Prenatal programming of postnatal obesity: fetal nutrition and the regulation of leptin synthesis and secretion before birth.
Exposure to either an increased or decreased level of intrauterine nutrition can result in an increase in adiposity and in circulating leptin concentrations in later life. In animals such as the sheep and pig in which fat is deposited before birth, leptin is synthesised in fetal adipose tissue and is present in the fetal circulation throughout late gestation. In the sheep a moderate increase or decrease in the level of maternal nutrition does not alter fetal plasma leptin concentrations, but there is evidence that chronic fetal hyperglycaemia and hyperinsulinaemia increase fetal fat mass and leptin synthesis within fetal fat depots. Importantly, there is a positive relationship between the relative mass of the 'unilocular' component of fetal perirenal and interscapular adipose tissue and circulating fetal leptin concentrations in the sheep. Thus, as in the neonate and adult, circulating leptin concentrations may be a signal of fat mass in fetal life. There is also evidence that leptin can act to regulate the lipid storage, leptin synthetic capacity and potential thermogenic functions of fat before birth. Thus, leptin may act as a signal of energy supply and have a 'lipostatic' role before birth. Future studies are clearly required to determine whether the intrauterine and early postnatal nutrient environment programme the endocrine feedback loop between adipose tissue and the central and peripheral neuroendocrine systems that regulate energy balance, resulting in an enhanced risk of obesity in adult life.
McMillen
I C
IC
Discipline of Physiology, School of Molecular and Biomedical Sciences, University of Adelaide, SA 5005, Australia. caroline.mcmillen@adelaide.edu.au
Muhlhausler
B S
BS
Duffield
J A
JA
Yuen
B S J
BS
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001724:Birth Weight / Q000502:physiology*; D005314:Embryonic and Fetal Development / Q000502:physiology*; D004734:Energy Metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D020738:Leptin / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D009752:Nutritional Status; D009765:Obesity / Q000453:epidemiology / Q000209:etiology; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena / Q000502:physiology*; D012756:Sheep; D013552:Swine
D020738:Leptin