Review Article

You have free access to this content

CB1 receptors: emerging evidence for central and peripheral mechanisms that regulate energy balance, metabolism, and cardiovascular health

  1. Daniela Cota*

Article first published online: 7 AUG 2007

DOI: 10.1002/dmrr.764

Issue

Diabetes/Metabolism Research and Reviews

Diabetes/Metabolism Research and Reviews

Volume 23, Issue 7, pages 507–517, October 2007

Additional Information

How to Cite

Cota, D. (2007), CB1 receptors: emerging evidence for central and peripheral mechanisms that regulate energy balance, metabolism, and cardiovascular health. Diabetes Metab. Res. Rev., 23: 507–517. doi: 10.1002/dmrr.764

Author Information

  1. Department of Psychiatry, Obesity Research Center, Genome Research Institute, University of Cincinnati, Cincinnati, OH, USA

*Department of Psychiatry, Obesity Research Center, Genome Research Institute, University of Cincinnati, 2170, East Galbraith Road, Cincinnati, OH 45237, USA.

Publication History

  1. Issue published online: 21 SEP 2007
  2. Article first published online: 7 AUG 2007
  3. Manuscript Accepted: 20 JUN 2007
  4. Manuscript Revised: 16 JUN 2007
  5. Manuscript Received: 19 JUN 2006

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (386K)

References

  • 1
    Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988–1994. Diabetes Care 1998; 21: 518–524.
  • 2
    Eyre H, Kahn R, Robertson RM. Preventing cancer, cardiovascular disease, and diabetes: a common agenda for the American Cancer Society, the American Diabetes Association, and the American Heart Association. Diabetes Care 2004; 27: 1812–1824.
  • 3
    Haffner SM, Mykkanen L, Festa A, Burke JP, Stern MP. Insulin-resistant prediabetic subjects have more atherogenic risk factors than insulin-sensitive prediabetic subjects: implications for preventing coronary heart disease during the prediabetic state. Circulation 2000; 101: 975–980.
  • 4
    Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature 2006; 444: 881–887.
  • 5
    Flegal KM, Graubard BI, Williamson DF, Gail MH. Excess deaths associated with underweight, overweight, and obesity. JAMA 2005; 293: 1861–1867.
  • 6
    National Institutes of Health. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. In NIH Publication, 2002.
  • 7
    Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature 2006; 444: 875–880.
  • 8
    Abel EL. Cannabis: effects on hunger and thirst. Behav Biol 1975; 15: 255–281.
  • 9
    Hollister LE. Hunger and appetite after single doses of marihuana, alcohol, and dextroamphetamine. Clin Pharmacol Ther 1971; 12: 44–49.
  • 10
    Gaoni Y, Mechoulam R. Isolation, structure, and partial synthesis of an active constituent of hashish. J Am Chem Soc 1964; 86: 1646–1647.
  • 11
    Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990; 346: 561–564.
  • 12
    Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993; 365: 61–65.
  • 13
    Elphick MR, Satou Y, Satoh N. The invertebrate ancestry of endocannabinoid signalling: an orthologue of vertebrate cannabinoid receptors in the urochordate Ciona intestinalis. Gene 2003; 302: 95–101.
  • 14
    Panikashvili D, Simeonidou C, Ben-Shabat S, et al. An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature 2001; 413: 527–531.
  • 15
    Pagotto U, Marsicano G, Cota D, Lutz B, Pasquali R. The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocr Rev 2006; 27: 73–100.
  • 16
    Rodriguez de Fonseca F, Del Arco I, Martin-Calderon JL, Gorriti MA, Navarro M. Role of the endogenous cannabinoid system in the regulation of motor activity. Neurobiol Dis 1998; 5: 483–501.
  • 17
    Cota D, Woods SC. The role of the endocanabinoid system in the regulation of energy metabolism. Curr Opin Endocrinol Diabetes 2005; 12: 338–351.
  • 18
    Di Marzo V, Matias I. Endocannabinoid control of food intake and energy balance. Nat Neurosci 2005; 8: 585–589.
  • 19
    Howlett AC, Barth F, Bonner TI, et al. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 2002; 54: 161–202.
  • 20
    Freund TF, Katona I, Piomelli D. Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 2003; 83: 1017–1066.
  • 21
    Di Marzo V, Melck D, Bisogno T, De Petrocellis L. Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action. Trends Neurosci 1998; 21: 521–528.
  • 22
    Mailleux P, Parmentier M, Vanderhaeghen JJ. Distribution of cannabinoid receptor messenger RNA in the human brain: an in situ hybridization histochemistry with oligonucleotides. Neurosci Lett 1992; 143: 200–204.
  • 23
    Herkenham M, Lynn AB, Johnson MR, et al. Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci 1991; 11: 563–583.
  • 24
    Breivogel CS, Childers SR. The functional neuroanatomy of brain cannabinoid receptors. Neurobiol Dis 1998; 5: 417–431.
  • 25
    Schlicker E, Kathmann M. Modulation of transmitter release via presynaptic cannabinoid receptors. Trends Pharmacol Sci 2001; 22: 565–572.
  • 26
    Croci T, Manara L, Aureggi G, et al. In vitro functional evidence of neuronal cannabinoid CB1 receptors in human ileum. Br J Pharmacol 1998; 125: 1393–1395.
    Direct Link:
  • 27
    Osei-Hyiaman D, DePetrillo M, Pacher P, et al. Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J Clin Invest 2005; 115: 1298–1305.
  • 28
    Liu YL, Connoley IP, Wilson CA, Stock MJ. Effects of the cannabinoid CB1 receptor antagonist SR141 716 on oxygen consumption and soleus muscle glucose uptake in Lep(ob)/Lep(ob) mice. Int J Obes (Lond) 2005; 29: 183–187.
  • 29
    Cota D, Marsicano G, Tschop M, et al. The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J Clin Invest 2003; 112: 423–431.
  • 30
    Bensaid M, Gary-Bobo M, Esclangon A, et al. The cannabinoid CB1 receptor antagonist SR141 716 increases Acrp30 mRNA expression in adipose tissue of obese fa/fa rats and in cultured adipocyte cells. Mol Pharmacol 2003; 63: 908–914.
  • 31
    Juan-Pico P, Fuentes E, Javier Bermudez-Silva F, et al. Cannabinoid receptors regulate Ca(2 + ) signals and insulin secretion in pancreatic beta-cell. Cell Calcium 2005; 39: 155–162.
  • 32
    Galiegue S, Mary S, Marchand J, et al. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem 1995; 232: 54–61.
    Direct Link:
  • 33
    Van Sickle MD, Duncan M, Kingsley PJ, et al. Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 2005; 310: 329–332.
  • 34
    Gong JP, Onaivi ES, Ishiguro H, et al. Cannabinoid CB2 receptors: immunohistochemical localization in rat brain. Brain Res 2006; 1071: 10–23.
  • 35
    Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992; 258: 1946–1949.
  • 36
    Mechoulam R, Ben-Shabat S, Hanus L, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 1995; 50: 83–90.
  • 37
    Hanus L, Abu-Lafi S, Fride E, et al. 2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor. Proc Natl Acad Sci U S A 2001; 98: 3662–3665.
  • 38
    Porter AC, Sauer JM, Knierman MD, et al. Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. J Pharmacol Exp Ther 2002; 301: 1020–1024.
  • 39
    Bisogno T, Melck D, Bobrov M, et al. N-acyl-dopamines: novel synthetic CB(1) cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo. Biochem J 2000; 351: 817–824.
  • 40
    Piomelli D. The molecular logic of endocannabinoid signalling. Nat Rev Neurosci 2003; 4: 873–884.
  • 41
    Dinh TP, Carpenter D, Leslie FM, et al. Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci U S A 2002; 99: 10819–10824.
  • 42
    Thomas EA, Cravatt BF, Danielson PE, Gilula NB, Sutcliffe JG. Fatty acid amide hydrolase, the degradative enzyme for anandamide and oleamide, has selective distribution in neurons within the rat central nervous system. J Neurosci Res 1997; 50: 1047–1052.
    Direct Link:
  • 43
    Gonsiorek W, Lunn C, Fan X, et al. Endocannabinoid 2-arachidonyl glycerol is a full agonist through human type 2 cannabinoid receptor: antagonism by anandamide. Mol Pharmacol 2000; 57: 1045–1050.
  • 44
    Sugiura T, Kodaka T, Nakane S, et al. Evidence that the cannabinoid CB1 receptor is a 2-arachidonoylglycerol receptor. Structure-activity relationship of 2-arachidonoylglycerol, ether-linked analogues, and related compounds. J Biol Chem 1999; 274: 2794–2801.
  • 45
    Sugiura T, Kondo S, Kishimoto S, et al. Evidence that 2-arachidonoylglycerol but not N-palmitoylethanolamine or anandamide is the physiological ligand for the cannabinoid CB2 receptor. Comparison of the agonistic activities of various cannabinoid receptor ligands in HL-60 cells. J Biol Chem 2000; 275: 605–612.
  • 46
    Bisogno T, Berrendero F, Ambrosino G, et al. Brain regional distribution of endocannabinoids: implications for their biosynthesis and biological function. Biochem Biophys Res Commun 1999; 256: 377–380.
  • 47
    Gomez R, Navarro M, Ferrer B, et al. A peripheral mechanism for CB1 cannabinoid receptor-dependent modulation of feeding. J Neurosci 2002; 22: 9612–9617.
  • 48
    Bojesen IN, Hansen HS. Binding of anandamide to bovine serum albumin. J Lipid Res 2003; 44: 1790–1794.
  • 49
    Koe BK, Milne GM, Weissman A, Johnson MR, Melvin LS. Enhancement of brain [3H]flunitrazepam binding and analgesic activity of synthetic cannabimimetics. Eur J Pharmacol 1985; 109: 201–212.
  • 50
    Kuster JE, Stevenson JI, Ward SJ, D'Ambra TE, Haycock DA. Aminoalkylindole binding in rat cerebellum: selective displacement by natural and synthetic cannabinoids. J Pharmacol Exp Ther 1993; 264: 1352–1363.
  • 51
    Mechoulam R, Feigenbaum JJ, Lander N, et al. Enantiomeric cannabinoids: stereospecificity of psychotropic activity. Experientia 1988; 44: 762–764.
  • 52
    Rinaldi-Carmona M, Barth F, Heaulme M, et al. SR141 716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett 1994; 350: 240–244.
  • 53
    Gatley SJ, Gifford AN, Volkow ND, Lan R, Makriyannis A. 123I-labeled AM251: a radioiodinated ligand which binds in vivo to mouse brain cannabinoid CB1 receptors. Eur J Pharmacol 1996; 307: 331–338.
  • 54
    Gatley SJ, Lan R, Volkow ND, et al. Imaging the brain marijuana receptor: development of a radioligand that binds to cannabinoid CB1 receptors in vivo. J Neurochem 1998; 70: 417–423.
    Direct Link:
  • 55
    Beltramo M, Stella N, Calignano A, et al. Functional role of high-affinity anandamide transport, as revealed by selective inhibition. Science 1997; 277: 1094–1097.
  • 56
    Kathuria S, Gaetani S, Fegley D, et al. Modulation of anxiety through blockade of anandamide hydrolysis. Nat Med 2003; 9: 76–81.
  • 57
    Brown JE, Kassouny M, Cross JK. Kinetic studies of food intake and sucrose solution preference by rats treated with low doses of delta9-tetrahydrocannabinol. Behav Biol 1977; 20: 104–110.
  • 58
    Williams CM, Rogers PJ, Kirkham TC. Hyperphagia in pre-fed rats following oral delta9-THC. Physiol Behav 1998; 65: 343–346.
  • 59
    Williams CM, Kirkham TC. Reversal of delta 9-THC hyperphagia by SR141 716 and naloxone but not dexfenfluramine. Pharmacol Biochem Behav 2002; 71: 333–340.
  • 60
    Williams CM, Kirkham TC. Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors. Psychopharmacology (Berl) 1999; 143: 315–317.
  • 61
    Hao S, Avraham Y, Mechoulam R, Berry EM. Low dose anandamide affects food intake, cognitive function, neurotransmitter and corticosterone levels in diet-restricted mice. Eur J Pharmacol 2000; 392: 147–156.
  • 62
    Verty AN, McGregor IS, Mallet PE. Consumption of high carbohydrate, high fat, and normal chow is equally suppressed by a cannabinoid receptor antagonist in non-deprived rats. Neurosci Lett 2004; 354: 217–220.
  • 63
    Colombo G, Agabio R, Diaz G, et al. Appetite suppression and weight loss after the cannabinoid antagonist SR 141 716. Life Sci 1998; 63: PL113–PL117.
  • 64
    Werner NA, Koch JE. Effects of the cannabinoid antagonists AM281 and AM630 on deprivation-induced intake in Lewis rats. Brain Res 2003; 967: 290–292.
  • 65
    Di Marzo V, Goparaju SK, Wang L, et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 2001; 410: 822–825.
  • 66
    Wiley JL, Burston JJ, Leggett DC, et al. CB1 cannabinoid receptor-mediated modulation of food intake in mice. Br J Pharmacol 2005; 145: 293–300.
    Direct Link:
  • 67
    Seeley RJ, Woods SC. Monitoring of stored and available fuel by the CNS: implications for obesity. Nat Rev Neurosci 2003; 4: 901–909.
  • 68
    Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature 2000; 404: 661–671.
  • 69
    Grill HJ, Kaplan JM. The neuroanatomical axis for control of energy balance. Front Neuroendocrinol 2002; 23: 2–40.
  • 70
    Jamshidi N, Taylor DA. Anandamide administration into the ventromedial hypothalamus stimulates appetite in rats. Br J Pharmacol 2001; 134: 1151–1154.
    Direct Link:
  • 71
    Gardner EL. Endocannabinoid signaling system and brain reward: emphasis on dopamine. Pharmacol Biochem Behav 2005; 81: 263–284.
  • 72
    Cota D, Tschop MH, Horvath TL, Levine AS. Cannabinoids, opioids and eating behavior: The molecular face of hedonism? Brain Res Rev 2006; 51: 85–107.
  • 73
    Kirkham TC, Williams CM, Fezza F, Di Marzo V. Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: stimulation of eating by 2-arachidonoyl glycerol. Br J Pharmacol 2002; 136: 550–557.
    Direct Link:
  • 74
    Koch JE. Delta(9)-THC stimulates food intake in Lewis rats: effects on chow, high-fat and sweet high-fat diets. Pharmacol Biochem Behav 2001; 68: 539–543.
  • 75
    Williams CM, Kirkham TC. Observational analysis of feeding induced by Delta9-THC and anandamide. Physiol Behav 2002; 76: 241–250.
  • 76
    Arnone M, Maruani J, Chaperon F, et al. Selective inhibition of sucrose and ethanol intake by SR 141 716, an antagonist of central cannabinoid (CB1) receptors. Psychopharmacology (Berl) 1997; 132: 104–106.
  • 77
    Chaperon F, Soubrie P, Puech AJ, Thiebot MH. Involvement of central cannabinoid (CB1) receptors in the establishment of place conditioning in rats. Psychopharmacology (Berl) 1998; 135: 324–332.
  • 78
    Blundell JE, Jebb S, Stubbs RJ, et al. Effect of rimonabant on energy intake, motivation to eat and body weight with or without hypocaloric diet: the REBA study. Obes Rev 2006; 7(Suppl. 2):104 (PP0021).
  • 79
    Scheen AJ, Finer N, Hollander P, et al. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet 2006; 368: 1660–1672.
  • 80
    Fattore L, Cossu G, Spano MS, et al. Cannabinoids and reward: interactions with the opioid system. Crit Rev Neurobiol 2004; 16: 147–158.
  • 81
    Jo YH, Chen YJ, Chua SC Jr, Talmage DA, Role LW. Integration of endocannabinoid and leptin signaling in an appetite-related neural circuit. Neuron 2005; 48: 1055–1066.
  • 82
    Tucci SA, Rogers EK, Korbonits M, Kirkham TC. The cannabinoid CB1 receptor antagonist SR141 716 blocks the orexigenic effects of intrahypothalamic ghrelin. Br J Pharmacol 2004; 143: 520–523.
    Direct Link:
  • 83
    Hilairet S, Bouaboula M, Carriere D, Le Fur G, Casellas P. Hypersensitization of the Orexin 1 receptor by the CB1 receptor: evidence for cross-talk blocked by the specific CB1 antagonist, SR141 716. J Biol Chem 2003; 278: 23731–23737.
  • 84
    Haj-Dahmane S, Shen R-Y. The wake-promoting peptide orexin-b inhibits glutamatergic transmission to dorsal raphe nucleus serotonin neurons through retrograde endocannabinoid signaling. J Neurosci 2005; 25: 896–905.
  • 85
    Poncelet M, Maruani J, Calassi R, Soubrie P. Overeating, alcohol and sucrose consumption decrease in CB1 receptor deleted mice. Neurosci Lett 2003; 343: 216–218.
  • 86
    Di S, Malcher-Lopes R, Halmos KC, Tasker JG. Nongenomic glucocorticoid inhibition via endocannabinoid release in the hypothalamus: a fast feedback mechanism. J Neurosci 2003; 23: 4850–4857.
  • 87
    Verty AN, McFarlane JR, McGregor IS, Mallet PE. Evidence for an interaction between CB1 cannabinoid and melanocortin MCR-4 receptors in regulating food intake. Endocrinology 2004; 145: 3224–3231.
  • 88
    Hermann H, Marsicano G, Lutz B. Coexpression of the cannabinoid receptor type 1 with dopamine and serotonin receptors in distinct neuronal subpopulations of the adult mouse forebrain. Neuroscience 2002; 109: 451–460.
  • 89
    Rowland NE, Mukherjee M, Robertson K. Effects of the cannabinoid receptor antagonist SR 141 716, alone and in combination with dexfenfluramine or naloxone, on food intake in rats. Psychopharmacology 2001; 159: 111–116.
  • 90
    Massa F, Storr M, Lutz B. The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract. J Mol Med 2005; 83: 944–954.
  • 91
    Burdyga G, Lal S, Varro A, et al. Expression of cannabinoid CB1 receptors by vagal afferent neurons is inhibited by cholecystokinin. J Neurosci 2004; 24: 2708–2715.
  • 92
    Ravinet Trillou C, Arnone M, Delgorge C, et al. Anti-obesity effect of SR141 716, a CB1 receptor antagonist, in diet-induced obese mice. Am J Physiol Regul Integr Comp Physiol 2003; 284: R345–R353.
  • 93
    Vickers SP, Webster LJ, Wyatt A, Dourish CT, Kennett GA. Preferential effects of the cannabinoid CB1 receptor antagonist, SR 141 716, on food intake and body weight gain of obese (fa/fa) compared to lean Zucker rats. Psychopharmacology (Berl) 2003; 167: 103–111.
  • 94
    Ravinet Trillou C, Delgorge C, Menet C, Arnone M, Soubrie P. CB1 cannabinoid receptor knockout in mice leads to leanness, resistance to diet-induced obesity and enhanced leptin sensitivity. Int J Obes Relat Metab Disord 2004; 28: 640–648.
  • 95
    Jbilo O, Ravinet-Trillou C, Arnone M, et al. The CB1 receptor antagonist rimonabant reverses the diet-induced obesity phenotype through the regulation of lipolysis and energy balance. FASEB J 2005; 19: 1567–1569.
  • 96
    Bermudez-Silva FJ, Sanchez-Vera I, Suarez J, et al. Role of cannabinoid CB(2) receptors in glucose homeostasis in rats. Eur J Pharmacol 2007; 565: 207–211.
  • 97
    Matias I, Gonthier MP, Orlando P, et al. Regulation, function, and dysregulation of endocannabinoids in models of adipose and beta-pancreatic cells and in obesity and hyperglycemia. J Clin Endocrinol Metab 2006; 91: 3171–3180.
  • 98
    Engeli S, Bohnke J, Feldpausch M, et al. Activation of the peripheral endocannabinoid system in human obesity. Diabetes 2005; 54: 2838–2843.
  • 99
    Bluher M, Engeli S, Kloting N, et al. Dysregulation of the peripheral and adipose tissue endocannabinoid system in human abdominal obesity. Diabetes 2006; 55: 3053–3060.
  • 100
    Côté M, Matias I, Lemieux I, et al. Circulating endocannabinoid levels, abdominal adiposity and related cardiometabolic risk factors in obese men. Int J Obes (Lond) 2007; 31(4): 692–699.
  • 101
    Monteleone P, Matias I, Martiadis V, et al. Blood levels of the endocannabinoid anandamide are increased in anorexia nervosa and in binge-eating disorder, but not in bulimia nervosa. Neuropsychopharmacology 2005; 30: 1216–1221.
  • 102
    Berger A, Crozier G, Bisogno T, et al. Anandamide and diet: inclusion of dietary arachidonate and docosahexaenoate leads to increased brain levels of the corresponding N-acylethanolamines in piglets. Proc Natl Acad Sci U S A 2001; 98: 6402–6406.
  • 103
    Sipe J, Waalen J, Gerber A, Beutler E. Overweight and obesity associated with a missense polymorphism in fatty acid amide hydrolase (FAAH). Int J Obes Relat Metab Disord 2005; 29: 755–759.
  • 104
    Chiang KP, Gerber AL, Sipe JC, Cravatt BF. Reduced cellular expression and activity of the P129T mutant of human fatty acid amide hydrolase: evidence for a link between defects in the endocannabinoid system and problem drug use. Hum Mol Genet 2004; 13: 2113–2119.
  • 105
    Siegfried Z, Kanyas K, Latzer Y, et al. Association study of cannabinoid receptor gene (CNR1) alleles and anorexia nervosa: differences between restricting and binging/purging subtypes. Am J Med Genet B Neuropsychiatr Genet 2004; 125: 126–130.
    Direct Link:
  • 106
    Despres JP, Golay A, Sjostrom L. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 2005; 353: 2121–2134.
  • 107
    Pi-Sunyer FX, Aronne LJ, Heshmati HM, Devin J, Rosenstock J. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA 2006; 295: 761–775.
  • 108
    Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rossner S. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 2005; 365: 1389–1397.
  • 109
    Wang Y, Rimm EB, Stampfer MJ, Willett WC, Hu FB. Comparison of abdominal adiposity and overall obesity in predicting risk of type 2 diabetes among men. Am J Clin Nutr 2005; 81: 555–563.
  • 110
    Poirier B, Bidouard JP, Cadrouvele C, et al. The anti-obesity effect of rimonabant is associated with an improved serum lipid profile. Diabetes Obes Metab 2005; 7: 65–72.
    Direct Link:
  • 111
    Hildebrandt AL, Kelly-Sullivan DM, Black SC. Antiobesity effects of chronic cannabinoid CB1 receptor antagonist treatment in diet-induced obese mice. Eur J Pharmacol 2003; 462: 125–132.
  • 112
    Yamauchi T, Kamon J, Minokoshi Y, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 2002; 8: 1288–1295.
  • 113
    Lihn AS, Pedersen SB, Richelsen B. Adiponectin: action, regulation and association to insulin sensitivity. Obes Rev 2005; 6: 13–21.
    Direct Link:
  • 114
    Côté M, Mauriege P, Bergeron J, et al. Adiponectinemia in visceral obesity: impact on glucose tolerance and plasma lipoprotein and lipid levels in men. J Clin Endocrinol Metab 2005; 90: 1434–1439.
  • 115
    Ouchi N, Kihara S, Funahashi T, et al. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation 2003; 107: 671–674.
  • 116
    Caballero AE. Endothelial dysfunction, inflammation, and insulin resistance: a focus on subjects at risk for type 2 diabetes. Curr Diab Rep 2004; 4: 237–246.
  • 117
    Ridker PM, Cannon CP, Morrow D, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005; 352: 20–28.
  • 118
    Tchernof A, Nolan A, Sites CK, Ades PA, Poehlman ET. Weight loss reduces C-reactive protein levels in obese postmenopausal women. Circulation 2002; 105: 564–569.
  • 119
    Kern PA, Di Gregorio GB, Lu T, Rassouli N, Ranganathan G. Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes 2003; 52: 1779–1785.
View Full Article (HTML) Get PDF (386K)