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

Maternal unbalanced nutritional habits during embryo development and perinatal stages perturb hypothalamic neuronal programming of the offspring, thus increasing “diabesity” risk. Here we report that exposure to high-fat diet during gestation and lactation did not interfere with progeny'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 neuronal aberrant development and axonal growth. These anatomical and molecular alterations caused metabolic dysfunction in early-life and adulthood. Our study provides fundamental insights on the molecular mechanisms underlying POMC neuron malprogramming in obesogenic contexts. Overall design: Chow diet, Post-natal day 0 (5 replicates) Chow diet, Post-natal day 21 (3 replicates) High fat diet, Post-natal day 0 (5 replicates) High fat diet, Post-natal day 21 (4 replicates)