Brain Apolipoprotein E: an Important Regulator of Food Intake in Rats

  1. Ling Shen12,
  2. Patrick Tso12,
  3. Stephen C. Woods13,
  4. Deborah J. Clegg13,
  5. Kyna L. Barber2,
  6. Katherine Carey12 and
  7. Min Liu12
  1. 1Cincinnati Obesity Research Center, University of Cincinnati College of Medicine, Cincinnati, Ohio
  2. 2Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio
  3. 3Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio
  1. Corresponding author: Min Liu, lium{at}uc.edu

Abstract

OBJECTIVE—The worldwide prevalence of obesity is increasing at an alarming rate, along with the associated increased rates of type 2 diabetes, heart disease, and some cancers. While efforts to address environmental factors responsible for the recent epidemic must continue, investigation into the anorectic functions of potential molecules we present here, such as apolipoprotein (apo)E, offers exciting possibilities for future development of successful anti-obesity therapies.

RESEARCH DESIGN AND METHODS—Changes in feeding behavior after intracerebroventricular injection of apoE, the regulation of hypothalamic apoE gene expression by energy status, and the interaction of hypothalamic apoE with other neuropeptides were studied.

RESULTS—Intracerebroventricular apoE significantly decreased food intake without causing malaise, whereas intracerebroventricular infusion of apoE antiserum stimulated feeding, implying that endogenous apoE tonically inhibits food intake. Consistent with this, apoE was present in the hypothalamus, a brain site intimately involved in the integration of signals for energy homeostasis. Fasted rats exhibited significantly decreased apoE gene expression in the hypothalamus, and refeeding of these rats for 4 h evoked a significant increase of hypothalamic apoE mRNA levels. Both genetically obese (ob/ob) mice and rats with high-fat diet–induced obesity had significantly reduced hypothalamic apoE mRNA levels compared with their lean control counterparts, suggesting that decreased apoE may contribute to hyperphagia in these obese animals. Additionally, apoE-stimulated hypothalamic proopiomelanocortin gene expression and SHU9119, a melanocortin 3/4 receptor antagonist, attenuated the inhibitory function of apoE on feeding.

CONCLUSIONS—These data demonstrate that apoE suppresses food intake via a mechanism enhancing melanocortin signaling in the hypothalamus.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 16 June 2008.

  • Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted May 15, 2008.
    • Received February 28, 2008.
« Previous | Next Article »Table of Contents

This Article

  1. Published online before print June 16, 2008, doi: 10.2337/db08-0291 Diabetes August 2008 vol. 57 no. 8 2092-2098
  1. » Abstract
  2. Full Text
  3. Full Text (PDF)
  4. All Versions of this Article:
    1. db08-0291v1
    2. 57/8/2092 most recent

Current Issue

  1. November 2009, 58 (11)
    Current Issue
  1. Alert me to new issues of Diabetes