Starvation-induced changes in somatic insulin/IGF-1R signaling drive metabolic programming across generations

Exposure to adverse nutritional and metabolic environments during critical periods of development can exert long-lasting effects on health outcomes of an individual and its descendants. Although such metabolic programming has been observed in multiple species and in response to distinct nutritional stressors, conclusive insights into signaling pathways and mechanisms responsible for initiating, mediating, and manifesting changes to metabolism and behavior across generations remain scarce. By using a starvation paradigm in Caenorhabditis elegans, we show that starvation-induced changes in dauer formation-16/forkhead box transcription factor class O (DAF-16/FoxO) activity, the main downstream target of insulin/insulin-like growth factor 1 (IGF-1) receptor signaling, are responsible for metabolic programming phenotypes. Tissue-specific depletion of DAF-16/FoxO during distinct developmental time points demonstrates that DAF-16/FoxO acts in somatic tissues, but not directly in the germline, to both initiate and manifest metabolic programming. In conclusion, our study deciphers multifaceted and critical roles of highly conserved insulin/IGF-1 receptor signaling in determining health outcomes and behavior across generations.

Automated summary

Exposure to adverse nutritional and metabolic environments during critical periods of development can have lasting effects on individuals and their descendants. However, the specific signaling pathways and mechanisms responsible for these effects are still not well understood. Through experiments with Caenorhabditis elegans, researchers have discovered that changes in DAF-16/FoxO activity, a downstream target of insulin/IGF-1 receptor signaling, are responsible for metabolic programming phenotypes. The study also found that DAF-16/FoxO acts in somatic tissues, rather than directly in the germline, to initiate and manifest these programming effects.