PLACENTAL FREE-FATTY-ACID TRANSFER AND FETAL ADIPOSE-TISSUE DEVELOPMENT: AN EXPLANATION OF FETAL ADIPOSITY IN INFANTS OF DIABETIC MOTHERS

Abstract

A new hypothesis on adipose-tissue development during intrauterine life is presented. It is proposed that circulating maternal plasma free fatty acids (F.F.A.) are the major precursors of triglyceride fatty acids in the fetal adipose tissue. Maternal F.F.A. is transported across the placenta and is carried in the blood of the fetus to the developing fat cells. After being taken up by the adipocytes, F.F.A. is esterified and is incorporated into the adipose-tissue triglyceride pool. Since diabetics have higher plasma-F.F.A. levels than non-diabetic pregnant women, the gradient-dependent diffusion type of transfer of F.F.A. across the placenta is faster in these cases. This results in increased availability in fetal plasma of F.F.A. to be taken up by the adipocytes. It is suggested that glucose is not the major precursor of triglyceride fatty acids—as it was thought to be in the past—but serves as the primary substrate for α-glycerophosphate production. As α-glycerophosphate is necessary for the esterification of F.F.A., hyperglycæmia and hyper-insulinæmia in fetuses of diabetic mothers may facilitate the esterification process in the fetal adipocytes. This hypothesis assigns a major role to maternal plasma F.F.A. but only a minor role to blood-sugar levels in the pathogenesis of fetal adiposity in infants of diabetic mothers. The hypothesis is therefore compatible with the paradoxical finding that, despite their normal (or near normal) blood-sugar levels, prediabetic women often give birth to obese " diabetic-type " babies, while overtly hyperglycæmic diabetic mothers may have normal or even small newborns.