Leptin Receptor Signaling in POMC Neurons Is Required for Normal Body Weight Homeostasis

Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue RN, Boston, MA 02215, USA.
Neuron (Impact Factor: 15.98). 07/2004; 42(6):983-91. DOI: 10.1016/j.neuron.2004.06.004
Source: PubMed

ABSTRACT Neuroanatomical and electrophysiological studies have shown that hypothalamic POMC neurons are targets of the adipostatic hormone leptin. However, the physiological relevance of leptin signaling in these neurons has not yet been directly tested. Here, using the Cre/loxP system, we critically test the functional importance of leptin action on POMC neurons by deleting leptin receptors specifically from these cells in mice. Mice lacking leptin signaling in POMC neurons are mildly obese, hyperleptinemic, and have altered expression of hypothalamic neuropeptides. In summary, leptin receptors on POMC neurons are required but not solely responsible for leptin's regulation of body weight homeostasis.

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Available from: Robert A McGovern, Aug 15, 2014
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    • "EGFP - TVA signals were colocalized with POMC or AgRP immunoreactivity in the majority ( ∼95% ) of the neurons in the ARC ( Figures 1C , D ) , confirming the accuracy of these two driver mouse lines ( Balthasar et al . , 2004 ; Tong et al . , 2008 ) . Starter neurons were characterized by the coexpression of RV - mCherry and EGFP - TVA , which was restricted within the ARC , unilateral to the injection site ( Figures"
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    • "Various brain regions that express LepRb have been identified as important sites for the ability of leptin to produce anti-obesity effects. These include neurons in the arcuate nucleus (ARC) expressing pro-opiomelanocortin (POMC; Balthasar et al., 2004; Hill et al., 2010) or co-expressing neuropeptide Y (NPY)/agouti-related peptide (AgRP; van de Wall et al., 2008), neurons in the ventromedial hypothalamic nucleus (VMH, also known as VMN; Dhillon et al., 2006; Bingham et al., 2008), neurons in the ventral premammillary nucleus (PMV; Leshan et al., 2012), and neurons in the medial nucleus of solitary tract (NTS) and the area postrema (Hayes et al., 2010). "
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    • "Similarly, optogenetic activation of POMC neurons reduces food intake and body weight, whereas activation of AgRP evokes voracious feeding (Aponte et al., 2011). Accordingly, leptin and insulin receptor signaling in POMC or AgRP neurons is necessary for normal regulation of body weight and glucose homeostasis (Balthasar et al., 2004; Kitamura et al., 2006; van de Wall et al., 2008; Belgardt et al., 2008; Xu et al., 2007). "
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