Peripheral, but Not Central, CB1 antagonism provides food intake-independent metabolic benefits in diet-induced obese rats

Ruben Nogueiras, Christelle Veyrat-Durebex, Paula M. Suchanek, Marcella Klein, Johannes Tschöp, Charles Caldwell, Stephen C. Woods, Gabor Wittmann, Masahiko Watanabe, Z. Liposits, Csaba Fekete, Ofer Reizes, Francoise Rohner-Jeanrenaud, Matthias H. Tschöp

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

OBJECTIVE-Blockade of the CB1 receptor is one of the promising strategies for the treatment of obesity. Although antagonists suppress food intake and reduce body weight, the role of central versus peripheral CB1 activation on weight loss and related metabolic parameters remains to be elucidated. We therefore specifically assessed and compared the respective potential relevance of central nervous system (CNS) versus peripheral CB1 receptors in the regulation of energy homeostasis and lipid and glucose metabolism in diet-induced obese (DIO) rats. RESEARCH DESIGN AND METHODS-Both lean and DIO rats were used for our experiments. The expression of key enzymes involved in lipid metabolism was measured by real-time PCR, and euglycemic-hyperinsulinemic clamps were used for insulin sensitivity and glucose metabolism studies. RESULTS-Specific CNS-CB1 blockade decreased body weight and food intake but, independent of those effects, had no beneficial influence on peripheral lipid and glucose metabolism. Peripheral treatment with CB1 antagonist (Rimonabant) also reduced food intake and body weight but, in addition, independently triggered lipid mobilization pathways in white adipose tissue and cellular glucose uptake. Insulin sensitivity and skeletal muscle glucose uptake were enhanced, while hepatic glucose production was decreased during peripheral infusion of the CB1 antagonist. However, these effects depended on the antagonist- elicited reduction of food intake. CONCLUSIONS-Several relevant metabolic processes appear to independently benefit from peripheral blockade of CB1, while CNS-CB1 blockade alone predominantly affects food intake and body weight.

Original languageEnglish
Pages (from-to)2977-2991
Number of pages15
JournalDiabetes
Volume57
Issue number11
DOIs
Publication statusPublished - Nov 2008

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Eating
Diet
Glucose
Lipid Metabolism
Body Weight
Cannabinoid Receptor CB1
rimonabant
Central Nervous System
Insulin Resistance
Lipid Mobilization
White Adipose Tissue
Glucose Clamp Technique
Weight Loss
Real-Time Polymerase Chain Reaction
Skeletal Muscle
Homeostasis
Research Design
Obesity
Liver
Enzymes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Nogueiras, R., Veyrat-Durebex, C., Suchanek, P. M., Klein, M., Tschöp, J., Caldwell, C., ... Tschöp, M. H. (2008). Peripheral, but Not Central, CB1 antagonism provides food intake-independent metabolic benefits in diet-induced obese rats. Diabetes, 57(11), 2977-2991. https://doi.org/10.2337/db08-0161

Peripheral, but Not Central, CB1 antagonism provides food intake-independent metabolic benefits in diet-induced obese rats. / Nogueiras, Ruben; Veyrat-Durebex, Christelle; Suchanek, Paula M.; Klein, Marcella; Tschöp, Johannes; Caldwell, Charles; Woods, Stephen C.; Wittmann, Gabor; Watanabe, Masahiko; Liposits, Z.; Fekete, Csaba; Reizes, Ofer; Rohner-Jeanrenaud, Francoise; Tschöp, Matthias H.

In: Diabetes, Vol. 57, No. 11, 11.2008, p. 2977-2991.

Research output: Contribution to journalArticle

Nogueiras, R, Veyrat-Durebex, C, Suchanek, PM, Klein, M, Tschöp, J, Caldwell, C, Woods, SC, Wittmann, G, Watanabe, M, Liposits, Z, Fekete, C, Reizes, O, Rohner-Jeanrenaud, F & Tschöp, MH 2008, 'Peripheral, but Not Central, CB1 antagonism provides food intake-independent metabolic benefits in diet-induced obese rats', Diabetes, vol. 57, no. 11, pp. 2977-2991. https://doi.org/10.2337/db08-0161
Nogueiras R, Veyrat-Durebex C, Suchanek PM, Klein M, Tschöp J, Caldwell C et al. Peripheral, but Not Central, CB1 antagonism provides food intake-independent metabolic benefits in diet-induced obese rats. Diabetes. 2008 Nov;57(11):2977-2991. https://doi.org/10.2337/db08-0161
Nogueiras, Ruben ; Veyrat-Durebex, Christelle ; Suchanek, Paula M. ; Klein, Marcella ; Tschöp, Johannes ; Caldwell, Charles ; Woods, Stephen C. ; Wittmann, Gabor ; Watanabe, Masahiko ; Liposits, Z. ; Fekete, Csaba ; Reizes, Ofer ; Rohner-Jeanrenaud, Francoise ; Tschöp, Matthias H. / Peripheral, but Not Central, CB1 antagonism provides food intake-independent metabolic benefits in diet-induced obese rats. In: Diabetes. 2008 ; Vol. 57, No. 11. pp. 2977-2991.
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