the release of orexin-a from the endocrine pancreas. Diabetes, 2003, 52(1): 111–117
Eikelis N, Schlaich M, Aggarwal A, Kaye D, Esler M. Interactions between leptin and the human sympathetic nervous system. Hypertension, 2003, 41(5): 1072–1079
Van den Top M, Nolan M F, Lee K, Richardson P J, Buijs R M, Davies C H, Spanswick D. Orexins induce increased excitability and synchronisation of rat sympathetic preganglionic neurones. J Physiol, 2003, 549(Pt 3): 809–821
Najib S, Sanchez-Margalet V. Human leptin promotes survival of human circulating blood monocytes prone to apoptosis by activation of p42/44 MAPK pathway. Cell Immunol, 2002, 220(2): 143–149
Martin-Romero C, Santos-Alvarez J, Goberna R, Sanchez-Margalet V. Human leptin enhances activation and proliferation of human circulating T lymphocytes. Cell Immunol, 2000, 199(1): 15–24
Hosoi T, Okuma Y, Wada S, Nomura Y. Inhibition of leptin-induced IL-1 beta expression by glucocorticoids in the brain. Brain Res, 2003, 969(1–2): 95–101
Kazumi T, Kawaguchi A, Hirano T, Yoshino G. C-reactive protein in young, apparently healthy men: associations with serum leptin, QTc interval, and high-density lipoprotein-cholesterol. Metabolism, 2003, 52(9): 1113–1116
Madiehe A M, Mitchell T D, Harris R B. Hyperleptinemia and reduced TNF-alpha secretion cause resistance of db/db mice to endotoxin. Am J Physiol Regul Integr Comp Physiol, 2003, 284(3): R763–770
Faggioni R, Moser A, Feingold K R, Grunfeld C. Reduced leptin levels in starvation increase susceptibility to endotoxic shock. Am J Pathol, 2000, 156(5): 1781–1787
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Journal of Southern Medical University, 2006, 26(6): 719–724 [译自: 南方医科大学学报]
Rights and permissions
About this article
Cite this article
Lin, J., Yan, G., Gao, X. et al. Effect of intestinal ischemia/reperfusion injury on leptin and orexin-A levels. Front. Med. China 1, 87–92 (2007). https://doi.org/10.1007/s11684-007-0017-3
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11684-007-0017-3