Developmental Programming of Nonalcoholic Fatty Liver Disease (NAFLD)

Abstract

Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide and is present in a third of the general population and the majority of individuals with obesity and type 2 diabetes. The less severe form of the disease is relatively common and can be somewhat benign. However, in certain individuals, the disease can progress to the more severe nonalcoholic steatohepatitis (NASH), resulting in a poor health, a poor prognosis, and a significant healthcare burden. In recent years, there has been a major research effort focused on identifying the factors that promote NALFD disease progression, and as a result there has been a significant advancement in our understanding of the interaction between nutrition and the molecular mechanisms that regulate hepatic lipid homeostasis. Nonetheless, the capacity of the maternal diet to alter these fundamental metabolic pathways and thus prime the development of severe fatty liver disease in the adult liver has proved to be one of the most striking findings from this body of research. Since the prudence of the maternal diet has wavered in recent years, this may explain why NAFLD-once commonly associated with older individuals-is now increasingly common in young adults, children, and adolescents. In the following chapter, we aim to review the current hypothesis surrounding the mechanisms that underlie the developmental priming of NAFLD. We will also explore how these novel insights have facilitated the emergence of promising new pharmacological and nutritional intervention strategies.