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

https://doi.org/10.1016/j.molmet.2020.02.006Get rights and content
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Highlights

  • Cell-specific POMC neuron translatome profiling in neonatal and perinatal developmental stages.

  • Maternal obesogenic environment alters progeny's POMC neuron translatome signatures.

  • Maternal HFD impairs POMC spatial distribution and axonal outgrowth, which is related to offspring's metabolic dysfunction.

  • The HFD intervention stage (early life or adulthood) differentially impact POMC neuron transcriptional signatures.

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.

Keywords

POMC neuron
RiboTag
Neuronal programming
Obesity
Translatome

Cited by (0)

7

Roberta Haddad-Tóvolli and Jordi Altirriba contributed equally to this work.

8

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