Maternal dietary fat during lactation shapes single nucleus transcriptomic profile of postnatal offspring hypothalamus in a sexually dimorphic manner in mice

Yi Huang; Anyongqi Wang; Wenjiang Zhou; Baoguo Li; Linshan Zhang; Agata M. Rudolf; Zengguang Jin; Catherine Hambly; Guanlin Wang; John R. Speakman

doi:10.1038/s41467-024-46589-x

Maternal dietary fat during lactation shapes single nucleus transcriptomic profile of postnatal offspring hypothalamus in a sexually dimorphic manner in mice

Yi Huang, Anyongqi Wang, Wenjiang Zhou, Baoguo Li, Linshan Zhang, Agata M. Rudolf, Zengguang Jin, Catherine Hambly, Guanlin Wang^*, John R. Speakman^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Maternal overnutrition during lactation predisposes offspring to develop metabolic diseases and exacerbates the relevant syndromes in males more than females in later life. The hypothalamus is a heterogenous brain region that regulates energy balance. Here we combined metabolic trait quantification of mother and offspring mice under low and high fat diet (HFD) feeding during lactation, with single nucleus transcriptomic profiling of their offspring hypothalamus at peak lacation to understand the cellular and molecular alterations in response to maternal dietary pertubation. We found significant expansion in neuronal subpopulations including histaminergic (Hdc), arginine vasopressin/retinoic acid receptor-related orphan receptor β (Avp/Rorb) and agouti-related peptide/neuropeptide Y (AgRP/Npy) in male offspring when their mothers were fed HFD, and increased Npy-astrocyte interactions in offspring responding to maternal overnutrition. Our study provides a comprehensive offspring hypothalamus map at the peak lactation and reveals how the cellular subpopulations respond to maternal dietary fat in a sex-specific manner during development.

Original language	English
Article number	2382
Number of pages	17
Journal	Nature Communications
Volume	15
DOIs	https://doi.org/10.1038/s41467-024-46589-x
Publication status	Published - 16 Mar 2024

Data Availability Statement

The raw mouse hypothalamus snRNA-seq FASTQ files generated in this study have been deposited in the Gene Expression Omnibus (GEO) database under accession code GSE217677. The reference genome used for raw sequencing reads alignment is mm10-3.0.0. The processed mouse hypothalamus data is also available at GSE217677. Dataset related to HypoMap project used in the study are available at: https://www.repository.cam.ac.uk/items/8f9c3683-29fd-44f3-aad5-7acf5e963a75). An interactive data portal is developed based on the processed dataset and is available online https://mouse10x.shinyapps.io/p15atlas/. All experimental data supporting the findings of this study are available within the paper and its Supplementary Information and Source data are provided with this paper.

Code availability
All scripts used in the current study is available on GitHub (https://github.com/hyhy200g/MouseHypothalamus_snRNA-seq) and on Zenodo (https://doi.org/10.5281/zenodo.10654924)116, the used packages are listed in the Methods

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title = "Maternal dietary fat during lactation shapes single nucleus transcriptomic profile of postnatal offspring hypothalamus in a sexually dimorphic manner in mice",

abstract = "Maternal overnutrition during lactation predisposes offspring to develop metabolic diseases and exacerbates the relevant syndromes in males more than females in later life. The hypothalamus is a heterogenous brain region that regulates energy balance. Here we combined metabolic trait quantification of mother and offspring mice under low and high fat diet (HFD) feeding during lactation, with single nucleus transcriptomic profiling of their offspring hypothalamus at peak lacation to understand the cellular and molecular alterations in response to maternal dietary pertubation. We found significant expansion in neuronal subpopulations including histaminergic (Hdc), arginine vasopressin/retinoic acid receptor-related orphan receptor β (Avp/Rorb) and agouti-related peptide/neuropeptide Y (AgRP/Npy) in male offspring when their mothers were fed HFD, and increased Npy-astrocyte interactions in offspring responding to maternal overnutrition. Our study provides a comprehensive offspring hypothalamus map at the peak lactation and reveals how the cellular subpopulations respond to maternal dietary fat in a sex-specific manner during development.",

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AU - Rudolf, Agata M.

AU - Jin, Zengguang

AU - Hambly, Catherine

AU - Wang, Guanlin

AU - Speakman, John R.

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Maternal dietary fat during lactation shapes single nucleus transcriptomic profile of postnatal offspring hypothalamus in a sexually dimorphic manner in mice

Abstract

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