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

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. W...

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Veröffentlicht in:Physiological genomics 2023-07
Hauptverfasser: Ahmad, Sharmila, Drag, Markus Hodal, Salleh, Suraya Mohamad, Cai, Zexi, Nielsen, Mette Olaf
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creator Ahmad, Sharmila
Drag, Markus Hodal
Salleh, Suraya Mohamad
Cai, Zexi
Nielsen, Mette Olaf
description 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 co-expressed 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 co-expressed genes likely to be functionally associated with pre-and early postnatal nutrition histories, and phenotypic traits using Weighted Gene Co-expression 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 histone 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.
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We aimed to identify co-expressed 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 co-expressed genes likely to be functionally associated with pre-and early postnatal nutrition histories, and phenotypic traits using Weighted Gene Co-expression 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. 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title Gene co-expression network analysis reveals perirenal adipose tissue as an important target of prenatal malnutrition in sheep
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