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

Sharmila Ahmad; Markus Hodal Drag; Suraya Mohamad Salleh; Zexi Cai; Mette Olaf Nielsen

doi:10.1152/physiolgenomics.00128.2022

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

Sharmila Ahmad^*, Markus Hodal Drag, Suraya Mohamad Salleh, Zexi Cai, Mette Olaf Nielsen

^*Corresponding author for this work

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Abstract

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.

Original language	English
Journal	Physiological Genomics
Volume	55
Issue	9
Pages (from-to)	392-413
Number of pages	22
ISSN	1094-8341
DOIs	https://doi.org/10.1152/physiolgenomics.00128.2022
Publication status	Published - Sept 2023

Keywords

Adipose Tissue/metabolism
Adiposity
Animals
Female
Male
Malnutrition/genetics
Obesity/genetics
Pregnancy
Sheep
Subcutaneous Fat/metabolism

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

abstract = "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.",

keywords = "Adipose Tissue/metabolism, Adiposity, Animals, Female, Male, Malnutrition/genetics, Obesity/genetics, Pregnancy, Sheep, Subcutaneous Fat/metabolism",

author = "Sharmila Ahmad and Drag, {Markus Hodal} and {Mohamad Salleh}, Suraya and Zexi Cai and Nielsen, {Mette Olaf}",

year = "2023",

month = sep,

doi = "10.1152/physiolgenomics.00128.2022",

language = "English",

volume = "55",

pages = "392--413",

journal = "Physiological Genomics",

issn = "1094-8341",

publisher = "American Physiological Society",

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Gene coexpression network analysis reveals perirenal adipose tissue as an important target of prenatal malnutrition in sheep. / Ahmad, Sharmila; Drag, Markus Hodal; Mohamad Salleh, Suraya et al.
In: Physiological Genomics, Vol. 55, No. 9, 09.2023, p. 392-413.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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

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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 -

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

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