| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
-HSD1 inhibition improves triglyceridemia through reduced liver VLDL secretion and partitions lipids towards oxidative tissues
1 Laval Hospital Research Center, Laval University, Quebec, Canada
2 Anatomy and Physiology, Laval University; Laval Hospital Research Center, Quebec, Canada
3 Anatomy & Physiology, Laval University, Ste Foy, Canada
4 Kinesiology, University of Southern California, Los Angeles, California, United States
5 Departement de Medicine Sociale et Preventive, Universite Laval, Quebec, Canada
6 Umea University, Umea, Sweden
7 External Scientific Affairs, Merck Research Laboratories, Rahway, New Jersey, United States
* To whom correspondence should be addressed. E-mail: yves.deshaies{at}phs.ulaval.ca.
Tissue-specific alterations in 11
-HSD1 activity, which amplifies glucocorticoid action, are thought to contribute to some of the metabolic complications of obesity. The present study tested whether hypertriglyceridemia is one such complication by investigating the effects of an 11-HSD1 inhibitor (Compound A, 3 mg/kg/d, 21 days) on triglyceride (TG) metabolism in a rat model of diet-induced obesity. The dose of Compound A used did not affect food intake or final body weight. Compound A improved fasting triglyceridemia (-42%) through a robust reduction (-41%) in hepatic TG secretion rate, without change in plasma TG clearance rate. Uptake of TG-derived fatty acids was, however, increased in oxidative tissues including red gastrocnemius (+47%), heart (+39%), and brown adipose tissue (BAT, +46%) at the expense of the liver, with a concomitant increase in the fatty acid binding protein FABPpm. Lipid oxidation products were increased in red gastrocnemius (+35%) and heart (+33%), as were levels of UCP1 mRNA in BAT (+48%), and CPT1 activity tended to be increased in some oxidative tissues. These findings demonstrate that pharmacological inhibition of 11-HSD1 at a dose that does not affect food intake improves triglyceridemia by reducing hepatic VLDL-TG secretion, with a shift in the pattern of TG-derived fatty acid uptake towards oxidative tissues, in which lipid accumulation is prevented by increased lipid oxidation.
This article has been cited by other articles:
|
|
 |
|
  S. A. Morgan, M. Sherlock, L. L. Gathercole, G. G. Lavery, C. Lenaghan, I. J. Bujalska, D. Laber, A. Yu, G. Convey, R. Mayers, et al. 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Regulates Glucocorticoid-Induced Insulin Resistance in Skeletal Muscle Diabetes, November 1, 2009; 58(11): 2506 - 2515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. P Macfarlane, S. Forbes, and B. R Walker Glucocorticoids and fatty acid metabolism in humans: fuelling fat redistribution in the metabolic syndrome J. Endocrinol., May 1, 2008; 197(2): 189 - 204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Nuotio-Antar, D. L. Hachey, and A. H. Hasty Carbenoxolone treatment attenuates symptoms of metabolic syndrome and atherogenesis in obese, hyperlipidemic mice Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1517 - E1528. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
