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


     

Diabetes Publish Ahead of Print published online ahead of print March 10, 2008
DOI: 10.2337/db07-1702
This Article
Right arrow Full Text (PDF)
Right arrow Figures
Right arrow All Versions of this Article:
db07-1702v1
57/6/1482    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
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stafford, J. M.
Right arrow Articles by Niswender, K. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stafford, J. M.
Right arrow Articles by Niswender, K. D.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Original Research

Central nervous system neuropeptide Y signaling modulates VLDL triglyceride secretion.

John M. Stafford1, Fang Yu2, Richard Printz1,,2, Alyssa H. Hasty2, Larry L. Swift3, and Kevin D. Niswender1,,2,,4

1Division of Diabetes, Endocrinology, & Metabolism, Department of Internal Medicine
2Department of Molecular Physiology and Biophysics
3Department of Pathology, Vanderbilt University School of Medicine
4Tennessee Valley Healthcare System

Objective: Elevated triglyceride (TG) is the major plasma lipid abnormality in obese and diabetic patients and contributes to cardiovascular morbidity in these disorders. We sought to identify novel mechanisms leading to hypertriglyceridemia. Resistance to negative feedback signals from adipose tissue in key CNS energy homeostatic circuits contributes to the development of obesity. Because triglyceride (TG) represents both the largest energy depot in the body and is elevated in both the plasma and adipose in obesity and diabetes, we hypothesized that the same neural circuits that regulate energy balance also regulate the secretion of TG into plasma.

Methods: In normal fasting rats, the TG secretion rate was estimated by serial blood sampling after intravascular tyloxapol pre-treatment. NPY signaling in the CNS was modulated by intracerebroventricular (ICV) injection of NPY, receptor antagonist, and receptor agonist.

Results: A single ICV injection of NPY increased TG secretion by 2.5-fold in the absence of food intake, and this was determined to be very-low density lipoprotein (VLDL) by fast protein liquid chromatography (FPLC). This effect was recapitulated by activating NPY signaling in downstream neurons with an NPY-Y5 receptor agonist. An NPY-Y1 receptor antagonist decreased the VLDL-TG secretion rate by 50% compared to vehicle. Increased TG secretion was due to increased secretion of VLDL particles, rather than secretion of larger particles, as apolipoprotein B100 was elevated in FPLC fractions corresponding to VLDL.

Conclusion: We find that a key neuropeptide system involved in energy homeostasis in the CNS exerts control over VLDL-TG secretion into the bloodstream.

Correspondence: kevin.niswender{at}vanderbilt.edu


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
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2008 by the American Diabetes Association.