Review
Role of hypothalamic neurogenesis in feeding regulation

https://doi.org/10.1016/j.tem.2013.10.005Get rights and content

Highlights

  • The hypothalamus is a neurogenic niche in the adult mammalian brain.

  • Adult hypothalamic neurogenesis contributes to the regulation of energy-balance.

  • Hypothalamic neurogenesis is affected by metabolic disorders such as obesity.

  • Embryonic hypothalamic neurogenesis influences feeding regulation during adulthood.

The recently described generation of new neurons in the adult hypothalamus, the center for energy regulation, suggests that hypothalamic neurogenesis is a crucial part of the mechanisms that regulate food intake. Accordingly, neurogenesis in both the adult and embryonic hypothalamus is affected by nutritional cues and metabolic disorders such as obesity, with consequent effects on energy-balance. This review critically discusses recent findings on the contribution of adult hypothalamic neurogenesis to feeding regulation, the impact of energy-balance disorders on adult hypothalamic neurogenesis, and the influence of embryonic hypothalamic neurogenesis upon feeding regulation in the adult. Understanding how hypothalamic neurogenesis contributes to food intake control will change the paradigm on how we perceive energy-balance regulation.

Section snippets

Neurogenesis in the adult brain

Neurogenesis is a complex and highly regulated process that results in the production of new neurons (see Glossary). Neurogenesis occurs at high rates during the embryonic period when substantial quantities of new cells are generated by the proliferation of neuroprogenitor cells (NPCs), and subsequently migrate to the developing tissue [1]. In the adult, neurogenesis occurs at low rates in discrete regions of the brain such as the subventricular zone (SVZ) of the lateral ventricles and the

Hypothalamus and feeding regulation

Feeding behavior and energy-balance are regulated centrally by the hypothalamus. Distinct nuclei within the hypothalamus, including the arcuate nucleus (ARC), the paraventricular nucleus (PVN), the ventromedial (VMH) and dorsomedial (DMH) hypothalamus, and the lateral hypothalamic area, share neuronal interconnections and together they maintain body homeostasis [4]. ARC neurons produce the orexigenic neuropeptides neuropeptide Y (NPY) and agouti-related protein (AgRP) that act to increase food

Cell populations during embryonic hypothalamic neurogenesis

The development of hypothalamic feeding circuits starts during the embryonic period and, in rodents, continues through the first 2 weeks of postnatal life [10]. Recent studies show that hypothalamic NPCs are present in the embryonic hypothalamus; for example, in rodents, POMC and NPY neuroprecursors are identified as early as embryonic (E) days E10.5 and E14.5, respectively 11, 12. In agreement, NPCs isolated from fetal rat hypothalamus express neuropeptides NPY, AgRP, and POMC [13].

Adult hypothalamic neurogenesis

Emerging evidence suggests that, in addition to the SVZ and SGZ zones, active neurogenesis takes place in other regions of the adult rodent brain 33, 34, 35, 36. These regions include the hypothalamus where a potential neurogenic niche has been characterized 8, 37, 38, 39, 40. Some reports suggest that the basal (unstimulated) levels of neurogenesis in the hypothalamus are low 37, 38, 40, and are probably less than those seen in well-established neurogenic zones [35]. However, recent papers

Concluding remarks

The concept of adult hypothalamic neurogenesis has changed the paradigm of how we understand energy-balance regulation. It is now widely accepted that neurogenic processes occurring in the adult rodent hypothalamus contribute to the physiological regulation of food intake and body weight. Mechanistically, this neuronal plasticity offers the organism flexibility to respond/adapt to daily metabolic challenges. However, the exact role of adult hypothalamic neurogenesis in feeding regulation can

Acknowledgments

We thank the FCT (Portuguese Foundation for Science and Technology), FEDER (Fundo Europeu de Desenvolvimento Regional), and COMPETE (Programa Operacional Factores de Competitividade) for financial support (SFRH/BPD/4/2011; PEst-C/SAU/LA0001/2013-2014; PTDC/SAU-FCF/099082/2008).

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