J. Lipid Res. Did you know there is a large type edition? Click here.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1194/jlr.M300240-JLR200 on October 1, 2003

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
M300240-JLR200v1
45/1/9    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
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 reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Muurling, M.
Right arrow Articles by Voshol, P. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Muurling, M.
Right arrow Articles by Voshol, P. J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Journal of Lipid Research, Vol. 45, 9-16, January 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Overexpression of APOC1 in obob mice leads to hepatic steatosis and severe hepatic insulin resistance

Martin Muurling*,{dagger}, Anita M. van den Hoek*,§, Ronald P. Mensink{dagger}, Hanno Pijl§, Johannes A. Romijn**, Louis M. Havekes*,§ and Peter J. Voshol1,*,**

* Netherlands Organization for Applied Scientific Research-Prevention and Health, Gaubius Laboratory, Leiden, The Netherlands
{dagger} Department of Human Biology/NUTRIM, Maastricht University, Maastricht, The Netherlands
§ Departments of Cardiology and Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands
** Department of Endocrinology and Diabetes, Leiden University Medical Center, Leiden, The Netherlands

1 To whom correspondence should be addressed. e-mail: pj.voshol{at}pg.tno.nl

Obese obob mice with strong overexpression of the human apolipoprotein C1 (APOC1) exhibit excessive free fatty acid (FFA) and triglyceride (TG) levels and severely reduced body weight (due to the absence of subcutaneous adipose tissue) and skin abnormalities. To evaluate the effects of APOC1 overexpression on hepatic and peripheral insulin sensitivity in a less-extreme model, we generated obob mice with mild overexpression of APOC1 (obob/APOC1+/-) and performed hyperinsulinemic clamp analysis. Compared with obob littermates, obob/APOC1+/- mice showed reduced body weight (-25%) and increased plasma levels of TG (+632%), total cholesterol (+134%), FFA (+65%), glucose (+73%, and insulin (+49%). Hyperinsulinemic clamp analysis revealed severe whole-body and hepatic insulin resistance in obob/APOC1+/- mice and, in addition, increased hepatic uptake of FFA and hepatic TG content. Treatment of obob/APOC1+/- mice with rosiglitazone strongly improved whole-body insulin sensitivity as well as hepatic insulin sensitivity, despite a further increase of hepatic fatty acid (FA) uptake and a panlobular increase of hepatic TG accumulation.

We conclude that overexpression of APOC1 prevents rosiglitazone-induced peripheral FA uptake leading to severe hepatic steatosis. Interestingly, despite rosiglitazone-induced hepatic steatosis, hepatic insulin sensitivity improves dramatically. We hypothesize that the different hepatic fat accumulation and/or decrease in FA intermediates has a major effect on the insulin sensitivity of the liver.

Supplementary key words free fatty acid metabolism • lipid metabolism • hepatic fat accumulation • rosiglitazone • peroxisome proliferator-activated receptor-{gamma}


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


This article has been cited by other articles:


Home page
 EndocrinologyHome page
M. A. M. den Boer, P. J. Voshol, J. P. Schroder-van der Elst, E. Korsheninnikova, D. M. Ouwens, F. Kuipers, L. M. Havekes, and J. A. Romijn
Endogenous Interleukin-10 Protects against Hepatic Steatosis but Does Not Improve Insulin Sensitivity during High-Fat Feeding in Mice
Endocrinology, October 1, 2006; 147(10): 4553 - 4558.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
J. Li, M. Bosch-Marce, A. Nanayakkara, V. Savransky, S. K. Fried, G. L. Semenza, and V. Y. Polotsky
Altered metabolic responses to intermittent hypoxia in mice with partial deficiency of hypoxia-inducible factor-1{alpha}
Physiol Genomics, May 16, 2006; 25(3): 450 - 457.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. W. Bradbury
Lipid Metabolism and Liver Inflammation. I. Hepatic fatty acid uptake: possible role in steatosis
Am J Physiol Gastrointest Liver Physiol, February 1, 2006; 290(2): G194 - G198.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
A. M. van den Hoek, P. J. Voshol, B. N. Karnekamp, R. M. Buijs, J. A. Romijn, L. M. Havekes, and H. Pijl
Intracerebroventricular Neuropeptide Y Infusion Precludes Inhibition of Glucose and VLDL Production by Insulin
Diabetes, October 1, 2004; 53(10): 2529 - 2534.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.