Early origins of obesity: programming the appetite regulatory system

Abstract

There is evidence that changes in perinatal nutrition programme the development of relative fat mass and the regulation of appetite in adult life. These studies have been primarily in the rodent utilizing maternal overnutrition or undernutrition imposed at different stages of pregnancy and beyond, mapping of neuropeptide localization and activity and appropriate null mutant models. Whilst the rodent offers significant advantages in terms of a short gestation and the availability of useful transgenic and null mutant models, there are also advantages to using an animal model more akin to the human, in which all components of the 'fat-brain axis' are present before birth, such as the sheep. This review summarizes recent work on the expression and localization of the 'appetite regulatory' peptides in the fetal rodent and sheep hypothalamus and their potential role in the early programming of postnatal appetite and obesity.

Figure 1. Autoradiographic images of coronal sections through fetal sheep hypothalamus at 110 days gestation (term ≈ 147 days) showing gene expression for NPY, AgRP, POMC, CART and leptin receptor (OB-Rb)

3V, third ventricle; ARC, arcuate nucleus; ME, median eminence; VMH, ventromedial hypothalamus; DMH, dorsomedial hypothalamus; PVN, paraventricular nucleus; R, reuniens thalamic nucleus; OC, optic chiasm. Scale bar = 1.5 mm. (From Mühlhäusler et al. 2004, with permission from Blackwell Publishing Ltd.)