Transferred maternal fatty acids stimulate fetal adipogenesis and lead to neonatal and adult obesity

Abstract

The prevalence of adult and childhood obesity are increasing. Most of the human newborn's body fat accumulates in the last half of intrauterine life. Fat in the fetus was thought to be mostly synthesized from glucose, but now it is commonly accepted that the bulk of it is the product of placental transfer of maternal fatty acids. Transported fatty acids originate in maternal plasma "free" fatty acids, fatty acids hydrolyzed from maternal plasma triglycerides, and the poly-unsaturated fatty acid component of maternal phospholipids. Glucose remains an important precursor of alpha-glycerol phosphate, to which most transported fatty acids are eventually esterified. Maternal plasma lipids are elevated in late pregnancy and even more in obese and diabetic pregnant women. This accelerates the placental transport of fatty acids. The hypothesis presented in this paper rests on the observations that the exponential increase in fat tissue in the human embryo's body occurs in time to parallel the increase of lipids in the mother's blood and depends on the chemical affinity of the transcription factor PPAR gamma to fatty acids and on fatty acid stimulation of adipocyte generation from precursor cells. The hypothesis asserts that transported maternal fatty acids activate the transcription factors in the fetus and initiate conversion of the mesenchymal stem cells into adipocytes. In obese and diabetic mothers, the higher plasma lipids facilitate increased placental fatty acid transfer. This will increase adipocyte generation and, through this, the prevalence of babies with increased fat cell size and number. Babies born with increased adipose tissue cellularity will have greater probability of growing up to become obese adolescents and adults. These newborns, whose obesity is hyperplastic as well as hypertrophic, as adults will have difficulty losing weight through diet and exercise or will regain the lost weight more quickly than others without these characteristics. Accordingly, increased placental fatty acid transfer and accelerated adipocyte generation may explain not only neonatal obesity, but some aspects of the adult obesity epidemic also. It is therefore recommended that prevention of fetal fat cell hyperplasia, by lowering maternal plasma lipids in mid and late pregnancy, should be attempted in pregnancies at risk for macrosomia.