Editors' ChoiceNeuroscience

Astrocytes Control Appetite

Sci. Signal.  08 Jul 2014:
Vol. 7, Issue 333, pp. ec186
DOI: 10.1126/scisignal.2005662

Leptin is a hormone produced in the periphery that sends satiety signals to the brain to reduce food intake. Kim et al. created mice with knockout of the leptin receptor in astrocytes of adults and investigated the effects in the hypothalamic circuits involved in the regulation of eating and compared them with control mice. The total number of astroctyes in the arcuate nucleus region of the hypothalamus was unchanged, but the number and length of the astrocytic processes were reduced in the knockout mice. Coverage and direct contacts between the astrocytes and neurons in the hypothalamus of the knockout mice, including the POMC and AgRP neurons involved in the regulation of feeding, were reduced. In the hypothalamus of the knockout mice, POMC neurons had increased numbers of synapses, increased frequency of miniature inhibitory postsynaptic currents (mIPSCs), and increased amplitude of both mIPSCs and miniature excitatory postsynaptic currents (mEPSCs). In contrast, AgRP neurons of the hypothalamus of the knockout mice had increased frequency of both mIPSCs and mEPSCs, without any change in the amplitude. The knockout mice exhibited less reduction in feeding in response to leptin injection than did control mice, and leptin-stimulated transcription of Fos was also reduced in the knockout mice. Feeding in response to fasting or the hormone ghrelin was also increased in the knockout mice compared with that in control mice. Thus, leptin signaling in astrocytes in the region of the brain that controls appetite is necessary for the neuronal response to hormones that signal satiety or hunger.

J. G. Kim, S. Suyama, M. Koch, S. Jin, P. Argente-Arizon, J. Argente, Z.-W. Liu, M. R. Zimmer, J. K. Jeong, K. Szigeti-Buck, Y. Gao, C. Garcia-Caceres, C.-X. Yi, N. Salmaso, F. M. Vaccarino, J. Chowen, S. Diano, M. O. Dietrich, M. H. Tschöp, T. L. Horvath, Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding. Nat. Neurosci. 17, 908–910 (2014). [PubMed]