Figure 3. Proposed model of mechanistic links between maternal obesity, fetal overgrowth/increased infant adiposity and fetal programming of adult disease.

We propose that the mechanistic link between maternal obesity, fetal overgrowth/increased infant adiposity and programming of adult disease involves specific changes in the placenta from increased mTOR signaling. High insulin, leptin, IGF-1 and nutrient levels and low adiponectin in the maternal circulation are key examples of factors that converge to activate placental mTOR signalling, a positive regulator of an array of key placental functions, including amino acid transport and mitochondrial biogenesis. Some of the proposed involved signaling mechanisms are depicted in more detail in Figure 2. These changes are proposed to promote the delivery of nutrients (which may include glucose, amino acids and lipids) to the fetus, increased fetal growth and/or adiposity, which are strongly linked to the development of metabolic and cardiovascular disease in childhood and adult life. IGF-1, insulin-like growth factor 1; mTOR, mechanistic target of rapamycin.