AJP - GI AJP: Endocrinology and Metabolism
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Gastrointest Liver Physiol (July 31, 2008). doi:10.1152/ajpgi.90204.2008
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
295/3/G621    most recent
ajpgi.90204.2008v1
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Varela, G. M.
Right arrow Articles by Ahima, R. S
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Varela, G. M.
Right arrow Articles by Ahima, R. S
Submitted on February 21, 2008
Revised on July 10, 2008
Accepted on July 23, 2008

Inhibition of ADRP prevents diet-induced insulin resistance

Gladys M. Varela1, Daniel A. Antwi1, Ravindra Dihr1, Xiaoyan Yin1, Neel S. Singhal1, Mark J. Graham2, Roseanne M. Crooke2, and Rexford S Ahima1*

1 University of Pennsylvania
2 Isis Pharmaceuticals

* To whom correspondence should be addressed. E-mail: ahima{at}mail.med.upenn.edu.

Diets with high fat content induce steatosis, insulin resistance and type 2 diabetes. The lipid droplet protein, Adipose Differentiation-Related Protein (ADRP), mediates hepatic steatosis but whether this affects insulin action in the liver or peripheral organs in diet-induced obesity is uncertain. We fed C57BL/6J mice a high-fat diet and simultaneously treated them with an antisense oligonucleotide (ASO) against ADRP for 4 weeks. Glucose homeostasis was assessed using clamp and tracer techniques. ADRP ASO decreased the levels of triglycerides and diacylglycerol in the liver, but fatty acids, long chain fatty acyl CoAs, ceramides and cholesterol were unchanged. Insulin action in the liver was enhanced following ADRP ASO treatment, whereas muscle and adipose tissue were not affected. ADRP ASO increased the phosphorylation IRS1, IRS2 and Akt, and decreased gluconeogenic enzymes and PKC{varepsilon}, consistent with its insulin sensitizing action. These results demonstrate an important role for ADRP in the pathogenesis of diet-induced insulin resistance.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
R. C. R. Meex, P. Schrauwen, and M. K. C. Hesselink
Modulation of myocellular fat stores: lipid droplet dynamics in health and disease
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2009; 297(4): R913 - R924.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
J. M. Sapiro, M. T. Mashek, A. S. Greenberg, and D. G. Mashek
Hepatic triacylglycerol hydrolysis regulates peroxisome proliferator-activated receptor {alpha} activity
J. Lipid Res., August 1, 2009; 50(8): 1621 - 1629.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
B. Fan, S. Ikuyama, J.-Q. Gu, P. Wei, J.-i. Oyama, T. Inoguchi, and J. Nishimura
Oleic acid-induced ADRP expression requires both AP-1 and PPAR response elements, and is reduced by Pycnogenol through mRNA degradation in NMuLi liver cells
Am J Physiol Endocrinol Metab, July 1, 2009; 297(1): E112 - E123.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.