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


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by O’Rourke, L.
Right arrow Articles by Shepherd, P. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by O’Rourke, L.
Right arrow Articles by Shepherd, P. R.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Diabetes 50:955-961, 2001
© 2001 by the American Diabetes Association, Inc.

Insulin and Leptin Acutely Regulate Cholesterol Ester Metabolism in Macrophages by Novel Signaling Pathways

Lisa O’Rourke1, Steven J. Yeaman2, and Peter R. Shepherd1

1 Department of Biochemistry and Molecular Biology, University College London, London
2 School of Biochemistry and Genetics, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, U.K.

Leptin is produced in adipose tissue and acts in the hypothalamus to regulate food intake. However, recent evidence also indicates a potential for direct roles for leptin in peripheral tissues, including those of the immune system. In this study, we provide direct evidence that macrophages are a target tissue for leptin. We found that J774.2 macrophages express the functional long form of the leptin receptor (ObRb) and that this becomes tyrosine-phosphorylated after stimulation with low doses of leptin. Leptin also stimulates both phosphoinositide 3-kinase (PI 3-kinase) activity and tyrosine phosphorylation of JAK2 and STAT3 in these cells. We investigated the effects of leptin on hormone-sensitive lipase (HSL), which acts as a neutral cholesterol esterase in macrophages and is a rate-limiting step in cholesterol ester breakdown. Leptin significantly increased HSL activity in J774.2 macrophages, and these effects were additive with the effects of cAMP and were blocked by PI 3-kinase inhibitors. Conversely, insulin inhibited HSL in macrophages, but unlike adipocytes, this effect did not require PI 3-kinase. These results indicate that leptin and insulin regulate cholesterol-ester homeostasis in macrophages and, therefore, defects in this process caused by leptin and/or insulin resistance could contribute to the increased incidence of atherosclerosis found associated with obesity and type 2 diabetes.


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?


This article has been cited by other articles:


Home page
 Recent Prog Horm ResHome page
C. Bjorbaek and B. B. Kahn
Leptin Signaling in the Central Nervous System and the Periphery
Recent Prog. Horm. Res., January 1, 2004; 59(1): 305 - 331.
[Abstract] [Full Text]

Home page
 DiabetesHome page
F. Maingrette and G. Renier
Leptin Increases Lipoprotein Lipase Secretion by Macrophages: Involvement of Oxidative Stress and Protein Kinase C
Diabetes, August 1, 2003; 52(8): 2121 - 2128.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
K. Rahmouni, W. G. Haynes, D. A. Morgan, and A. L. Mark
Intracellular Mechanisms Involved in Leptin Regulation of Sympathetic Outflow
Hypertension, March 1, 2003; 41(3): 763 - 767.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
R. Shamir, N. Shehadeh, M. Rosenblat, O. Eshach-Adiv, R. Coleman, M. Kaplan, S. Hamoud, S. Lischinsky, and T. Hayek
Oral Insulin Supplementation Attenuates Atherosclerosis Progression in Apolipoprotein E-Deficient Mice
Arterioscler. Thromb. Vasc. Biol., January 1, 2003; 23(1): 104 - 110.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. O'Rourke, L. M. Gronning, S. J. Yeaman, and P. R. Shepherd
Glucose-dependent Regulation of Cholesterol Ester Metabolism in Macrophages by Insulin and Leptin
J. Biol. Chem., November 1, 2002; 277(45): 42557 - 42562.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
F. B. Kraemer and W.-J. Shen
Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis
J. Lipid Res., October 1, 2002; 43(10): 1585 - 1594.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
R. B. CEDDIA, H. A. KOISTINEN, J. R. ZIERATH, and G. SWEENEY
Analysis of paradoxical observations on the association between leptin and insulin resistance
FASEB J, August 1, 2002; 16(10): 1163 - 1176.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
L. E. Wold, D. P. Relling, J. Duan, F. L. Norby, and J. Ren
Abrogated Leptin-Induced Cardiac Contractile Response in Ventricular Myocytes Under Spontaneous Hypertension: Role of JAK/STAT Pathway
Hypertension, January 1, 2002; 39(1): 69 - 74.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
G. Sweeney, J. Keen, R. Somwar, D. Konrad, R. Garg, and A. Klip
High Leptin Levels Acutely Inhibit Insulin-Stimulated Glucose Uptake without Affecting Glucose Transporter 4 Translocation in L6 Rat Skeletal Muscle Cells
Endocrinology, November 1, 2001; 142(11): 4806 - 4812.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2001 by the American Diabetes Association.