Gene coexpression network analysis reveals perirenal adipose tissue as an important target of prenatal malnutrition in sheep

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We have previously demonstrated that pre-and early postnatal malnutrition in sheep induced depot-and sex-specific changes in adipose morphological features, metabolic outcomes, and transcriptome in adulthood, with perirenal (PER) as the major target followed by subcutaneous (SUB) adipose tissue. We aimed to identify coexpressed and hub genes in SUB and PER to identify the underlying molecular mechanisms contributing to the early nutritional programming of adipose-related phenotypic outcomes. Transcriptomes of SUB and PER of male and female adult sheep with different pre-and early postnatal nutrition histories were used to construct networks of coexpressed genes likely to be functionally associated with pre-and early postnatal nutrition histories and phenotypic traits using weighted gene coexpression network analysis. The modules from PER showed enrichment of cell cycle regulation, gene expression, transmembrane transport, and metabolic processes associated with both sexes’ prenatal nutrition. In SUB (only males), a module of enriched adenosine diphosphate metabolism and development correlated with prenatal nutrition. Sex-specific module enrichments were found in PER, such as chromatin modification in the male network but his-tone modification and mitochondria-and oxidative phosphorylation-related functions in the female network. These sex-specific modules correlated with prenatal nutrition and adipocyte size distribution patterns. Our results point to PER as a primary target of prenatal malnutrition compared to SUB, which played only a minor role. The prenatal programming of gene expression and cell cycle, potentially through epigenetic modifications, might be underlying mechanisms responsible for observed changes in PER expandability and adipocyte-size distribution patterns in adulthood in both sexes.

OriginalsprogEngelsk
TidsskriftPhysiological Genomics
Vol/bind55
Udgave nummer9
Sider (fra-til)392-413
Antal sider22
ISSN1094-8341
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This study was part of the research program of the Center for Foetal Programming (CFP), Denmark, and animal experiments were funded by the Danish Council for Strategic Research, Denmark (Grant 09067124). The Ministry of Higher Education, Malaysia, funded the RNA-sequencing analyses. The Ministry of Higher Education, Malaysia, and the Universiti Putra Malaysia sponsored the main authors’ Ph.D. scholarship.

Publisher Copyright:
© 2023 The Authors.

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