Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Published online February 14, 2008
Diabetes 57:1262-1268, 2008
DOI: 10.2337/db07-1186
© 2008 by the American Diabetes Association
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
db07-1186v1
57/5/1262    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Google Scholar
Right arrow Articles by D'Eon, T. M.
Right arrow Articles by Teixeira, S. R.
PubMed
Right arrow PubMed Citation
Right arrow Articles by D'Eon, T. M.
Right arrow Articles by Teixeira, S. R.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

The Role of Adipocyte Insulin Resistance in the Pathogenesis of Obesity-Related Elevations in Endocannabinoids

Tara M. D'Eon, Kerry A. Pierce, Jeffery J. Roix, Andrew Tyler, Hong Chen, and Sandra R. Teixeira

From the Diabetes and Metabolism Disease Area, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts

Corresponding author: Tara D'Eon, PhD, Metabolism Medical Team, sanofi-aventis, One Onslow Street, Guildford, Surrey, U.K., GU1 4YS. E-mail: tara.d'eon{at}sanofi-aventis.com

Abbreviations: 2-AG, 2-arachidonylglycerol; AEA, anandamide; CB1R, cannabinoid 1 receptor; DAGL, diacylglycerol lipase; EC, endocannabinoid; FAAH, fatty acid amide hydrolase; FBS, fetal bovine serum; MAGL, monoacylglycerol lipase; NAPE-PLD, N-arachidonoylphosphotitylethanolamine phospholipase D

OBJECTIVE— Obesity is associated with an overactive endocannabinoid (EC) system. The mechanisms responsible for increased ECs in obese individuals are poorly understood. Therefore, we examined the role of adipocyte insulin resistance in intracellular EC metabolism.

METHODS— We used 3T3-L1 adipocytes and diet-induced obese (DIO) mice to examine the role of obesity and insulin resistance in the regulation and/or dysregulation of intracellular ECs.

RESULTS— For the first time, we provide evidence that insulin is a major regulator of EC metabolism. Insulin treatment reduced intracellular ECs (2-arachidonylglycerol [2-AG] and anandamide [AEA]) in 3T3-L1 adipocytes. This corresponded with insulin-sensitive expression changes in enzymes of EC metabolism. In insulin-resistant adipocytes, patterns of insulin-induced enzyme expression were disturbed in a manner consistent with elevated EC synthesis and reduced EC degradation. Expression profiling of adipocytes from DIO mice largely recapitulated in vitro changes, suggesting that insulin resistance affects the EC system in vivo. In mice, expression changes of EC synthesis and degradation enzymes were accompanied by increased plasma EC concentrations (2-AG and AEA) and elevated adipose tissue 2-AG.

CONCLUSIONS— Our findings suggest that insulin-resistant adipocytes fail to regulate EC metabolism and decrease intracellular EC levels in response to insulin stimulation. These novel observations offer a mechanism whereby obese insulin-resistant individuals exhibit increased concentrations of ECs.


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




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2008 by the American Diabetes Association.