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

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Haddad-Tovolli, Roberta ; Altirriba, Jordi ; Obri, Arnaud ; Eyre Sanchez, Elena ; Chivite, Inigo ; Mila-Guasch, Maria ; Ramirez, Sara ; Gomez-Valades, Alicia G. ; Pozo, Macarena ; Burguet, Jasmine ; Velloso, Licio A. ; Claret, Marc

• Document type: Journal article
• Source: MOLECULAR METABOLISM; v. 36, p. 11-pg., 2020-06-01.

Abstract

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. (C) 2020 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). (AU)

• FAPESP's process: 16/01868-2 - Translatome analysis of mouse POMC neurons and epigenetic analysis of the median eminence BBB in diet-induced obese offspring
• Grantee: Roberta Haddad Tóvolli
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor