FETAL FAT, LEPTIN AND THE PROGRAMMING OF ADULT OBESITY

I.C. McMillen, B.S. Yuen, B.S. Muhlhausler, P.C. Owens, Departments of Physiology and Obstetrics and Gynaecology, University of Adelaide, Adelaide, SA 5005.

People who were small at birth tend to have a more abdominal distribution of obesity and a high body fat content in adult life despite a lower BMI. Whilst growth restriction before birth is associated with increased adult adiposity, increased fetal nutrient supply is also associated with the development of obesity in later life. In this context, there has been considerable recent interest in the potential role of the hormone leptin in the early onset of adult obesity. Leptin, a polypeptide hormone, is synthesised and secreted principally by adipocytes and acts in the adult as a circulating signal of fat mass. Leptin binds to specific receptors to decrease food intake and increase energy utilisation thereby maintaining energy balance homeostasis. Serum leptin concentrations are elevated early in the development of childhood-onset obesity and obese children have a high serum leptin even when normalised to fat mass. There have been relatively few experimental studies, however, on the specific impact of alterations in fetal nutrient supply on the synthesis, secretion and actions of leptin before and after birth. We have recently demonstrated that circulating leptin concentrations are positively related to leptin mRNA expression in fetal adipose tissue in fetal sheep during late gestation and that there is a significant relationship between fetal adiposity, adipocyte cell size and circulating leptin concentrations in fetal sheep of ewes fed at or above maintenance energy requirements. We have also demonstrated that leptin infusion into fetal sheep in late gestation results in changes in the structural and functional characteristics of fetal fat. Thus leptin can act as a signal of adiposity in fetal life and alterations in the synthesis, secretion or actions of leptin may therefore play an important role in the early programming of adult obesity.