Obesity (Silver Spring, Md.) · 2025
Sex-Specific Subcutaneous Adipose Tissue Transcriptome in Obesity: Insights From Monozygotic Twin Pairs Discordant for BMI.
СтатьяTwin StudyНазвание и аннотация: Перевод пока не подготовлен
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Haltia Hanna, Muniandy Maheswary, Heinonen Sini, Saari Sina, Alvarez Marcus, Hakkarainen Antti, Lundbom Jesper, Kuula Juho, Groop Per-Henrik, Kaprio Jaakko, Pajukanta Päivi, Pietiläinen Kirsi H, van der Kolk Birgitta W
Аннотация
OBJECTIVE: We investigated the impact of sex on the subcutaneous adipose tissue (AT) transcriptome and its obesity-related adaptations.
METHODS: We studied rare BMI-discordant monozygotic twin pairs (ΔBMI > 2.5 kg/m2; 21 female, 16 male pairs) to assess how sex affects AT and whole-body metabolism. AT RNA sequencing was analyzed using linear mixed modeling and pathway enrichment for: (1) sex differences in individual twins, adjusted for BMI, (2) sex-stratified effects of acquired obesity (ΔBMI between co-twins separately in females and males), (3) sex-specific effects of obesity (differences in the ΔBMI effect between sexes).
RESULTS: (1) AT transcriptional profiles differed between sexes, associating with insulin sensitivity. (2) Sex-stratified obesity effects within pairs were stronger in females, with upregulated inflammation and downregulated mitochondrial oxidative phosphorylation; males showed increased inflammation and decreased histone modification. (3) The response to obesity was sex-specific: lower expression of genes in unsaturated fatty acid metabolism in obesity was seen in females only. Sex-specific obesity AT gene expression was associated with metabolic health, with a negative association between unsaturated fatty acid metabolism and insulin sensitivity in males only.
CONCLUSIONS: Biological sex influences the AT transcriptome and its response to obesity, highlighting distinct molecular mechanisms that may contribute to sex-specific metabolic health.
METHODS: We studied rare BMI-discordant monozygotic twin pairs (ΔBMI > 2.5 kg/m2; 21 female, 16 male pairs) to assess how sex affects AT and whole-body metabolism. AT RNA sequencing was analyzed using linear mixed modeling and pathway enrichment for: (1) sex differences in individual twins, adjusted for BMI, (2) sex-stratified effects of acquired obesity (ΔBMI between co-twins separately in females and males), (3) sex-specific effects of obesity (differences in the ΔBMI effect between sexes).
RESULTS: (1) AT transcriptional profiles differed between sexes, associating with insulin sensitivity. (2) Sex-stratified obesity effects within pairs were stronger in females, with upregulated inflammation and downregulated mitochondrial oxidative phosphorylation; males showed increased inflammation and decreased histone modification. (3) The response to obesity was sex-specific: lower expression of genes in unsaturated fatty acid metabolism in obesity was seen in females only. Sex-specific obesity AT gene expression was associated with metabolic health, with a negative association between unsaturated fatty acid metabolism and insulin sensitivity in males only.
CONCLUSIONS: Biological sex influences the AT transcriptome and its response to obesity, highlighting distinct molecular mechanisms that may contribute to sex-specific metabolic health.