Obesity induced transcriptional changes in skeletal muscle across different species.

Pigs on high-fat diets maintaining metabolic homeostasis and are resistant to hepatic steatosis, differing from humans and mice. Obesity-induced metabolic dysregulation and inflammation in skeletal muscle are well-studied in humans and mice, but less is known about pig skeletal muscle responses. Thi...

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Main Authors: Yujie Wang, Jiaman Zhang, Xintong Yang, Fuwen Wang, Long Jin, Jing Li, Xuewei Li, Mingzhou Li
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0327988
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author Yujie Wang
Jiaman Zhang
Xintong Yang
Fuwen Wang
Long Jin
Jing Li
Xuewei Li
Mingzhou Li
author_facet Yujie Wang
Jiaman Zhang
Xintong Yang
Fuwen Wang
Long Jin
Jing Li
Xuewei Li
Mingzhou Li
author_sort Yujie Wang
collection DOAJ
description Pigs on high-fat diets maintaining metabolic homeostasis and are resistant to hepatic steatosis, differing from humans and mice. Obesity-induced metabolic dysregulation and inflammation in skeletal muscle are well-studied in humans and mice, but less is known about pig skeletal muscle responses. This study constructs the skeletal muscle transcriptome of obese pigs and integrates it with publicly available transcriptional profiles from obese humans and mice, and ATAC-seq data from lean individuals across species. We systematically characterized transcriptional changes in skeletal muscle under stress of obesity, focusing on the evolution of gene families, orthologous genes, and epigenetic regulation. Our results show that obesity activates lipid catabolism genes and inhibits immune response genes in pig skeletal muscle, contrasting with humans and mice. We identify expanding gene families in pigs, such as olfactory receptors, α-amylase, and ABC transporters, which are upregulated in obesity. While oxidative metabolism-related gene families are contracted in the human and mouse genomes and are downregulated with obesity. By comparing orthologous genes, we identify a set of divergently changing genes induced by obesity across species, which primarily participate in lipid metabolism, inflammation, and immune cell activation. High-divergence genes show conserved coding and promoter sequences, and exhibit greater chromatin accessibility in promoter regions, compare with low-divergence genes. These findings suggest that gene dosage and transcriptional plasticity contribute to species-specific expression divergent responses to obesity. Identifying rapidly evolving gene families, divergently expressed genes, and potential transcription factor binding sites may reveal new insights into obesity-related metabolic disorders and therapeutic targets.
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spelling doaj-art-941ebf6fdff54b678734e6e466eb752e2025-08-20T03:27:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01207e032798810.1371/journal.pone.0327988Obesity induced transcriptional changes in skeletal muscle across different species.Yujie WangJiaman ZhangXintong YangFuwen WangLong JinJing LiXuewei LiMingzhou LiPigs on high-fat diets maintaining metabolic homeostasis and are resistant to hepatic steatosis, differing from humans and mice. Obesity-induced metabolic dysregulation and inflammation in skeletal muscle are well-studied in humans and mice, but less is known about pig skeletal muscle responses. This study constructs the skeletal muscle transcriptome of obese pigs and integrates it with publicly available transcriptional profiles from obese humans and mice, and ATAC-seq data from lean individuals across species. We systematically characterized transcriptional changes in skeletal muscle under stress of obesity, focusing on the evolution of gene families, orthologous genes, and epigenetic regulation. Our results show that obesity activates lipid catabolism genes and inhibits immune response genes in pig skeletal muscle, contrasting with humans and mice. We identify expanding gene families in pigs, such as olfactory receptors, α-amylase, and ABC transporters, which are upregulated in obesity. While oxidative metabolism-related gene families are contracted in the human and mouse genomes and are downregulated with obesity. By comparing orthologous genes, we identify a set of divergently changing genes induced by obesity across species, which primarily participate in lipid metabolism, inflammation, and immune cell activation. High-divergence genes show conserved coding and promoter sequences, and exhibit greater chromatin accessibility in promoter regions, compare with low-divergence genes. These findings suggest that gene dosage and transcriptional plasticity contribute to species-specific expression divergent responses to obesity. Identifying rapidly evolving gene families, divergently expressed genes, and potential transcription factor binding sites may reveal new insights into obesity-related metabolic disorders and therapeutic targets.https://doi.org/10.1371/journal.pone.0327988
spellingShingle Yujie Wang
Jiaman Zhang
Xintong Yang
Fuwen Wang
Long Jin
Jing Li
Xuewei Li
Mingzhou Li
Obesity induced transcriptional changes in skeletal muscle across different species.
PLoS ONE
title Obesity induced transcriptional changes in skeletal muscle across different species.
title_full Obesity induced transcriptional changes in skeletal muscle across different species.
title_fullStr Obesity induced transcriptional changes in skeletal muscle across different species.
title_full_unstemmed Obesity induced transcriptional changes in skeletal muscle across different species.
title_short Obesity induced transcriptional changes in skeletal muscle across different species.
title_sort obesity induced transcriptional changes in skeletal muscle across different species
url https://doi.org/10.1371/journal.pone.0327988
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AT jiamanzhang obesityinducedtranscriptionalchangesinskeletalmuscleacrossdifferentspecies
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AT fuwenwang obesityinducedtranscriptionalchangesinskeletalmuscleacrossdifferentspecies
AT longjin obesityinducedtranscriptionalchangesinskeletalmuscleacrossdifferentspecies
AT jingli obesityinducedtranscriptionalchangesinskeletalmuscleacrossdifferentspecies
AT xueweili obesityinducedtranscriptionalchangesinskeletalmuscleacrossdifferentspecies
AT mingzhouli obesityinducedtranscriptionalchangesinskeletalmuscleacrossdifferentspecies