Activation ofGPR40 induces hypothalamic neurogenesis through p38‐ and BDNF‐dependent mechanisms.
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2020
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Abstract
Hypothalamic adult neurogenesis provides the basis for renewal of neurons involved in the regulation
of whole-body energy status. In addition to hormones, cytokines and growth factors, components of
the diet, particularly fatty acids, have been shown to stimulate hypothalamic neurogenesis; however,
the mechanisms behind this action are unknown. Here, we hypothesized that GPR40 (FFAR1), the
receptor for medium and long chain unsaturated fatty acids, could mediate at least part of the
neurogenic activity in the hypothalamus. We show that a GPR40 ligand increased hypothalamic
cell proliferation and survival in adult mice. In postnatal generated neurospheres, acting in synergy
with brain-derived neurotrophic factor (BDNF) and interleukin 6, GPR40 activation increased the
expression of doublecortin during the early diferentiation phase and of the mature neuronal
marker, microtubule-associated protein 2 (MAP2), during the late diferentiation phase. In Neuro-2a
proliferative cell-line GPR40 activation increased BDNF expression and p38 activation. The chemical
inhibition of p38 abolished GPR40 efect in inducing neurogenesis markers in neurospheres, whereas
BDNF immunoneutralization inhibited GPR40-induced cell proliferation in the hypothalamus of
adult mice. Thus, GPR40 acts through p38 and BDNF to induce hypothalamic neurogenesis. This
study provides mechanistic advance in the understating of how a fatty acid receptor regulates adult
hypothalamic neurogenesis.
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ENGEL, D. F. et al. Activation ofGPR40 induces hypothalamic neurogenesis through p38‐ and BDNF‐dependent mechanisms. Scientific Reports, v. 10, 2020. Disponível em: <https://www.nature.com/articles/s41598-020-68110-2>. Acesso em: 11 out. 2022.