Fat content in infant mesenchymal stem cells prospectively associates with childhood adiposity and fasting glucose

Abstract

Objective In human studies, new model systems are needed for improved mechanistic investigation of developmental predisposition for metabolic disease but also to serve as benchmarks in early life prevention or intervention efforts. In this regard, human infant umbilical cord–derived mesenchymal stem cells (MSCs) are an emerging tool. However, long‐term clinical relevance to in vivo markers of metabolic disease is unknown. Methods In a cohort of 124 mother/child dyads, this study tested the hypothesis that triglyceride content (TG) of infant MSCs undergoing adipogenesis in vitro (MSC‐TG) is associated with in vivo adiposity (percent fat mass) from birth to early childhood and with fasting glucose and insulin in early childhood. Results MSC‐TG was positively associated with in vivo child adiposity at birth, age 4 to 6 months, and age 4 to 6 years. MSC‐TG was associated with fasting glucose, but not insulin, at 4 to 6 years. Importantly, MSC‐TG explained an additional 13% variance in child adiposity at 4 to 6 years, after accounting for other established birth predictors (weight and percent fat mass at birth) and other established covariates related to child adiposity (e.g., breastfeeding exposure, physical activity). Conclusions This work demonstrates the strength of the MSC model for predicting offspring metabolic phenotype into childhood, even when considering the important contribution of other early life risk factors.

Obesity and Wound Healing: Focus on Mesenchymal Stem Cells

“…Consistent with these findings, an exercise-induced switch in MSC differentiation from adipogenesis to osteogenesis has been proposed as a potential biomarker for monitoring the effects of a healthier lifestyle on diabetes [ 176 ]. The fat content in umbilical cord-derived MSCs has been demonstrated to be an independent predictor of the offspring metabolic phenotype in terms of adiposity and fasting glucose levels [ 177 ]; such results confirm MSC alterations to be possibly involved in the development of obesity-related disorders.…”

Adipocyte hypertrophy in mesenchymal stem cells from infants of mothers with obesity

“…We have reported that fat content of adipocytes derived from umbilical cord MSCs predicts adiposity through 4 to 6 years of age in 70 children, more robustly than birth weight or birth adiposity [19], supporting the clinical relevance of assessing child obesity‐related phenotypes in infant MSCs. However, explicit interrogation of human infant adipocyte size, which may contribute to health outcomes such as inflammation and insulin resistance [20,21], is prohibitively invasive.…”

The role of mesenchymal stem cells in early programming of adipose tissue in the offspring of women with obesity

“…37 Furthermore, recent studies showed that lipid accumulation in Wharton Jelly MSCs correlates to metabolic features in neonates, suggesting that phenotypical characteristics of MSCs do translate to the clinical outcome of the child. 66 This means that early metabolic dysregulations may establish the adipocyte pool and programme longterm effects: this has been associated with adiposity gain 67 (Figure 2).…”