AI Article Synopsis
- Mice without the RIIβ regulatory subunit show less body fat and are more resistant to gaining weight on a high-calorie diet.
- RIIβ knockout mice respond more effectively to leptin, which enhances their feeding regulation and energy metabolism, due to prolonged JAK/STAT3 signaling and reduced Socs3 levels in the hypothalamus.
- Activation of PKA in RIIβ knockout mice is diminished during fasting, implying that RIIβ-PKA influences how long leptin signaling lasts, affecting the body's ability to manage energy and weight.
Article Abstract
Mice lacking the RIIβ regulatory subunit of cyclic AMP-dependent protein kinase A (PKA) display reduced adiposity and resistance to diet-induced obesity. Here we show that RIIβ 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 RIIβ KO mice. During fasting, RIIβ-PKA is activated and this correlates with an increase in CREB phosphorylation. The increase in CREB phosphorylation is absent in the fasted RIIβ KO hypothalamus. Selective inhibition of PKA activity in AgRP neurons partially recapitulates the leanness and resistance to diet-induced obesity of RIIβ KO mice. Our findings suggest that RIIβ-PKA modulates the duration of leptin receptor signalling and therefore the magnitude of the catabolic response to leptin.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4576457 | PMC |
| http://dx.doi.org/10.1038/ncomms9237 | DOI Listing |
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