Metabolic programming by early-life stress exposure Focus on sex differences

Exposure to early-life stress (ES), such as neglect or abuse, is common in modern society. ES exposure increases the risk for developing a range of disorders, including metabolic diseases (e.g. obesity) as well as mental and cognitive disorders. Prevention of ES is difficult, and a better understanding of the biological underpinnings is needed to develop effective intervention strategies.
The concept that the early-life environment shapes the offspring is called ‘programming’. However, the mechanisms by which ES programs offspring for life are unclear. We therefore studied i) whether there is a role for early-life nutrition in programming by ES; ii) if ES affects the choice for unhealthy dietary components, the physiological response to such an unhealthy diet, as well as the underlying brain circuitries that regulate food intake and metabolism; iii) whether mitochondria could be a subcellular substrate for programming by ES; and iv) if the effects of ES are similar for males and females.
In this thesis, we show that stress alters the milk and offspring fatty acid status, suggesting that the maternal milk composition could be involved in programming by ES. Moreover, we show that ES affects food choice, the adipose tissue and the neurobiological substrates regulating food intake and energy expenditure in a sex-specific manner. Finally, on a subcellular level, we reveal that mitochondria are affected by ES in both peripheral and central tissues.
This thesis contributes to a better understanding of how ES shapes individuals for life and can help the future development of targeted therapeutic strategies.