Peripheral ghrelin deepens torpor bouts in mice through the arcuate nucleus neuropeptide Y signaling pathway.
Many small mammals have the ability to enter torpor, characterized by a controlled drop in body temperature (T(b)). We hypothesized that ghrelin would modulate torpor bouts, because torpor is induced by fasting in mice coincident with elevated circulating ghrelin. Female National Institutes of Health (NIH) Swiss mice were implanted with a T(b) telemeter and housed at an ambient temperature (T(a)) of 18 degrees C. On fasting, all mice entered a bout of torpor (minimum T(b): 23.8 +/- 2.0 degrees C). Peripheral ghrelin administration (100 mug) during fasting significantly deepened the bout of torpor (T(b) minimum: 19.4 +/- 0.5 degrees C). When the arcuate nucleus (ARC) of the hypothalamus, a ghrelin receptor-rich region of the brain, was chemically ablated with monosodium glutamate (MSG), fasted mice failed to enter torpor (minimum T(b) = 31.6 +/- 0.6 degrees C). Furthermore, ghrelin administration had no effect on the T(b) minimum of ARC-ablated mice (31.8 +/- 0.8 degrees C). Two major pathways that regulate food intake reside in the ARC, the anorexigenic alpha-melanocyte stimulating hormone (alpha-MSH) pathway and the orexigenic neuropeptide Y (NPY) signaling pathway. Both A(y) mice, which have the alpha-MSH pathway blocked, and Npy -/- mice exhibited shallow, aborted torpor bouts in response to fasting (T(b) minimum: 29.1 +/- 0.6 degrees C and 29.9 +/- 1.2 degrees C, respectively). Ghrelin deepened torpor in A(y) mice (T(b) minimum: 22.8 +/- 1.3 degrees C), but had no effect in Npy -/- mice (T(b) minimum: 29.5 +/- 0.8 degrees C). Collectively, these data suggest that ghrelin's actions on torpor are mediated via NPY neurons within the ARC.[1]References
- Peripheral ghrelin deepens torpor bouts in mice through the arcuate nucleus neuropeptide Y signaling pathway. Gluck, E.F., Stephens, N., Swoap, S.J. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
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