{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T14:18:03Z","timestamp":1791728283751,"version":"4.3.4"},"reference-count":37,"publisher":"The Endocrine Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Context: Cannabinoid CB1 receptor blockade decreases weight and hyperinsulinemia in obese animals and humans in a way greatly independent from food intake.<\/jats:p>\n                  <jats:p>Objective: The objective of this study was to investigate the regulation and function of the endocannabinoid system in adipocytes and pancreatic \u03b2-cells.<\/jats:p>\n                  <jats:p>Design, Setting, and Patients: Mouse 3T3-F442A adipocytes and rat insulinoma RIN-m5F \u03b2-cells, pancreas and fat from mice with diet-induced obesity, visceral and sc fat from patients with body mass index equal to or greater than 30 kg\/m2, and serum from normoglycemic and type 2 diabetes patients were studied.<\/jats:p>\n                  <jats:p>Main Outcome Measure: Endocannabinoid enzyme and adipocyte protein expression, and endocannabinoid and insulin levels were measured.<\/jats:p>\n                  <jats:p>Results: Endocannabinoids are present in adipocytes with levels peaking before differentiation, and in RIN-m5F \u03b2-cells, where they are under the negative control of insulin. Chronic treatment of adipocytes with insulin is accompanied by permanently elevated endocannabinoid signaling, whereas culturing of RIN-m5F \u03b2-cells in high glucose transforms insulin down-regulation of endocannabinoid levels into up-regulation. Epididymal fat and pancreas from mice with diet-induced obesity contain higher endocannabinoid levels than lean mice. Patients with obesity or hyperglycemia caused by type 2 diabetes exhibit higher concentrations of endocannabinoids in visceral fat or serum, respectively, than the corresponding controls. CB1 receptor stimulation increases lipid droplets and decreases adiponectin expression in adipocytes, and it increases intracellular calcium and insulin release in RIN-m5F \u03b2-cells kept in high glucose.<\/jats:p>\n                  <jats:p>Conclusions: Peripheral endocannabinoid overactivity might explain why CB1 blockers cause weight-loss independent reduction of lipogenesis, of hypoadiponectinemia, and of hyperinsulinemia in obese animals and humans.<\/jats:p>","DOI":"10.1210\/jc.2005-2679","type":"journal-article","created":{"date-parts":[[2006,5,9]],"date-time":"2006-05-09T23:35:54Z","timestamp":1147217754000},"page":"3171-3180","source":"Crossref","is-referenced-by-count":577,"title":["Regulation, Function, and Dysregulation of Endocannabinoids in Models of Adipose and \u03b2-Pancreatic Cells and in Obesity and Hyperglycemia"],"prefix":"10.1210","volume":"91","author":[{"given":"Isabel","family":"Matias","sequence":"first","affiliation":[{"name":"Endocannabinoid Research Group (I.M., P.O., L.D.P., S.P., V.D.M.) 40138 Bologna, Italy"},{"name":"Institutes of Biomolecular Chemistry (I.M., S.P., V.D.M.), 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Paule","family":"Gonthier","sequence":"additional","affiliation":[{"name":"Universite\u0301 de La Re\u0301union (M.-P.G., L.H., F.F., R.R.), 97715 La Re\u0301union, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierangelo","family":"Orlando","sequence":"additional","affiliation":[{"name":"Endocannabinoid Research Group (I.M., P.O., L.D.P., S.P., V.D.M.) 40138 Bologna, Italy"},{"name":"Biochemistry of Proteins (P.O.), 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilis","family":"Martiadis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry (V.M., M.M., P.M.), Second University of Naples, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"De Petrocellis","sequence":"additional","affiliation":[{"name":"Endocannabinoid Research Group (I.M., P.O., L.D.P., S.P., V.D.M.) 40138 Bologna, Italy"},{"name":"Cybernetics (L.D.P.), National Research Council, 80078 Pozzuoli (NA), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Cervino","sequence":"additional","affiliation":[{"name":"Endocrinology Unit (C.C., R.P., U.P.), Department of Internal Medicine and Gastroenterology, Center of Applied Biomedical Research, S. Orsola-Malpighi General Hospital, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Petrosino","sequence":"additional","affiliation":[{"name":"Endocannabinoid Research Group (I.M., P.O., L.D.P., S.P., V.D.M.) 40138 Bologna, Italy"},{"name":"Institutes of Biomolecular Chemistry (I.M., S.P., V.D.M.), 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Hoareau","sequence":"additional","affiliation":[{"name":"Universite\u0301 de La Re\u0301union (M.-P.G., L.H., F.F., R.R.), 97715 La Re\u0301union, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Festy","sequence":"additional","affiliation":[{"name":"Universite\u0301 de La Re\u0301union (M.-P.G., L.H., F.F., R.R.), 97715 La Re\u0301union, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Pasquali","sequence":"additional","affiliation":[{"name":"Endocrinology Unit (C.C., R.P., U.P.), Department of Internal Medicine and Gastroenterology, Center of Applied Biomedical Research, S. Orsola-Malpighi General Hospital, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regis","family":"Roche","sequence":"additional","affiliation":[{"name":"Universite\u0301 de La Re\u0301union (M.-P.G., L.H., F.F., R.R.), 97715 La Re\u0301union, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Maj","sequence":"additional","affiliation":[{"name":"Department of Psychiatry (V.M., M.M., P.M.), Second University of Naples, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uberto","family":"Pagotto","sequence":"additional","affiliation":[{"name":"Endocrinology Unit (C.C., R.P., U.P.), Department of Internal Medicine and Gastroenterology, Center of Applied Biomedical Research, S. Orsola-Malpighi General Hospital, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palmiero","family":"Monteleone","sequence":"additional","affiliation":[{"name":"Department of Psychiatry (V.M., M.M., P.M.), Second University of Naples, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Di Marzo","sequence":"additional","affiliation":[{"name":"Endocannabinoid Research Group (I.M., P.O., L.D.P., S.P., V.D.M.) 40138 Bologna, Italy"},{"name":"Institutes of Biomolecular Chemistry (I.M., S.P., V.D.M.), 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613593322100_R1","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/nrd1495","article-title":"The endocannabinoid system and its therapeutic exploitation","volume":"3","author":"Di Marzo","year":"2004","journal-title":"Nat Rev Drug Discov"},{"key":"2020071613593322100_R2","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nn1457","article-title":"Endocannabinoid control of food intake and energy balance","volume":"8","author":"Di Marzo","year":"2005","journal-title":"Nat Neurosci"},{"key":"2020071613593322100_R3","doi-asserted-by":"crossref","first-page":"215","DOI":"10.2174\/1389450053174514","article-title":"Cannabinoids and the regulation of ingestive behaviour","volume":"6","author":"Vickers","year":"2005","journal-title":"Curr Drug Targets"},{"key":"2020071613593322100_R4","doi-asserted-by":"crossref","first-page":"PL113","DOI":"10.1016\/S0024-3205(98)00322-1","article-title":"Appetite suppression and weight loss after the cannabinoid antagonist SR 141716","volume":"63","author":"Colombo","year":"1998","journal-title":"Life Sci"},{"key":"2020071613593322100_R5","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s00213-002-1384-8","article-title":"Preferential effects of the cannabinoid CB1 receptor antagonist, SR 141716, on food intake and body weight gain of obese (fa\/fa) compared to lean Zucker rats","volume":"167","author":"Vickers","year":"2003","journal-title":"Psychopharmacology (Berl)"},{"key":"2020071613593322100_R6","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/S0031-9384(04)00302-6","article-title":"Cannabinoid (CB)1 receptor antagonist, AM 251, causes a sustained reduction of daily food intake in the rat","volume":"82","author":"Chambers","year":"2004","journal-title":"Physiol Behav"},{"key":"2020071613593322100_R7","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/35071088","article-title":"Leptin-regulated endocannabinoids are involved in maintaining food intake","volume":"410","author":"Di Marzo","year":"2001","journal-title":"Nature"},{"key":"2020071613593322100_R8","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/sj.bjp.0704767","article-title":"Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: stimulation of eating by 2-arachidonoyl glycerol","volume":"136","author":"Kirkham","year":"2002","journal-title":"Br J Pharmacol"},{"key":"2020071613593322100_R9","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s002130050953","article-title":"Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors","volume":"143","author":"Williams","year":"1999","journal-title":"Psychopharmacology (Berl)"},{"key":"2020071613593322100_R10","doi-asserted-by":"crossref","first-page":"R345","DOI":"10.1152\/ajpregu.00545.2002","article-title":"Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice","volume":"284","author":"Ravinet Trillou","year":"2003","journal-title":"Am J Physiol Regu Integr Comp Physiol"},{"key":"2020071613593322100_R11","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1463-1326.2004.00374.x","article-title":"The anti-obesity effect of rimonabant is associated with an improved serum lipid profile","volume":"7","author":"Poirier","year":"2005","journal-title":"Diabetes Obes Metab"},{"key":"2020071613593322100_R12","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/sj.ijo.0802583","article-title":"CB1 cannabinoid receptor knockout in mice leads to leanness, resistance to diet-induced obesity and enhanced leptin sensitivity","volume":"28","author":"Ravinet Trillou","year":"2004","journal-title":"Int J Obes Relat Metab Disord"},{"key":"2020071613593322100_R13","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1172\/JCI17725","article-title":"The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis","volume":"112","author":"Cota","year":"2003","journal-title":"J Clin Invest"},{"key":"2020071613593322100_R14","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1172\/JCI200523057","article-title":"Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity","volume":"115","author":"Osei-Hyiaman","year":"2005","journal-title":"J Clin Invest"},{"key":"2020071613593322100_R15","article-title":"Detection, evaluation and treatment of high blood cholesterol in adults","author":"National Cholesterol Education Program","year":"2001"},{"key":"2020071613593322100_R16","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1016\/S0140-6736(05)66374-X","article-title":"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","volume":"365","author":"Van Gaal","year":"2005","journal-title":"Lancet"},{"key":"2020071613593322100_R17","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1124\/mol.63.4.908","article-title":"The cannabinoid CB1 receptor antagonist SR141716 increases Acrp30 mRNA expression in adipose tissue of obese fa\/fa rats and in cultured adipocyte cells","volume":"63","author":"Bensaid","year":"2003","journal-title":"Mol Pharmacol"},{"key":"2020071613593322100_R18","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1055\/s-2004-830555","article-title":"Adipocytokines: fat-derived humoral mediators of metabolic homeostasis","volume":"113","author":"Staiger","year":"2005","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"2020071613593322100_R19","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.ceca.2005.10.005","article-title":"Cannabinoid receptors regulate Ca2+ signals and insulin secretion in pancreatic \u03b2-cell","volume":"39","author":"Juan-Pico","year":"2006","journal-title":"Cell Calcium"},{"key":"2020071613593322100_R20","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/BF00316069","article-title":"Quantitation of adipose conversion and triglycerides by staining intra-cyctoplasmic lipids with Oil Red O","volume":"97","author":"Ramirez","year":"1992","journal-title":"Histochemistry"},{"key":"2020071613593322100_R21","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1007\/BF01953269","article-title":"The induction of diabetes in rats by intramuscular administration of streptozotocin","volume":"35","author":"Nakhoda","year":"1979","journal-title":"Experientia"},{"key":"2020071613593322100_R22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1476-511X-2-5","article-title":"Endocannabinoid signalling in the blood of patients with schizophrenia","volume":"2","author":"De Marchi","year":"2003","journal-title":"Lipids Health Dis"},{"key":"2020071613593322100_R23","doi-asserted-by":"crossref","first-page":"32726","DOI":"10.1074\/jbc.M302123200","article-title":"Progesterone activates fatty acid amide hydrolase (FAAH) promoter in human T lymphocytes through the transcription factor Ikaros. Evidence for a synergistic effect of leptin","volume":"278","author":"Maccarrone","year":"2003","journal-title":"J Biol Chem"},{"key":"2020071613593322100_R24","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/molehr\/gah130","article-title":"Up-regulation of the endocannabinoid system in the uterus of leptin knockout (ob\/ob) mice and implications for fertility","volume":"11","author":"Maccarrone","year":"2005","journal-title":"Mol Hum Reprod"},{"key":"2020071613593322100_R25","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.mce.2004.04.017","article-title":"Cell lines derived from pancreatic islets","volume":"228","author":"Hohmeier","year":"2004","journal-title":"Mol Cell Endocrinol"},{"key":"2020071613593322100_R26","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1210\/jc.2004-1711","article-title":"Adiponectinemia in visceral obesity: impact on glucose tolerance and plasma lipoprotein and lipid levels in men","volume":"90","author":"Cote","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613593322100_R27","article-title":"One-year treatment with rimonabant increases plasma adiponectin levels beyond weight loss:","author":"Despre\u0301s","year":"2005"},{"key":"2020071613593322100_R28","article-title":"The potential of rimonabant in prediabetes: pooled 1-year results from RIO-Lipids, RIO-Europe and RIO-North America studies.","author":"Rosenstok","year":"2005"},{"key":"2020071613593322100_R29","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1056\/NEJMoa044537","article-title":"Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia","volume":"353","author":"Despre\u0301s","year":"2005","journal-title":"N Engl J Med"},{"key":"2020071613593322100_R30","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1124\/mol.105.015040","article-title":"The cannabinoid CB1 receptor antagonist rimonabant (SR141716) inhibits cell proliferation and increases markers of adipocyte maturation in cultured mouse 3T3 F442A preadipocytes","volume":"69","author":"Gary-Bobo","year":"2006","journal-title":"Mol Pharmacol"},{"key":"2020071613593322100_R31","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1096\/fj.04-3177fje","article-title":"The CB1 receptor antagonist rimonabant reverses the diet-induced obesity phenotype through the regulation of lipolysis and energy balance","volume":"19","author":"Jbilo","year":"2005","journal-title":"FASEB J"},{"key":"2020071613593322100_R32","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1007\/s00018-003-3453-5","article-title":"Differential diurnal variations of anandamide and 2-arachidonoyl-glycerol levels in rat brain","volume":"61","author":"Valenti","year":"2004","journal-title":"Cell Mol Life Sci"},{"key":"2020071613593322100_R33","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/(SICI)1098-2396(19990901)33:3<181::AID-SYN3>3.0.CO;2-R","article-title":"Analysis of cannabinoid receptor binding and mRNA expression and endogenous cannabinoid contents in the developing rat brain during late gestation and early postnatal period","volume":"33","author":"Berrendero","year":"1999","journal-title":"Synapse"},{"key":"2020071613593322100_R34","doi-asserted-by":"crossref","first-page":"33896","DOI":"10.1074\/jbc.M303994200","article-title":"The endocannabinoid system in human keratinocytes. Evidence that anandamide inhibits epidermal differentiation through CB1 receptor-dependent inhibition of protein kinase C, activation protein-1, and transglutaminase","volume":"278","author":"Maccarrone","year":"2003","journal-title":"J Biol Chem"},{"key":"2020071613593322100_R35","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/sj.ijo.0802954","article-title":"Overweight and obesity associated with a missense polymorphism in fatty acid amide hydrolase (FAAH)","volume":"29","author":"Sipe","year":"2005","journal-title":"Int J Obes Relat Metab Disord"},{"key":"2020071613593322100_R36","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1038\/sj.npp.1300695","article-title":"Blood levels of the endocannabinoid anandamide are increased in anorexia nervosa and in binge-eating disorder, but not in bulimia nervosa","volume":"30","author":"Monteleone","year":"2005","journal-title":"Neuropsychopharmacology"},{"key":"2020071613593322100_R37","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.2337\/diabetes.54.10.2838","article-title":"Activation of the peripheral endocannabinoid system in human obesity","volume":"54","author":"Engeli","year":"2005","journal-title":"Diabetes"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/91\/8\/3171\/10443247\/jcem3171.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/91\/8\/3171\/10443247\/jcem3171.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T21:08:12Z","timestamp":1594933692000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/91\/8\/3171\/2656716"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,8,1]]},"references-count":37,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2006,8,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2005-2679","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,8,1]]}}}