TY - JOUR
T1 - Gene coexpression network analysis reveals perirenal adipose tissue as an important target of prenatal malnutrition in sheep
AU - Ahmad, Sharmila
AU - Drag, Markus Hodal
AU - Mohamad Salleh, Suraya
AU - Cai, Zexi
AU - Nielsen, Mette Olaf
PY - 2023/9
Y1 - 2023/9
N2 - 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 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.
AB - 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 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.
KW - Adipose Tissue/metabolism
KW - Adiposity
KW - Animals
KW - Female
KW - Male
KW - Malnutrition/genetics
KW - Obesity/genetics
KW - Pregnancy
KW - Sheep
KW - Subcutaneous Fat/metabolism
UR - http://www.scopus.com/inward/record.url?scp=85169419179&partnerID=8YFLogxK
U2 - 10.1152/physiolgenomics.00128.2022
DO - 10.1152/physiolgenomics.00128.2022
M3 - Journal article
C2 - 37458462
SN - 1094-8341
VL - 55
SP - 392
EP - 413
JO - Physiological Genomics
JF - Physiological Genomics
IS - 9
ER -