Introduction

The perinatal environment exerts profound effects on the structure andfunction of the mammalian central nervous system (CNS). Although certainexperiences are essential for orderly brain development to proceed, theoccurrence of some harmful experiences can also have deleteriousconsequences on the developing brain. Over the past decade, we have learnedhow maternal diet modifies the fetal and postnatal genome substantially andcontributes to deleterious health outcomes for the developing offspring[1–3]. There is also compelling evidence that obesity and high-fatfeeding during pregnancy and lactation can have lasting consequences onbrain development and behavior. For example, children born to obese mothershave a higher risk of having symptoms ofattention-deficit/hyperactivity disorder (ADHD) than children ofnormal weight mothers [4]. Similarly, in rodents the consumption of ahigh-fat diet during pregnancy and lactation impairs hippocampal developmentwith lasting consequences on spatial learning performance in the offspring[5,6]. Accumulating evidence also indicates that maternal and earlypostnatal obesity also perturbs the development of CNS pathways that areinvolved in energy balance regulation. This chapter will review the widescope of structural and molecular changes that have been observed inspecific brain regions involved in appetite regulation, in particular thehypothalamus, when individuals are exposed to an obesogenic environmentduring perinatal life.

Anatomy and development ofhypothalamic circuits thatare involved in energy balance

Hypothalamic circuits controlling energy balance

Our current understanding of the physiological mechanisms that underliehunger and satiety is scarcely 20 years old (see [7,8] for review). In 1994,the discovery of leptin, a hormone secreted by fat cells that acts on thebrain to blunt feeding behavior and permits energy expenditure, led to aparadigm shift in our understanding with the realization that oursubconscious motivation to eat can be powerfully and dynamically regulatedby hormonal signals. This discovery was followed by the discovery of ghrelinin 2000, a hormone secreted from the stomach to promote hunger. The brainsites of action of these hormones have been extensively mapped. Inparticular, leptin and ghrelin act within complex neuronal networks in thehypothalamus that are responsible for the regulation of energy balance (see[9,10] for review; Figure 11.1). In these neuronal networks, neurons of thearcuate nucleus of the hypothalamus are of primary importance. Onesubpopulation of arcuate neurons co-expresses neuropeptide Y (NPY) andAgouti-related peptide (AgRP), which act as major orexigenic signals.