Increased maternal nutrition alters development of the appetite‐regulating network in the brain

Abstract

Individuals exposed to an increased nutrient supply before birth have a high risk of becoming obese children and adults. It has been proposed that exposure of the fetus to high maternal nutrient intake results in permanent changes within the central appetite regulatory network. No studies, however, have investigated the impact of increased maternal nutrition on the appetite regulatory network in species in which this network develops before birth, as in the human. In the present study, pregnant ewes were fed a diet which provided 100% (control, n = 8) or approximately 160% (well-fed, n = 8) of metabolizable energy requirements. Ewes were allowed to lamb spontaneously, and lambs were sacrificed at 30 days of postnatal age. All fat depots were dissected and weighed, and expression of the appetite-regulating neuropeptides and the leptin receptor (OBRb) were determined by in situ hybridization. Lambs of well-fed ewes had higher glucose (Glc) concentrations during early postnatal life (F = 5.93, P<0.01) and a higher relative subcutaneous (s.c.) fat mass at 30 days of age (34.9+/-4.7 g/kg vs. 22.8+/-3.3 g/kg; P<0.05). The hypothalamic expression of pro-opiomelanocortin was higher in lambs of well-fed ewes (0.48+/-0.09 vs. 0.28+/-0.04, P<0.05). In lambs of overnourished mothers, but not in controls, the expression of OBRb was inversely related to total relative fat mass (r2 = 0.50, P = 0.05, n = 8), and the direct relationship between the expression of the central appetite inhibitor CART and fat mass was lost. The expression of neuropeptide Y and AGRP was inversely related to total relative fat mass (NPY, r2 = 0.28, P<0.05; agouti-related peptide, r2 = 0.39, P<0.01). These findings suggest that exposure to increased nutrition before birth alters the responses of the central appetite regulatory system to signals of increased adiposity after birth.

Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor

“…Maternal nutrition during pregnancy has previously been shown to program the appetite-regulation in the offspring (21,46,47,59), which is proposed to involve leptin. Leptin, an adipocyte-derived hormone has been reported to influence the appetite-controlling centers in the brain and hence is proposed to play an important role in the regulation of food intake (47,58). A diet rich in SFA has been reported to increase plasma leptin concentrations both in mice as well as in humans (15,23).…”

Epigenetics and developmental programming of welfare and production traits in farm animals

“…The magnitude and direction of the effect observed is dependent on the age of the offspring and the timing of the nutritional insult during gestation. In relatively young (late fetal or early neonatal) offspring (up to ,77 days of gestation), adiposity tends to go in the direction you would expect, with reduced nutrition resulting in reduced adiposity and vice versa (Muhlhausler et al 2006;Luther et al 2007). After the neonatal period, and up to and including the period when lambs in the UK reach normal 'market weight' (i.e.…”

Developmental and epigenetic pathways to obesity: an evolutionary-developmental perspective

“…94 These appetite control circuits are plastic in early life and can be affected by nutritional factors, although the critical windows for plasticity are dependent on the maturity at birth of the particular species. Maternal or fetal hyperglycemia, maternal overfeeding during pregnancy or postnatal overfeeding of the offspring have been shown to affect the maturation and functioning of these appetite-controlling hypothalamic networks, both in the sheep where (as in humans) the regulatory circuits are relatively mature at birth 95 and in the rat where the circuits are not fully developed until shortly before weaning. 96 The critical window for hypernutrition may extend further into postnatal life, as numerous clinical studies, summarized in systematic reviews and meta-analyses, 33,[97][98][99] have shown that rapid weight gain during early infancy is associated with susceptibility to obesity in adulthood.…”