Introduction

The perinatal environment exerts profound effects on the structure and function of the mammalian central nervous system (CNS). Although certain experiences are essential for orderly brain development to proceed, the occurrence of some harmful experiences can also have deleterious consequences on the developing brain. Over the past decade, we have learned how maternal diet modifies the fetal and postnatal genome substantially and contributes to deleterious health outcomes for the developing offspring [1–3]. There is also compelling evidence that obesity and high-fat feeding during pregnancy and lactation can have lasting consequences on brain development and behavior. For example, children born to obese mothers have a higher risk of having symptoms of attention-deficit/hyperactivity disorder (ADHD) than children of normal weight mothers [4]. Similarly, in rodents the consumption of a high-fat diet during pregnancy and lactation impairs hippocampal development with lasting consequences on spatial learning performance in the offspring [5,6]. Accumulating evidence also indicates that maternal and early postnatal obesity also perturbs the development of CNS pathways that are involved in energy balance regulation. This chapter will review the wide scope of structural and molecular changes that have been observed in specific brain regions involved in appetite regulation, in particular the hypothalamus, when individuals are exposed to an obesogenic environment during perinatal life.

Anatomy and development of hypothalamic circuits that are involved in energy balance

Hypothalamic circuits controlling energy balance

Our current understanding of the physiological mechanisms that underlie hunger 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 the brain to blunt feeding behavior and permits energy expenditure, led to a paradigm shift in our understanding with the realization that our subconscious motivation to eat can be powerfully and dynamically regulated by hormonal signals. This discovery was followed by the discovery of ghrelin in 2000, a hormone secreted from the stomach to promote hunger. The brain sites of action of these hormones have been extensively mapped. In particular, leptin and ghrelin act within complex neuronal networks in the hypothalamus that are responsible for the regulation of energy balance (see [9,10] for review; Figure 11.1). In these neuronal networks, neurons of the arcuate nucleus of the hypothalamus are of primary importance. One subpopulation of arcuate neurons co-expresses neuropeptide Y (NPY) and Agouti-related peptide (AgRP), which act as major orexigenic signals.