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Horm Metab Res 2013; 45(08): 581-585
DOI: 10.1055/s-0033-1334946
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Improvement of Obesity by Activation of I1-Imidazoline Receptors in High Fat Diet-fed Mice

H. H. Chung
1   Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
,
J.- T. Cheng
1   Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
2   Institute of Medical Science, College of Health Science, Chang Jung Christian University, Guei-Ren, Tainan City, Taiwan
› Author Affiliations
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Publication History

received 29 December 2012

accepted 05 February 2013

Publication Date:
20 March 2013 (online)

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Abstract

Imidazoline I1-receptor (I1R) is known to regulate the blood pressure, and rilmenidine, as the agonist, is used to treat hypertension in clinics. However, the role of I1R in obesity is still unclear. In the present study, we investigated the changes of obesity by activation of I1R in high fat diet (HFD)-fed mice. Chronic administration of rilmenidine into HFD-fed mice for 8 weeks significantly reduced body weight, which was reversed by efaroxan at the dose sufficient to block I1R. Also, rilmenidine significantly decreased the energy intake of HFD-fed mice. This reduction of energy intake was abolished by efaroxan at the same dosing for blockade of I1R. However, hypothalamic I1R protein expression in HFD-fed mice was markedly lower than that in normal chow-fed mice. In addition, epididymal white adipose tissue (eWAT) cell size in HFD-fed mice was decreased by rilmenidine via the activation of I1R. Moreover, effect of rilmenidine on appetite disappeared in db/db mice. Taken together, we suggest that rilmenidine can improve obesity in HFD-fed mice through an activation of I1R to ameliorate energy intake and eWAT accumulation.

Key words

energy intake - high fat diet-induced mice - hyperphagia - imidazoline I1-receptors
 

  • References

  • 1 Barness LA, Opitz JM, Gilbert-Barness E. Obesity: genetic, molecular, and environmental aspects. Am J Med Genet A 2007; 143A: 3016-3034
    CrossrefPubMedGoogle Scholar
  • 2 Haslam DW, James WP. Obesity. Lancet 2005; 366: 1197-1209
    CrossrefPubMedGoogle Scholar
  • 3 Lau DC, Douketis JD, Morrison KM, Hramiak IM, Sharma AM, Ur E. 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children [summary]. CMAJ 2007; 176: S1-S13
    PubMedGoogle Scholar
  • 4 Strychar I. Diet in the management of weight loss. CMAJ 2006; 174: 56-63
    CrossrefPubMedGoogle Scholar
  • 5 Miller GD. Improved nutrient intake in older obese adults undergoing a structured diet and exercise intentional weight loss program. J Nutr Health Aging 2010; 14: 461-466
    CrossrefPubMedGoogle Scholar
  • 6 MacLean PS, Higgins JA, Wyatt HR, Melanson EL, Johnson GC, Jackman MR, Giles ED, Brown IE, Hill JO. Regular exercise attenuates the metabolic drive to regain weight after long-term weight loss. Am J Physiol Regul Integr Comp Physiol 2009; 297: R793-R802
    CrossrefPubMedGoogle Scholar
  • 7 Ernsberger P, Friedman JE, Koletsky RJ. The I1-imidazoline receptor: from binding site to therapeutic target in cardiovascular disease. J Hypertens 1997; 15 (Suppl) S9-S23
    PubMedGoogle Scholar
  • 8 Koletsky RJ, Velliquette RA, Ernsberger P. The role of I(1)-imidazoline receptors and alpha(2)-adrenergic receptors in the modulation of glucose and lipid metabolism in the SHROB model of metabolic syndrome X. Ann N Y Acad Sci 2003; 1009: 251-261
    CrossrefPubMedGoogle Scholar
  • 9 Niu CS, Wu HT, Cheng KC, Lin KC, Chen CT, Cheng JT. A novel mechanism for decreasing plasma lipid level from imidazoline I-1 receptor activation in high fat diet-fed mice. Horm Metab Res 2011; 43: 458-463
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Dupuy O, Bauduceau B, Mayaudon H. Efficacy of rilmenidine, a selective I1 imidazoline receptor binding agent in diabetic hypertensive patients. Am J Hypertens 2000; 13: 123S-126S
    PubMedGoogle Scholar
  • 11 Meredith PA, Reid JL. Efficacy and tolerability of long-term rilmenidine treatment in hypertensive diabetic patients. A retrospective analysis of a general practice study. Am J Cardiovasc Drugs 2004; 4: 195-200
    CrossrefPubMedGoogle Scholar
  • 12 Velliquette RA, Kossover R, Previs SF, Ernsberger P. Lipid-lowering actions of imidazoline antihypertensive agents in metabolic syndrome X. Naunyn Schmiedebergs Arch Pharmacol 2006; 372: 300-312
    CrossrefPubMedGoogle Scholar
  • 13 Yang PS, Wu HT, Chung HH, Chen CT, Chi CW, Yeh CH, Cheng JT. Rilmenidine improves hepatic steatosis through p38-dependent pathway to higher the expression of farnesoid X receptor. Naunyn Schmiedebergs Arch Pharmacol 2012; 385: 51-56
    CrossrefPubMedGoogle Scholar
  • 14 Chung HH, Yang TT, Chen MF, Chou MT, Cheng JT. Improvement of hyperphagia by activation of cerebral I(1)-imidazoline receptors in streptozotocin-induced diabetic mice. Horm Metab Res 2012; 44: 645-649
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Gongadze NV, Antelava NA, Kezeli TD. Imidazoline receptors. Georgian Med News 2008; 44-47
    PubMedGoogle Scholar
  • 16 Head GA, Mayorov DN. Imidazoline receptors, novel agents and therapeutic potential. Cardiovasc Hematol Agents Med Chem 2006; 4: 17-32
    CrossrefPubMedGoogle Scholar
  • 17 Head GA, Burke SL, Chan CK. Site and receptors involved in the sympathoinhibitory actions of rilmenidine. J Hypertens 1998; 16 (Suppl) S7-S12
    PubMedGoogle Scholar
  • 18 Ko WC, Liu IM, Chung HH, Cheng JT. Activation of I(2)-imidazoline receptors may ameliorate insulin resistance in fructose-rich chow-fed rats. Neurosci Lett 2008; 448: 90-93
    CrossrefPubMedGoogle Scholar
  • 19 Su CH, Liu IM, Chung HH, Cheng JT. Activation of I2-imidazoline receptors by agmatine improved insulin sensitivity through two mechanisms in type-2 diabetic rats. Neurosci Lett 2009; 457: 125-128
    CrossrefPubMedGoogle Scholar
  • 20 Yang TT, Ku PM, Hsu CT, Chung HH, Lee WJ, Cheng JT. Mediation of AMP Kinase in the Increase of Glucose Uptake in L6 Cells Induced by Activation of Imidazoline I-2 Receptors. Horm Metab Res 2012; Dec 7. [Epub ahead of print]
    PubMedGoogle Scholar
  • 21 Morgan NG, Chan SL. Imidazoline binding sites in the endocrine pancreas: can they fulfil their potential as targets for the development of new insulin secretagogues?. Curr Pharm Des 2001; 7: 1413-1431
    CrossrefPubMedGoogle Scholar
  • 22 Anderson NJ, Lupo PA, Nutt DJ, Hudson AL, Robinson ES. Characterisation of imidazoline I2 binding sites in pig brain. Eur J Pharmacol 2005; 519: 68-74
    CrossrefPubMedGoogle Scholar
  • 23 Thomas AJ, Erokwu BO, Yamamoto BK, Ernsberger P, Bishara O, Strohl KP. Alterations in respiratory behavior, brain neurochemistry and receptor density induced by pharmacologic suppression of sleep in the neonatal period. Brain Res Dev Brain Res 2000; 120: 181-189
    CrossrefPubMedGoogle Scholar
  • 24 Zhang J, Abdel-Rahman AA. Mitogen-activated protein kinase phosphorylation in the rostral ventrolateral medulla plays a key role in imidazoline (i1)-receptor-mediated hypotension. J Pharmacol Exp Ther 2005; 314: 945-952
    CrossrefPubMedGoogle Scholar
  • 25 El-Mas MM, El-Gowelli HM, Ghazal AR, Harraz OF, Mohy El-Din MM. Facilitation of central imidazoline I(1)-site/extracellular signal-regulated kinase/p38 mitogen-activated protein kinase signalling mediates the hypotensive effect of ethanol in rats with acute renal failure. Br J Pharmacol 2009; 158: 1629-1640
    CrossrefPubMedGoogle Scholar
  • 26 El-Mas MM, Abdel-Rahman AA. Evidence for the involvement of central I1 imidazoline receptor in ethanol counteraction of clonidine hypotension in spontaneously hypertensive rats. J Cardiovasc Pharmacol 2001; 38: 417-426
    CrossrefPubMedGoogle Scholar
  • 27 Bing C, King P, Pickavance L, Brown M, Ziegler D, Kaan E, Williams G. The effect of moxonidine on feeding and body fat in obese Zucker rats: role of hypothalamic NPY neurones. Br J Pharmacol 1999; 127: 35-42
    CrossrefPubMedGoogle Scholar
  • 28 Sato C, Shikata K, Hirota D, Sasaki M, Nishishita S, Miyamoto S, Kodera R, Ogawa D, Tone A, Kataoka HU, Wada J, Kajitani N, Makino H. P-selectin glycoprotein ligand-1 deficiency is protective against obesity-related insulin resistance. Diabetes 2011; 60: 189-199
    CrossrefPubMedGoogle Scholar
  • 29 Gautron L, Elmquist JK. Sixteen years and counting: an update on leptin in energy balance. J Clin Invest 2011; 121: 2087-2093
    CrossrefPubMedGoogle Scholar
  • 30 Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro JF. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334: 292-295
    CrossrefPubMedGoogle Scholar
  • 31 Varela L, Horvath TL. Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis. EMBO Rep 2012; 13: 1079-1086
    CrossrefPubMedGoogle Scholar
  • 32 Glavas MM, Kirigiti MA, Xiao XQ, Enriori PJ, Fisher SK, Evans AE, Grayson BE, Cowley MA, Smith MS, Grove KL. Early overnutrition results in early-onset arcuate leptin resistance and increased sensitivity to high-fat diet. Endocrinology 2010; 151: 1598-1610
    CrossrefPubMedGoogle Scholar
  • 33 Veniant MM, LeBel CP. Leptin: from animals to humans. Curr Pharm Des 2003; 9: 811-818
    CrossrefPubMedGoogle Scholar
  • 34 Sanjuliani AF, de Abreu VG, Francischetti EA. Selective imidazoline agonist moxonidine in obese hypertensive patients. Int J Clin Pract 2006; 60: 621-629
    CrossrefPubMedGoogle Scholar
  • 35 Jequier E. Leptin signaling, adiposity, and energy balance. Ann N Y Acad Sci 2002; 967: 379-388
    PubMedGoogle Scholar
  • 36 Guan XM, Yu H, Trumbauer M, Frazier E, Van der Ploeg LH, Chen H. Induction of neuropeptide Y expression in dorsomedial hypothalamus of diet-induced obese mice. Neuroreport 1998; 9: 3415-3419
    CrossrefPubMedGoogle Scholar
  • 37 Fellmann L, Nascimento AR, Tibiriça E, Bousquet P. Murine models for pharmacological studies of the metabolic syndrome. Pharmacol Ther 2013; 137: 331-340
    CrossrefPubMedGoogle Scholar
  • 38 Bergen HT, Mizuno TM, Taylor J, Mobbs CV. Hyperphagia and weight gain after gold-thioglucose: relation to hypothalamic neuropeptide Y and proopiomelanocortin. Endocrinology 1998; 139: 4483-4488
    CrossrefPubMedGoogle Scholar
  • 39 Zammaretti F, Panzica G, Eva C. Fasting, leptin treatment, and glucose administration differentially regulate Y(1) receptor gene expression in the hypothalamus of transgenic mice. Endocrinology 2001; 142: 3774-3782
    CrossrefPubMedGoogle Scholar
  • 40 Volkoff H, Eykelbosh AJ, Peter RE. Role of leptin in the control of feeding of goldfish Carassius auratus: interactions with cholecystokinin, neuropeptide Y and orexin A, and modulation by fasting. Brain Res 2003; 972: 90-109
    CrossrefPubMedGoogle Scholar
  • 41 Xu B, Kalra PS, Farmerie WG, Kalra SP. Daily changes in hypothalamic gene expression of neuropeptide Y, galanin, proopiomelanocortin, and adipocyte leptin gene expression and secretion: effects of food restriction. Endocrinology 1999; 140: 2868-2875
    CrossrefPubMedGoogle Scholar
  • 42 Wang JH, Wang F, Yang MJ, Yu DF, Wu WN, Liu J, Ma LQ, Cai F, Chen JG. Leptin regulated calcium channels of neuropeptide Y and proopiomelanocortin neurons by activation of different signal pathways. Neuroscience 2008; 156: 89-98
    CrossrefPubMedGoogle Scholar
  • 43 Arora S Anubhuti Role of neuropeptides in appetite regulation and obesity – a review. Neuropeptides 2006; 40: 375-401
    CrossrefPubMedGoogle Scholar