Leptin signaling in the hypothalamus is required for normal food intake and
body weight homeostasis. Recent evidence suggests that besides the signal transducer and activator of transcription-3 (STAT3) pathway, several non-STAT3 pathways mediate
leptin signaling in the hypothalamus. We have previously demonstrated that
leptin stimulates phosphodiesterase-3B (PDE3B) activity in the hypothalamus, and
PDE3 inhibitor cilostamide reverses
anorectic and
body weight reducing effects of
leptin. To establish the physiological role of PDE3B signaling in the hypothalamus, we examined if
leptin signaling through the PDE3B pathway is responsible for the activation of
proopiomelanocortin (
POMC) and
neurotensin (NT) neurons, which are known to play a critical role in energy homeostasis. To this end, we assessed the effect of
cilostamide on
leptin-induced
POMC and NT gene expression in the rat hypothalamus. Results showed that while central injection of
leptin significantly increased both
POMC and NT
mRNA levels in the medial basal hypothalamus,
cilostamide completely reversed this effect of
leptin suggesting a PDE3B-activation dependent induction of
POMC and NT gene expression by
leptin. This result further suggests that the PDE3B pathway plays an important role in mediating
leptin action in the hypothalamus.