title: Developmental programming of hypothalamic neuronal circuits: impact on energy balance control.
abstract: The prevalence of obesity in adults and children has increased globally at an alarming rate. Mounting evidence from both epidemiological studies and animal models indicates that adult obesity and associated metabolic disorders can be programmed by intrauterine and early postnatal environment- a phenomenon known as "fetal programming of adult disease." Data from nutritional intervention studies in animals including maternal under- and over-nutrition support the developmental origins of obesity and metabolic syndrome. The hypothalamic neuronal circuits located in the arcuate nucleus controlling appetite and energy expenditure are set early in life and are perturbed by maternal nutritional insults. In this review, we focus on the effects of maternal nutrition in programming permanent changes in these hypothalamic circuits, with experimental evidence from animal models of maternal under- and over-nutrition. We discuss the epigenetic modifications which regulate hypothalamic gene expression as potential molecular mechanisms linking maternal diet during pregnancy to the offspring's risk of obesity at a later age. Understanding these mechanisms in key metabolic genes may provide insights into the development of preventative intervention strategies.
authors.affiliation: Faculty of Life Sciences, University of Manchester Manchester, UK.
authors.forename: Thanuja
authors.initials: T
authors.lastname: Gali Ramamoorthy
authors.affiliation: School of Clinical and Experimental Medicine, University of Birmingham Birmingham, UK.
authors.forename: Ghazala
authors.initials: G
authors.lastname: Begum
authors.affiliation: Faculty of Life Sciences, University of Manchester Manchester, UK.
authors.forename: Erika
authors.initials: E
authors.lastname: Harno
authors.affiliation: Faculty of Life Sciences, University of Manchester Manchester, UK ; Faculty of Medical and Human Sciences, Centre for Endocrinology and Diabetes, University of Manchester Manchester, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: White
keywords: epigenetics; fetal programming; glucocorticoid receptor; hypothalamus; pro-opiomelanocortin