Increased Adipogenic Mesenchymal Stem Cell Programming Mediated by Impaired Wnt Signaling Due to Maternal Obesity, Cesarean Delivery and Infant Formula Feeding: The Perinatal March Toward Obesity

The perinatal period has emerged as a critical window for the development of overweight and obesity and has therefore become a focus of scientific interest. According to the concept of developmental origins of health and disease (DOHaD), the first 1000 days after conception are of critical importance for the proper programming of stem cells. Multipotent mesenchymal stem cells (MSCs) have the capacity to differentiate into adipocytes both prenatally and postnatally. The aim of this review is to provide translational evidence for increased adipogenic programming of MSCs due to maternal obesity, cesarean delivery, and infant formula feeding. All three perinatal exposures plausibly converge on impaired canonical Wnt/β-catenin signaling in MSCs; this is directly supported for maternal obesity and indirectly for cesarean delivery and formula feeding through gut–endocrine mechanisms. Deficient Wnt/β-catenin signaling plays a pivotal role for the early committment of MSCs to the adipocyte lineage. These insights open up a comprehensive new approach to the understanding of the perinatal sequence of molecular events promoting early obesity development. Common medical practices during the perinatal period require reconsideration for the primary prevention of obesity.