| First Author | Yang L | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 8237 | PubMed ID | 26381935 |
| Mgi Jnum | J:226986 | Mgi Id | MGI:5699486 |
| Doi | 10.1038/ncomms9237 | Citation | Yang L, et al. (2015) Hypothalamic PKA regulates leptin sensitivity and adiposity. Nat Commun 6:8237 |
| abstractText | Mice lacking the RIIbeta regulatory subunit of cyclic AMP-dependent protein kinase A (PKA) display reduced adiposity and resistance to diet-induced obesity. Here we show that RIIbeta knockout (KO) mice have enhanced sensitivity to leptin's effects on both feeding and energy metabolism. After administration of a low dose of leptin, the duration of hypothalamic JAK/STAT3 signalling is increased, resulting in enhanced POMC mRNA induction. Consistent with the extended JAK/STAT3 activation, we find that the negative feedback regulator of leptin receptor signalling, Socs3, is inhibited in the hypothalamus of RIIbeta KO mice. During fasting, RIIbeta-PKA is activated and this correlates with an increase in CREB phosphorylation. The increase in CREB phosphorylation is absent in the fasted RIIbeta KO hypothalamus. Selective inhibition of PKA activity in AgRP neurons partially recapitulates the leanness and resistance to diet-induced obesity of RIIbeta KO mice. Our findings suggest that RIIbeta-PKA modulates the duration of leptin receptor signalling and therefore the magnitude of the catabolic response to leptin. |
