Abstract
Anorexia nervosa (AN) is a dramatic psychiatric disorder characterized by dysregulations in food intake and reward processing, involving molecular and cellular changes in several peripheral cell types and central neuronal networks. Genomic and epigenomic analyses have allowed the identification of multiple genetic and epigenetic modifications highlighting the complex pathophysiology of AN. Behavioral and genetic rodent models have been used to recapitulate and investigate, with some limitations, the cellular and molecular changes that potentially underlie eating disorders. In the last 5 years, the use of induced pluripotent stem cells (IPSCs), combined with CRISPR–Cas9 technology, has led to the generation of specific neuronal cell subtypes engineered from human somatic samples, representing a powerful tool to complement observations made in human samples and data collected from animal models. Systems biology using IPSCs has indeed proved to be a valuable approach for the study of metabolic disorders, in addition to neurodevelopmental and psychiatric disorders. The manuscript, while reviewing the main findings related to the genetic, epigenetic, and cellular bases of AN, will present how new studies published, or to be performed, in the field of IPSC-derived cells should improve our current understanding of the pathophysiology of AN and provide potential therapeutic strategies addressing specific endophenotypes.
Highlights
ANOREXIA NERVOSA, A MULTIFACTORIAL DISORDERAnorexia nervosa (AN), the psychiatric disorder with the highest suicide rate, estimated at 10% per decade, is prevalent in 0.5% of the general population and has a sex ratio of nine females to one male [1]
In the last 5 years, the use of induced pluripotent stem cells (IPSCs), combined with CRISPR–Cas9 technology, has led to the generation of specific neuronal cell subtypes engineered from human somatic samples, representing a powerful tool to complement observations made in human samples and data collected from animal models
Besides the human samples used to investigate the potential genetic and epigenetic components of eating disorders such as AN, animal models have been used to better understand the genes involved in and the mechanism that control the regulation of food intake, reward processing, and eating behaviors that may depend on environmental stress conditions
Summary
Anorexia nervosa (AN) is a dramatic psychiatric disorder characterized by dysregulations in food intake and reward processing, involving molecular and cellular changes in several peripheral cell types and central neuronal networks. Behavioral and genetic rodent models have been used to recapitulate and investigate, with some limitations, the cellular and molecular changes that potentially underlie eating disorders. In the last 5 years, the use of induced pluripotent stem cells (IPSCs), combined with CRISPR–Cas technology, has led to the generation of specific neuronal cell subtypes engineered from human somatic samples, representing a powerful tool to complement observations made in human samples and data collected from animal models. The manuscript, while reviewing the main findings related to the genetic, epigenetic, and cellular bases of AN, will present how new studies published, or to be performed, in the field of IPSC-derived cells should improve our current understanding of the pathophysiology of AN and provide potential therapeutic strategies addressing specific endophenotypes
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