Maternal gestational diabetes mellitus modulates adipose tissue remodeling and CTRP6 expression in a depot- and sex-specific manner in mouse offspring

Objective This study aimed to explore how maternal gestational diabetes mellitus (GDM) affects adipose tissue remodeling and the expression of C1q/TNF-related protein 6 (CTRP6) in offspring, with a focus on sex- and depot-specific differences. Methods A GDM mouse model was established by feeding female C57BL/6J mice a high-fat diet (HFD) before and during pregnancy. Offspring were weaned onto standard chow or HFD until 9 weeks of age. Metabolic phenotypes, adipose tissue morphology, and CTRP6 expression were assessed at weaning and adulthood. Results GDM offspring exhibited increased adiposity and impaired glucose tolerance at weaning, with these effects persisting into adulthood in males. Maternal GDM reduced plasma CTRP6 levels in both sexes at weaning, but in adulthood, male GDM offspring maintained lower circulating CTRP6, while females on chow diet showed elevated levels. Tissue-specific analysis revealed decreased CTRP6 expression in male interscapular brown adipose tissue (iBAT) and female visceral white adipose tissue (vWAT), accompanied by depot- and sex-specific changes in adiponectin signaling. Conclusion Maternal GDM programs offspring’s metabolic phenotype and adipose tissue CTRP6 expression in a sex- and depot-specific manner, suggesting CTRP6 may be a key mediator in the intergenerational transmission of metabolic disease risk.