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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: 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.

SUBMITTER: Huang Y

PROVIDER: S-EPMC10944494 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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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.

Huang Yi Y Wang Anyongqi A Zhou Wenjiang W Li Baoguo B Zhang Linshan L Rudolf Agata M AM Jin Zengguang Z Hambly Catherine C Wang Guanlin G Speakman John R JR

Nature communications 20240316 1

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 ...[more]

PMID: 38493217

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Project description:To identify genes that are downstream of gonadal hormones and that control dimorphic behaviors, we used a MEEBO array platform to profile gene expression of adult male and female hypothalamus against a whole brain reference sample. The experimental design allowed us to identify genes that are upreguated in the hypothalamus compared to the whole brain and are dimorphically expressed between the two sexes. In situ hybridization of candiate genes were carried out to validate the dimorphic expression of these genes in the hypothalamus. Array results were used to create a list of genes to screen by in situ hybridization. For each normalization method, a list of genes that were upregulated in the male or the female was created, and a gene had to be on a set number of these individual normalization lists in order to be considered for screening. A similar method was used to create a list of hypothalamic upregulated genes. The final screening list was comprised of genes that were upregulated in the male or female as well as in the hypothalamus. If in situ hybridization proved that the gene was upregulated in the male or female brain, we concluded that that transcript was differentially expressed. No one normalization method was weighted over another, and the array results were used to create a screening list for in situ hybridizations. Hypothalami from 4 adult animals of each sex were microdissected and pooled for each experimental sample and the whole brain plus pituitary from one male and one female were pooled to provide the reference sample. Each set of samples (male and female) was hybridized to two arrays to provide two technical replicates for each set of samples taken. A total of three sets of samples were taken (three biological replicates). For the "_amp" Samples, source (hypothalamus and whole brain) mRNA was amplified using T7 based method. For this set, data were not normalized, rather the raw intensities were used to calculate ratios. Candidate genes from this study was also included in final list in situ screening.

Dataset Information

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

Publications

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

Similar Datasets

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