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 - Salleh, Suraya Mohamad

AU - Cai, Zexi

AU - Nielsen, Mette Olaf

N1 - Publisher Copyright: © 2023 The Authors.

PY - 2023

Y1 - 2023

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 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.

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 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.

KW - early postnatal malnutrition

KW - perirenal adipose tissue

KW - prenatal malnutrition

KW - subcutaneous adipose tissue

KW - WGCNA

U2 - 10.1152/physiolgenomics.00128.2022

DO - 10.1152/physiolgenomics.00128.2022

M3 - Journal article

C2 - 37458462

AN - SCOPUS:85169419179

VL - 55

SP - 392

EP - 413

JO - Physiological Genomics

JF - Physiological Genomics

SN - 1094-8341

IS - 9

ER -