The Emerging Role of the Endocannabinoid System in Endocrine Regulation and Energy Balance
Uberto Pagotto,
Giovanni Marsicano,
Daniela Cota,
Beat Lutz and
Renato Pasquali
Endocrinology Unit, Department of Internal Medicine and Gastroenterology, and Center for Applied Biomedical Research (U.P., R.P.), Sant’ Orsola-Malpighi Hospital, 40138 Bologna, Italy; Department of Physiological Chemistry (G.M., B.L.), Johannes Gutenberg-University Mainz, 55099 Mainz, Germany; and University of Cincinnati, Department of Psychiatry, Obesity Research Center, Genome Research Institute (D.C.), Cincinnati, Ohio 45237
Correspondence: Address all correspondence and requests for reprints to: Uberto Pagotto, M.D., Ph.D., Endocrinology Unit and Center for Applied Biomedical Research, Department of Internal Medicine and Gastroenterology, Sant’ Orsola-Malpighi Hospital, Via Massarenti, 9, 40138 Bologna, Italy. E-mail: pagube{at}med.unibo.it
During the last few years, the endocannabinoid system has emergedas a highly relevant topic in the scientific community. Manydifferent regulatory actions have been attributed to endocannabinoids,and their involvement in several pathophysiological conditionsis under intense scrutiny. Cannabinoid receptors, named CB1receptor and CB2 receptor, first discovered as the moleculartargets of the psychotropic component of the plant Cannabissativa, participate in the physiological modulation of manycentral and peripheral functions. CB2 receptor is mainly expressedin immune cells, whereas CB1 receptor is the most abundant Gprotein-coupled receptor expressed in the brain. CB1 receptoris expressed in the hypothalamus and the pituitary gland, andits activation is known to modulate all the endocrine hypothalamic-peripheralendocrine axes. An increasing amount of data highlights therole of the system in the stress response by influencing thehypothalamic-pituitary-adrenal axis and in the control of reproductionby modifying gonadotropin release, fertility, and sexual behavior.
The ability of the endocannabinoid system to control appetite,food intake, and energy balance has recently received greatattention, particularly in the light of the different modesof action underlying these functions. The endocannabinoid systemmodulates rewarding properties of food by acting at specificmesolimbic areas in the brain. In the hypothalamus, CB1 receptorand endocannabinoids are integrated components of the networkscontrolling appetite and food intake. Interestingly, the endocannabinoidsystem was recently shown to control metabolic functions byacting on peripheral tissues, such as adipocytes, hepatocytes,the gastrointestinal tract, and, possibly, skeletal muscle.The relevance of the system is further strenghtened by the notionthat drugs interfering with the activity of the endocannabinoidsystem are considered as promising candidates for the treatmentof various diseases, including obesity.
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