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Maternal High Fat Diet Multigenerationally Impairs Hippocampal Adult Neurogenesis †

Department of Neuroscience, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Author to whom correspondence should be addressed.
Presented at Cells, Cells and Nothing but Cells: Discoveries, Challenges and Directions, 6–8 March 2023; Available online:
Biol. Life Sci. Forum 2023, 21(1), 3;
Published: 17 March 2023


Metabolic dysregulation harms brain health. Early-life (pre- and perinatal) dysmetabolic stimuli have been demonstrated to affect central nervous system (CNS), multigenerationally impairing brain plasticity and cognitive functions in adult offsprings. In our previous work, we reported that maternal high fat diet (HFD) impaired synaptic plasticity, learning and memory of descendants until the third generation. Neural stem and progenitor cells (NSPCs) represent the cellular source of newborn neurons in the subgranular zone of the hippocampus, and their fate is finely modulated by metabolic signals. Epigenetic mechanisms are key factors controlling the neural fate of NSPCs and they dynamically regulate CNS development and adult neurogenesis. Here, we demonstrate that progenitor HFD altered both the proliferation of NSPCs and the hippocampal adult neurogenesis on second and third generations of progeny (F2HFD and F3HFD), leading to the depletion of neurogenic niche in the descendants. Moreover, in NSPCs isolated from the hippocampus of HFD descendants we found reduced expression of genes regulating stem cell proliferation and neuro-differentiation (i.e., Hes1, NeuroD1, Bdnf). Furthermore, maternal HFD-related metabolic stress induced a rearrangement of STAT3/5 transcription factors occurring on the regulatory sequences of NeuroD1 and Gfap genes, causing the epigenetic repression of pro-neurogenic and the activation of pro-glial differentiation genes. Collectively, our data indicate that maternal HFD multigenerationally impairs hippocampal neural stem cell niche via epigenetic inhibition of pro-neurogenic gene expression in NSPCs.

Author Contributions

Conceptualization, S.F. and C.G.; formal analysis, S.F.; funding acquisition, S.F. and C.G.; investigation, F.N., M.S. and S.A.B.; methodology, L.L. and S.F.; project administration, S.F.; supervision, S.F. and C.G.; validation, F.N. and M.S.; visualization, F.N.; writing—original draft, F.N. and S.F.; writing—review and editing, S.F. and C.G. All authors have read and agreed to the published version of the manuscript.


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.).

Institutional Review Board Statement

The animal study protocol was approved by the Ethics Committee of Università Cattolica del Sacro Cuore (authorization n. 39/2017-PR of 16 January 2017) and were fully compliant with Italian (Ministry of Health guidelines, Legislative Decree No. 116/1992) and European Union (Directive No. 86/609/EEC) legislations on animal research. The methods were carried out in strict accordance with the approved guidelines.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available as Ref. [1].

Conflicts of Interest

The authors declare no conflict of interest.


  1. Natale, F.; Spinelli, M.; Barbati, S.A.; Leone, L.; Fusco, S.; Grassi, C. High Fat Diet Multigenerationally Affects Hippocampal Neural Stem Cell Proliferation via Epigenetic Mechanisms. Cells 2022, 11, 2661. [Google Scholar] [CrossRef] [PubMed]
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MDPI and ACS Style

Natale, F.; Spinelli, M.; Barbati, S.A.; Leone, L.; Fusco, S.; Grassi, C. Maternal High Fat Diet Multigenerationally Impairs Hippocampal Adult Neurogenesis. Biol. Life Sci. Forum 2023, 21, 3.

AMA Style

Natale F, Spinelli M, Barbati SA, Leone L, Fusco S, Grassi C. Maternal High Fat Diet Multigenerationally Impairs Hippocampal Adult Neurogenesis. Biology and Life Sciences Forum. 2023; 21(1):3.

Chicago/Turabian Style

Natale, Francesca, Matteo Spinelli, Saviana Antonella Barbati, Lucia Leone, Salvatore Fusco, and Claudio Grassi. 2023. "Maternal High Fat Diet Multigenerationally Impairs Hippocampal Adult Neurogenesis" Biology and Life Sciences Forum 21, no. 1: 3.

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