The activation of
proopiomelanocortin (
POMC) neurons in different regions of the brain, including the arcuate nucleus of the hypothalamus (
ARC) and the nucleus of the solitary tract curtails feeding and attenuates
body weight. In this study, we compared the effects of delivery of a recombinant adeno-associated viral (rAAV) construct encoding
POMC to the
ARC with delivery to the ventral tegmental area (VTA). F344×Brown Norway rats were high-fat (HF) fed for 14 days after which self-complementary rAAV constructs expressing either
green fluorescent protein or the
POMC gene were injected using coordinates targeting either the VTA or the
ARC. Corresponding increased
POMC levels were found at the predicted injection sites and subsequent α-
melanocyte-stimulating hormone levels were observed. Food intake and
body weight were measured for 4 months. Although caloric intake was unaltered by
POMC overexpression,
weight gain was tempered with
POMC overexpression in either the VTA or the
ARC compared with controls. There were parallel decreases in adipose tissue reserves. In addition, levels of oxygen consumption and
brown adipose tissue uncoupling protein 1 were significantly elevated with
POMC treatment in the VTA. Interestingly,
tyrosine hydroxylase levels were increased in both the
ARC and VTA with
POMC overexpression in either the
ARC or the VTA. In conclusion, these data indicate a role for
POMC overexpression within the VTA reward center to combat HF-induced
obesity.