HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Online-Only Appendix All Versions of this Article: db08-0161v1 57/11/2977    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Nogueiras, R. Articles by Tschöp, M. H. PubMed PubMed Citation Articles by Nogueiras, R. Articles by Tschöp, M. H. Social Bookmarking                What's this?

Peripheral, but Not Central, CB1 Antagonism Provides Food Intake–Independent Metabolic Benefits in Diet-Induced Obese Rats

¹ Department of Psychiatry, Obesity Research Centre, Genome Research Institute, University of Cincinnati, Cincinnati, Ohio
² Department of Physiology, School of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain
³ CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
⁴ Laboratory of Metabolism, Division of Endocrinology, Diabetology, and Nutrition, Department of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland
⁵ Procter and Gamble Pharmaceuticals, Mason, Ohio
⁶ Laboratory of Trauma, Sepsis and Inflammation Research, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio
⁷ Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
⁸ Department of Anatomy, Hokkaido University School of Medicine, Sapporo, Japan
⁹ Tupper Research Institute and Department of Medicine, Division of Endocrinology, Diabetes, Metabolism, and Molecular Medicine, New England Medical Center, Boston, Massachusetts
¹⁰ Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio

Corresponding authors: Ruben Nogueiras, ruben.nogueiras{at}usc.es, and Matthias H. Tschöp, tschoemh{at}ucmail.uc.edu

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.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?