Abstract
The intrauterine period is a critical time wherein developmental exposure can influence risk for chronic disease including childhood obesity. Using umbilical cord-derived mesenchymal stem cells (uMSC) from offspring born to normal-weight and obese mothers, we tested the hypothesis that changes in infant body composition over the first 5 months of life correspond with differences in cellular metabolism and transcriptomic profiles at birth. Higher long-chain acylcarnitine concentrations, lipid transport gene expression, and indicators of oxidative stress in uMSC-adipocytes were related to higher adiposity at 5 months of age. In uMSC-myocytes, lower amino acid concentrations and global differential gene expression for myocyte growth, amino acid biosynthesis, and oxidative stress were related to lower infant percent fat-free mass at 5 months of age, particularly in offspring of obese mothers. This is the first evidence of human infant adipocyte- or myocyte-related alterations in cellular metabolic pathways that correspond with increased adiposity and lower fat-free mass in early infancy. These pathways might reflect the effects of an adverse maternal metabolic environment on the fetal metabolome and genome. Our findings suggest that programmed differences in infant stem cell metabolism correspond with differences in body composition in early life, a known contributor to obesity risk.
Highlights
Intrauterine development is a period of rapid growth and tissue remodeling, during which the fetus is vulnerable to conditions that adversely impact organ development and disease propensity later in life
Relative to the mean %FM and %FFM in our experimental sample, there was a clear separation of offspring with higher 5 month-adiposity and higher postnatal gain in adiposity (RPG; higher %FM and lower %FFM at 5 months compared to the mean; n = 10) versus infants with lower postnatal gain in adiposity (LPG; lower %FM and higher %FFM at 5 months compared to the mean; n = 13)
No differences were observed between the rapid postnatal gain (RPG) and LPG groups in maternal pre-pregnancy BMI (ppBMI), gestational weight gain, maternal metabolic markers in the 2nd trimester, birth weight, infant gender, or exclusive breastfeeding (Table 1)
Summary
Infant phenotypic analysis reveals two distinct groups characterized by adiposity at 5 months of life. We investigated the differences in long-chain acylcarnitines and lipid transport-related gene expression between RPG vs LPG by maternal ppBMI status, and in OB-only and NW-only groups. Acylcarnitine analysis for uMSC-adipocytes revealed higher concentrations of the long-chain acylcarnitines C18 (P = 0.001), C16 (P = 0.03), C18:1 (P = 0.023), and the ratio C0/(C16 + C18) (P = 0.022) in the RPG vs LPG group (Fig. 2a; Supplemental Table 2). No other differentially regulated genes in fatty acid oxidation were noted, nor was there evidence of pathway enrichment by analysis of global differential gene expression, in uMSC-adipocytes Together, these results support upregulated transport of fatty acids across the cell membrane, functional coupling for mitochondrial transport by CPT1 (to create long-chain acylcarnitines), and incomplete beta-oxidation in the RPG group compared with the LPG group, in RPG offspring of OB mothers
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
