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

• Main Authors: Roberta Haddad-Tóvolli, Jordi Altirriba, Arnaud Obri, Elena Eyre Sánchez, Iñigo Chivite, Maria Milà-Guasch, Sara Ramírez, Alicia G. Gómez-Valadés, Macarena Pozo, Jasmine Burguet, Licio A. Velloso, Marc Claret
• Format: Article
• Language: English
• Published: Elsevier 2020-06-01
• Series: Molecular Metabolism
• Subjects: POMC neuron; RiboTag; Neuronal programming; Obesity; Translatome
• Online Access: http://www.sciencedirect.com/science/article/pii/S2212877820300351

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.