High Fat Diet Multigenerationally Affects Hippocampal Neural Stem Cell Proliferation via Epigenetic Mechanisms

Francesca Natale; Matteo Spinelli; Saviana Antonella Barbati; Lucia Leone; Salvatore Fusco; Claudio Grassi

doi:10.3390/cells11172661

High Fat Diet Multigenerationally Affects Hippocampal Neural Stem Cell Proliferation via Epigenetic Mechanisms

Cells. 2022 Aug 27;11(17):2661. doi: 10.3390/cells11172661.

Authors

Francesca Natale^{1

2}, Matteo Spinelli^{1

2}, Saviana Antonella Barbati¹, Lucia Leone^{1

2}, Salvatore Fusco^{1

2}, Claudio Grassi^{1

2}

Affiliations

¹ Department of Neuroscience, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
² Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

Abstract

Early-life metabolic stress has been demonstrated to affect brain development, persistently influence brain plasticity and to exert multigenerational effects on cognitive functions. However, the impact of an ancestor's diet on the adult neurogenesis of their descendants has not yet been investigated. Here, we studied the effects of maternal high fat diet (HFD) on hippocampal adult neurogenesis and the proliferation of neural stem and progenitor cells (NSPCs) derived from the hippocampus of both the second and the third generations of progeny (F2_HFD and F3_HFD). Maternal HFD caused a multigenerational depletion of neurogenic niche in F2_HFD and F3_HFD mice. Moreover, NSPCs derived from HFD descendants showed altered expression of genes regulating stem cell proliferation and neurodifferentiation (i.e., Hes1, NeuroD1, Bdnf). Finally, ancestor HFD-related hyper-activation of both STAT3 and STAT5 induced enhancement of their binding on the regulatory sequences of Gfap gene and an epigenetic switch from permissive to repressive chromatin on the promoter of the NeuroD1 gene. Collectively, our data indicate that maternal HFD multigenerationally affects hippocampal adult neurogenesis via an epigenetic derangement of pro-neurogenic gene expression in NSPCs.

Keywords: epigenetics; hippocampal adult neurogenesis; maternal HFD; neural stem and progenitor cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Proliferation
Diet, High-Fat* / adverse effects
Epigenesis, Genetic
Hippocampus* / metabolism
Mice
Mice, Inbred C57BL

Grants and funding

This research was funded by the Italian Ministry of University and Research (SIR 2014 RBSI14ZV59 to S.F.) and by Ministero della Salute—Ricerca Corrente 2022 Fondazione Policlinico Universitario A. Gemelli IRCCS (to C.G.).