The American Journal of Medicine
Volume 120, Issue 9, Supplement 1 , Pages S18-S24 , September 2007

Understanding Metabolic Homeostasis and Imbalance: What Is the Role of the Endocannabinoid System?

  • George Kunos, MD, PhD

      Affiliations

    • Corresponding Author InformationRequests for reprints should be addressed to George Kunos, MD, PhD, National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), 6606 Marywood Road, Bethesda, Maryland 20817.

References 

  1. Cota D, Marsicano G, Tschöp M, et al. The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J Clin Invest. 2003;112:423–431
  2. Abel EL. Cannabis: effects on hunger and thirst. Behav Biol. 1975;15:255–281
  3. 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
  4. Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature. 1993;365:61–65
  5. 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
  6. Sugiura T, Kondo S, Sukagawa A, et al. 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Commun. 1995;15:89–97
  7. Mechoulam R, Benshabat 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
  8. Cota D, Woods SC. The role of the endocannabinoid system in the regulation of energy homeostasis. Curr Opin Endocrinol Diabetes. 2005;12:338–351
  9. 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
  10. Di Marzo V, Goparaju SK, Wang L, et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature. 2001;410:822–825
  11. Ravinet Trillou C, Arnone M, Delgorge C, et al. Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. Am J Physiol Regul Integr Comp Physiol. 2003;284:R345–R353
  12. 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
  13. Liu YL, Connoley IP, Wilson CA, Stock MJ. Effects of the cannabinoid CB1 receptor antagonist SR141716 on oxygen consumption and soleus muscle glucose uptake in Lepob/Lepob mice. Int J Obes (Lond). 2005;29:183–187
  14. Bensaid M, Gary-Bobo M, Esclangon A, Moffrand JP, LeFur G, Oury-Donat F, et al. The cannabinoid CB1 receptor antagonist SR141716 increases acrp20 mRNA expression in adipose tissue of obese fa/fa rats and in cultured adipocyte cells. Mol Pharmacol. 2003;63:908–914
  15. Jo YH, Chen YJ, Chua SC, Talmage DA, Role LW. Integration of endocannabinoid and leptin signaling in an appetite-related neural circuit. Neuron. 2005;48:1055–1066
  16. Poirier B, Bidouard J-P, 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
  17. Pocai A, Obici S, Schwartz GJ, Rossetti L. A brain-liver circuit regulates glucose homeostasis. Cell Metab. 2005;1:53–61
  18. Diraison F, Yankah V, Letexier D, Dusserre E, Jones P, Beylot M. Differences in the regulation of adipose tissue and liver lipogenesis by carbohydrates in humans. J Lipid Res. 2003;44:846–853
  19. Brown MS, Goldstein JL. Sterol regulatory element binding proteins (SREBPs): controllers of lipid synthesis and cellular uptake. Nutr Rev. 1998;56(pt 2):S1–S3
  20. 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
  21. Biddinger SB, Almind K, Miyazaki M, Kokkotou E, Ntambi JM, Kahn CR. Effects of diet and genetic background on sterol response element binding protein 1c and stearoyl CoA-desaturase-1 and the development of the metabolic syndrome. Diabetes. 2005;54:1314–1323
  22. Savage DB, Choi S, Samuel VT, et al. Reversal of diet-induced hepatic steatosis and hepatic insulin resistance by antisense oligonucleotide inhibitors of acetyl-CoA carboxylases 1 and 2. J Clin Invest. 2006;116:817–824
  23. Sampath H, Miyazaki M, Dobrzyn A, Ntambi JM. Stearoyl CoA-desaturase-1 mediates the pro-lipogenic effects of dietary saturated fat. J Biol Chem. 2007;282:2483–2493
  24. Lin J, Yang R, Tarr PT, et al. Hyperlipidemic effects of dietary saturated fats mediated through PGC-1β coactivation of SREBP. Cell. 2005;120:261–273

PII: S0002-9343(07)00547-5

doi: 10.1016/j.amjmed.2007.06.007

The American Journal of Medicine
Volume 120, Issue 9, Supplement 1 , Pages S18-S24 , September 2007

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