Early-life exposure to XXXX programs the hypothalamic melanocortin system.

@entity172 @entity251 @entity586 @entity11982 @entity28 @entity19 @entity10433 @entity342 @entity587 @entity1019
In mammals, males consume more food, which is considered a masculinized behavior, but the underlying mechanism of this sex-specific feeding behavior is unknown. In @entity19 , neonatal @entity251 (NT) is critical to masculinize the developing brain, leading to sex differences in reproductive physiology. The proopiomelanocortin ( @entity11982 ) neurons of the hypothalamic @entity1019 ( @entity1019 ) are critical to suppress energy intake and @entity11982 innervation of hypothalamic feeding circuits develops to a large extent neonatally. We hypothesized that NT programs the masculinization of energy intake by programming @entity11982 neurons. We tested this hypothesis by comparing control females and control males (CMs) with female @entity19 neonatally androgenized with @entity251 (NTFs). We show that increased food intake in CMs is associated with reduced @entity11982 expression and decreased intensity of neuronal projections from @entity11982 neurons within the @entity1019 compared with control females. We found that NTFs display a masculinized energy intake and @entity1019 @entity11982 expression and innervation as observed in CMs, which can be mimicked by neonatal exposure to the @entity342 receptor agonist @entity586 ( @entity587 ). NTFs also exhibit hyperleptinemia and a decreased ability of leptin to up-regulate @entity11982 , suppress food intake, and prevent adipose tissue accumulation, independent of @entity10433 . However, this leptin resistance is specific to NTFs, is not a consequence of masculinization, and is reproduced by neonatal exposure to @entity172 but not @entity587 . Thus, NT programs a sexual differentiation of @entity11982 neurons in female @entity19 via @entity587 but also predisposes to leptin resistance and @entity28 in an @entity172 -dependent manner.
