AstroGenesis: And there was leptin on the sixthday.

Abstract

In the central nervous system (CNS), the hypothalamus plays a fundamental role in controlling food intake and energy expenditure as well as glucose homeostasis. Alterations in this control can lead to obesity, glucose intolerance and type 2 diabetes in both rodents and humans [1]. The past two decades have witnessed major advances in our understanding of the control of energy balance by hypothalamic neuronal populations. These neurons respond to peripherally-derived metabolic signals to elicit adaptive behavioral and physiological responses in order to maintain body weight. Leptin, the most notorious adipose-derived hormone, targets neurons of the hypothalamus, notably orexigenic agouti-related protein (AgRP) and anorexigenic proopiomelanocortin (POMC) neurons of the arcuate nucleus (ARC), to decrease feeding and increase energy expenditure. Leptin binding to its receptor (LepR) in ARC neurons regulates neuronal activity and synaptic plasticity by activating signaling pathways that include phosphonositide 3-kinase (PI3K), extracellular signal-regulated kinases (ERK), AMP-activated protein kinase and signal transducer and activator of transcription 3 (STAT3) [1]. Leptin deficiency or loss-offunction mutations in the LepR lead to hyperphagia and obesity in both rodents and humans illustrating the critical role of leptin signaling in central control of energy homeostasis. In addition to the wellestablished actions of leptin on metabolic neurocircuits, nonneuronal cells of the hypothalamus have recently emerged as new targets and mediators of leptin effects on energy balance [2,3]. In this issue of Molecular Metabolism, Rottkamp et al. add a brand new element to the leptin signaling puzzle with demonstration that leptin enhances astrocytes proliferation in the hypothalamus during postnatal development [4]. During CNS development, neurons and glial cells are sequentially generated. Neurogenesis occurs during prenatal brain development and most neurons of the adult brain are already produced at birth. In contrast, glial cells are generated after the end of the first postnatal week and account for more than half of brain cells in adults. Astrocytes, the most abundant glial cells in the brain, provide anatomical and metabolic support for neurons. In addition, they regulate several neuronal processes including proliferation, differentiation and synaptogenesis. Recent evidence suggests that hypothalamic astrocytes