CB1 Signaling in Forebrain and Sympathetic Neurons Is a Key Determinant of Endocannabinoid Actions on Energy Balance

被引：166

作者：

Quarta, Carmelo ^{[1
,2
]}

Bellocchio, Luigi ^{[3
,4
]}

Mancini, Giacomo ^{[5
]}

Mazza, Roberta ^{[1
,2
]}

Cervino, Cristina ^{[1
,2
]}

Braulke, Luzie J. ^{[7
]}

Fekete, Csaba ^{[8
,9
,10
]}

Latorre, Rocco ^{[11
,12
]}

Nanni, Cristina ^{[13
]}

Bucci, Marco ^{[1
,2
,14
]}

Clemens, Laura E. ^{[7
]}

Heldmaier, Gerhard ^{[7
]}

Watanabe, Masahiko ^{[15
]}

Leste-Lassere, Thierry ^{[3
,4
]}

Maitre, Marlene ^{[3
,4
]}

Tedesco, Laura ^{[16
,17
]}

Fanelli, Flaminia ^{[1
,2
]}

Reuss, Stefan ^{[6
]}

Klaus, Susanne ^{[18
]}

Srivastava, Raj Kamal ^{[5
]}

Monory, Krisztina ^{[5
]}

Valerio, Alessandra ^{[16
,19
]}

Grandis, Annamaria ^{[20
]}

De Giorgio, Roberto ^{[11
,12
]}

Pasquali, Renato ^{[1
,2
]}

Nisoli, Enzo ^{[16
,17
]}

Cota, Daniela ^{[3
,4
]}

Lutz, Beat ^{[5
]}

Marsicano, Giovanni ^{[3
,4
]}

Pagotto, Uberto ^{[1
,2
]}

机构：

[1] Univ Bologna, Endocrinol Unit, I-40138 Bologna, Italy

[2] Univ Bologna, Dept Clin Med, Ctr Ric Biomed Applicata, I-40138 Bologna, Italy

[3] Neuroctr Magendie, INSERM, U862, F-33077 Bordeaux, France

[4] Univ Bordeaux, F-33077 Bordeaux, France

[5] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Physiol Chem, D-55099 Mainz, Germany

[6] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Anat & Cell Biol, D-55099 Mainz, Germany

[7] Univ Marburg, Dept Biol Anim Physiol, D-35032 Marburg, Germany

[8] Hungarian Acad Sci, Inst Expt Med, Dept Endocrine Neurobiol, H-1083 Budapest, Hungary

[9] Tufts Med Ctr, Tupper Res Inst, Div Endocrinol Diabet & Metab, Boston, MA 02111 USA

[10] Tufts Med Ctr, Dept Med, Boston, MA 02111 USA

[11] Univ Bologna, Dept Clin Med, S Orsola Malpighi Hosp, I-40138 Bologna, Italy

[12] Univ Bologna, Ctr Ric Biomed Applicata, S Orsola Malpighi Hosp, I-40138 Bologna, Italy

[13] Univ Bologna, Dept Nucl Med, S Orsola Malpighi Hosp, I-40138 Bologna, Italy

[14] Univ Turku, Turku PET Ctr, Turku 20521, Finland

[15] Hokkaido Univ, Sch Med, Dept Anat, Sapporo, Hokkaido 0608638, Japan

[16] Univ Milan, Integrated Labs Network, Ctr Study & Res Obes, Dept Pharmacol Chemotherapy & Med Toxicol, I-20129 Milan, Italy

[17] Ist Auxol Italian, I-20145 Milan, Italy

[18] German Inst Human Nutr Potsdam Rehbrucke, Dept Pharmacol, D-14558 Nuthetal, Germany

[19] Univ Brescia, Dept Biomed Sci & Biotechnol, I-25123 Brescia, Italy

[20] Univ Bologna, Dept Vet Morphophysiol & Anim Prod, I-40138 Bologna, Italy

来源：

CELL METABOLISM | 2010年 / 11卷 / 04期

关键词：

DIET-INDUCED OBESITY; CANNABINOID RECEPTOR; FOOD-INTAKE; NITRIC-OXIDE; SYSTEM; RIMONABANT; SUPPRESSION; EXPENDITURE; ANTAGONISM; EXPRESSION;

D O I：

10.1016/j.cmet.2010.02.015

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The endocannabinoid system (ECS) plays a critical role in obesity development. The pharmacological blockade of cannabinoid receptor type 1 (CB1) has been shown to reduce body weight and to alleviate obesity-related metabolic disorders. An unsolved question is at which anatomical level CB1 modulates energy balance and the mechanisms involved in its action. Here, we demonstrate that CB1 receptors expressed in forebrain and sympathetic neurons play a key role in the pathophysiological development of diet-induced obesity. Conditional mutant mice lacking CB1 expression in neurons known to control energy balance, but not in nonneuronal peripheral organs, displayed a lean phenotype and resistance to diet-induced obesity. This phenotype results from an increase in lipid oxidation and thermogenesis as a consequence of an enhanced sympathetic tone and a decrease in energy absorption. In conclusion, CB1 signaling in the forebrain and sympathetic neurons is a key determinant of the ECS control of energy balance.

引用

页码：273 / 285

页数：13

共 32 条

[1] The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake [J].

Addy, Carol ;

Wright, Hamish ;

Van Laere, Koen ;

Gantz, Ira ;

Erondu, Ngozi ;

Musser, Bret J. ;

Lu, Kaifeng ;

Yuan, Jinyu ;

Sanabria-Bohorquez, Sandra M. ;

Stoch, Aubrey ;

Stevens, Cathy ;

Fong, Tung M. ;

De Lepeleire, Inge ;

Cilissen, Caroline ;

Cote, Josee ;

Rosko, Kim ;

Gendrano, Isaias N., III ;

Nguyen, Allison Martin ;

Gumbiner, Barry ;

Rothenberg, Paul ;

de Hoon, Jan ;

Bormans, Guy ;

Depre, Marleen ;

Eng, Wai-Si ;

Ravussin, Eric ;

Klein, Samuel ;

Blundell, John ;

Herman, Gary A. ;

Burns, H. Donald ;

Hargreaves, Richard J. ;

Wagner, John ;

Gottesdiener, Keith ;

Amatruda, John M. ;

Heymsfield, Steven B. .

CELL METABOLISM, 2008, 7 (01) :68-78

[2] A critical review of the cannabinoid receptor as a drug target for obesity management [J].

Akbas, F. ;

Gasteyger, C. ;

Sjodin, A. ;

Astrup, A. ;

Larsen, T. M. .

OBESITY REVIEWS, 2009, 10 (01) :58-67

[3] A CamKIIα iCre BAC allows brain-specific gene inactivation [J].

Casanova, E ;

Fehsenfeld, S ;

Mantamadiotis, T ;

Lemberger, T ;

Greiner, E ;

Stewart, AF ;

Schütz, G .

GENESIS, 2001, 31 (01) :37-42

[4]

Cota D, 2003, J CLIN INVEST, V112, P423, DOI 10.1172/JCI17725

[5] Food Intake-independent Effects of CB1 Antagonism on Glucose and Lipid Metabolism [J].

Cota, Daniela ;

Sandoval, Darleen A. ;

Olivieri, Massimiliano ;

Prodi, Elena ;

D'Alessio, David A. ;

Woods, Stephen C. ;

Seeley, Randy J. ;

Obici, Silvana .

OBESITY, 2009, 17 (08) :1641-1645

[6] Leptin-regulated endocannabinoids are involved in maintaining food intake [J].

Di Marzo, V ;

Goparaju, SK ;

Wang, L ;

Liu, J ;

Bátkai, S ;

Járai, Z ;

Fezza, F ;

Miura, GI ;

Palmiter, RD ;

Sugiura, T ;

Kunos, G .

NATURE, 2001, 410 (6830) :822-825

[7] Two distinct classes of muscarinic action on hippocampal inhibitory synapses:: M2-mediated direct suppression and M1/M3-mediated indirect suppression through endocannabinoid signalling [J].

Fukudome, Y ;

Ohno-Shosaku, T ;

Matsui, M ;

Omori, Y ;

Fukaya, M ;

Tsubokawa, H ;

Taketo, MM ;

Watanabe, M ;

Manabe, T ;

Kano, M .

EUROPEAN JOURNAL OF NEUROSCIENCE, 2004, 19 (10) :2682-2692

[8] Epithelial and mesenchymal tumor compartments exhibit in vivo complementary patterns of vascular perfusion and glucose metabolism [J].

Galie, Mirco ;

Farace, Paolo ;

Nanniy, Cristina ;

Spinelli, Antonello ;

Nicolato, Elena ;

Boschi, Federico ;

Magnani, Paolo ;

Trespidi, Silvia ;

Ambrosiniy, Valentina ;

Fantiy, Stefano ;

Merigo, Flavia ;

Osculati, Francesco ;

Marzola, Pasquina ;

Sbarbati, Andrea .

NEOPLASIA, 2007, 9 (11) :900-908

[9] The nucleus tractus solitarius: a portal for visceral afferent signal processing, energy status assessment and integration of their combined effects on food intake [J].

Grill, H. J. ;

Hayes, M. R. .

INTERNATIONAL JOURNAL OF OBESITY, 2009, 33 :S11-S15

[10] IMPROVEMENTS IN AUTOMATED-ANALYSIS OF CATECHOLAMINE AND RELATED METABOLITES IN BIOLOGICAL SAMPLES BY COLUMN-SWITCHING HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY [J].

GROSSI, G ;

BARGOSSI, AM ;

LUCARELLI, C ;

PARADISI, R ;

SPROVIERI, C ;

SPROVIERI, G .

JOURNAL OF CHROMATOGRAPHY, 1991, 541 (1-2) :273-284

← 1 2 3 4 →