Brain apolipoprotein E: An important regulator of food intake and body weight

Abstract

The hypothalamus regulates ingestive behavior through multiple signaling systems. Here we report that apolipoprotein E (apoE) plays an important role in the regulation of food intake and body weight. Administration of apoE into the 3rd ventricle (i3vt) significantly decreased food intake and body weight in rats without causing malaise, whereas i3vt infusion of apoE antiserum stimulated feeding, implying that endogenous apoE tonically inhibits food intake. Consistent with this, apoE, as revealed by immunohistochemistry, 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 evokes a significant increase of hypothalamic apoE mRNA levels. Both genetically obese ( ob/ob) mice and high-fat diet-induced-obese rats had significantly reduced hypothalamic apoE mRNA levels, compared with their lean controls, suggesting that decreased apoE may contribute to hyperphagia in these obese animals. Additionally, our findings that apoE stimulated hypothalamic proopiomelanocortin gene expression in fasted rats and that SHU9119, a melanocortin 3/4 receptor antagonist, attenuated apoE's inhibition of feeding, suggest that apoE's anorectic action is associated with brain melanocortin signaling. Taken together, all of these findings demonstrate that brain apoE is an important regulator of food intake and body weight.