Feed Your Head: Neurodevelopmental Control of Feeding and Metabolism

Abstract

During critical periods of development early in life, excessive or scarce nutritional environments can disrupt the development of central feeding and metabolic neural circuitry, leading to obesity and metabolic disorders in adulthood. A better understanding of the genetic networks that control the development of feeding and metabolic neural circuits, along with knowledge of how and where dietary signals disrupt this process, can serve as the basis for future therapies aimed at reversing the public health crisis that is now building as a result of the global obesity epidemic. This review of animal and human studies highlights recent insights into the molecular mechanisms that regulate the development of central feeding circuitries, the mechanisms by which gestational and early postnatal nutritional status affects this process, and approaches aimed at counteracting the deleterious effects of early over- and underfeeding.

Specification of Select Hypothalamic Circuits and Innate Behaviors by the Embryonic Patterning Gene Dbx1

“…Shh, BMPs, Wnts) and intrinsic (e.g. bHLH and homeodomain-containing transcription factors such as Lhx2 , Rax , Nkx2.1 , Mash1 and Otp ) factors are essential for either regional patterning of the hypothalamus or specification of neuronal subpopulations (Caqueret et al, 2006; McNay et al, 2006; Lu et al, 2013; Peng et al, 2012; Shimogori et al, 2010; Szabó et al, 2009; Wang et al, 2012; Wolf and Ryu, 2013; reviewed in Hoch et al, 2009; Kaji and Nonogaki, 2013; Lee and Blackshaw, 2014; Salvatierra et al, 2014). Here, we find that Dbx1 is required for the specification of orexigenic Npy+/Agrp+ neurons in the Arc and Pmch+ and Hcrt+ output neurons in the LH.…”

Tanycytes: A rich morphological history to underpin future molecular and physiological investigations

“…226,227 It was recently suggested that newly born cells may participate in the regulation of energy metabolism. There is some evidence that hypothalamic neurogenesis is regulated by various physiological factors and pathophysiological conditions.…”

“…There is some evidence that hypothalamic neurogenesis is regulated by various physiological factors and pathophysiological conditions. 226,227 It was recently suggested that newly born cells may participate in the regulation of energy metabolism. 208,210,211,[226][227][228][229] All other circumventricular organs, in addition to the median eminence, contain neural stem cells.…”

Developmental specification of metabolic circuitry

“…In rats, the peak period of neurogenesis in the ARH is E15, as it is for the DMH and dorsomedial part of the VMH. Factors directing cellular specification and differentiation of specific hypothalamic nuclei are beginning to be identified and excellent reviews detail recent progress(Caqueret et al, 2006; Bedont et al, 2015; Duplan et al, 2009; Lee and Blackshaw, 2014). Particularly good data exist for neurons in the ARH and PVH.…”

“…Deletion of many of the genes involved in specifying neuronal identity lead to perturbations in energy balance regulation, demonstrating the sustained importance of these molecular events in determining metabolic phenotype{Lee:2014cw}. In the future it will be essential to carefully define the molecular pathways leading to neuronal differentiation of key populations of hypothalamic neurons in order to identify possible targets for metabolic imprinting.…”