Leptin insensitivity and nuclei-specific altered gene expression in hypothalamus of transgenic mice with chronic hyperprolactinemia

GUILLERMINA MARÍA LUQUE; MARÍA FELICITAS LÓPEZ VICCHI; DAVID GRATTAN; SHARON LADYMAN; DAMASIA BECU-VILLALOBOS; ANA MARÍA ORNSTEIN

Chicago

Congreso; ENDO2018; 2018

Hypothalamic circuits are paramount in maintaining energy homeostasis, and hyperprolactinemia has been associated with increased food intake acting at a central level. In order to unravel the participation of specific hypothalamic nuclei targeted by prolactin, we studied the effect of lifelong hyperprolactinemia in female mice that selectively lack dopamine type 2 receptors from lactotropes (lacDrd2KO) on hypothalamic gene expression and leptin signaling activation within specific hypothalamic nuclei. We dissected the arcuate nucleus (ARN), ventromedial hypothalamus (VMH), dorsomedial hypothalamus (DMH), paraventricular nucleus (PVN), anteroventral periventricular nucleus (AVPV) where prolactin could be potentially regulating metabolism, and evaluated specific mRNA expression and STAT3 activation. Leptin, a hormone produced by white adipose tissue inhibits orexigenic peptide NPY brain expression. Ten-month-old ad libitum lacDrd2KO mice show increased total hypothalamic Npy mRNA levels compared to Drd2loxP/loxP controls despite a five-fold increase in serum leptin levels (p