Brain Apolipoprotein E: an Important Regulator of Food Intake in Rats
Open Access
- 1 August 2008
- journal article
- Published by American Diabetes Association in Diabetes
- Vol. 57 (8), 2092-2098
- https://doi.org/10.2337/db08-0291
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.Keywords
This publication has 34 references indexed in Scilit:
- Blocking the apolipoprotein E/amyloid-β interaction as a potential therapeutic approach for Alzheimer's diseaseProceedings of the National Academy of Sciences of the United States of America, 2006
- Apolipoprotein A-IV interacts synergistically with melanocortins to reduce food intakeAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2006
- Apolipoprotein E inhibition of vascular hyperplasia and neointima formation requires inducible nitric oxide synthaseJournal of Lipid Research, 2005
- Functions of lipoprotein receptors in neuronsJournal of Lipid Research, 2004
- Rodent obesity models: An overviewExperimental and Clinical Endocrinology & Diabetes, 2001
- Apolipoprotein E: a major piece in the Alzheimer's disease puzzleJournal of Cellular and Molecular Medicine, 2001
- Evidence That the Diabetes Gene Encodes the Leptin Receptor: Identification of a Mutation in the Leptin Receptor Gene in db/db MiceCell, 1996
- Abnormal splicing of the leptin receptor in diabetic miceNature, 1996
- A comparison between effects of intraventricular insulin and intraperitoneal lithium chloride on three measures sensitive to emetic agents.Behavioral Neuroscience, 1995
- Isolation and Partial Characterization of an Arginine-Rich Apolipoprotein from Human Plasma Very-Low-Density Lipoproteins: Apolipoprotein EHoppe-Seyler´s Zeitschrift für physiologische Chemie, 1975