Pro-opiomelanocortin (POMC) neuron translatome signatures underlying obesogenic gestational malprogramming in mice

• Main Authors: Roberta Haddad-Tóvolli (Author), Jordi Altirriba (Author), Arnaud Obri (Author), Elena Eyre Sánchez (Author), Iñigo Chivite (Author), Maria Milà-Guasch (Author), Sara Ramírez (Author), Alicia G. Gómez-Valadés (Author), Macarena Pozo (Author), Jasmine Burguet (Author), Licio A. Velloso (Author), Marc Claret (Author)
• Format: Book
• Published: Elsevier, 2020-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Objective: Maternal unbalanced nutritional habits during embryonic development and perinatal stages perturb hypothalamic neuronal programming of the offspring, thus increasing obesity-associated diabetes risk. However, the underlying molecular mechanisms remain largely unknown. In this study we sought to determine the translatomic signatures associated with pro-opiomelanocortin (POMC) neuron malprogramming in maternal obesogenic conditions. Methods: We used the RiboTag mouse model to specifically profile the translatome of POMC neurons during neonatal (P0) and perinatal (P21) life and its neuroanatomical, functional, and physiological consequences. Results: Maternal high-fat diet (HFD) exposure did not interfere with offspring's hypothalamic POMC neuron specification, but significantly impaired their spatial distribution and axonal extension to target areas. Importantly, we established POMC neuron-specific translatome signatures accounting for aberrant neuronal development and axonal growth. These anatomical and molecular alterations caused metabolic dysfunction in early life and adulthood. Conclusions: Our study provides fundamental insights on the molecular mechanisms underlying POMC neuron malprogramming in obesogenic contexts.

Item Description

2212-8778
10.1016/j.molmet.2020.02.006