# Maternal Gestational Diabetes Mellitus Modulates Adipose Tissue Remodeling and CTRP6 Expression in a Depot- and Sex-Specific Manner in Mouse Offspring

## TL;DR

Maternal gestational diabetes affects fat tissue and a protein called CTRP6 in offspring, with differences based on sex and fat location.

## Contribution

The study reveals sex- and depot-specific effects of maternal GDM on adipose tissue remodeling and CTRP6 expression in offspring.

## Key findings

- GDM offspring showed increased adiposity and impaired glucose tolerance at weaning.
- Maternal GDM reduced plasma CTRP6 in offspring, with sex-specific persistence into adulthood.
- CTRP6 expression and adiponectin signaling changed in a depot- and sex-specific manner.

## Abstract

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 an 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 the 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. Conclusions: Maternal GDM programs offspring’s metabolic phenotype and adipose tissue CTRP6 expression in a sex- and depot-specific manner, suggesting CTRP6 may serve as an early, sex-biased indicator of the intergenerational transmission of metabolic disease risk.