# Gestational low-protein diet impairs mitochondrial function and skeletal muscle development by inducing immune responses in male offspring

## TL;DR

A low-protein diet during pregnancy harms muscle development in male offspring by triggering immune responses and disrupting energy metabolism.

## Contribution

This study reveals how gestational low-protein diets impair skeletal muscle development and mitochondrial function in male offspring.

## Key findings

- Gestational low-protein diet increases immune response and inflammation in offspring skeletal muscle.
- Protein restriction during pregnancy reduces muscle fiber number and disrupts energy metabolism.
- Gestational low-protein diet causes oxidative stress and mitochondrial dysfunction in offspring.

## Abstract

Maternal nutrition is essential for proper fetal and postnatal organ maturation and is linked to the future risk of developing metabolic syndrome, cardiovascular disease, and muscle loss. There is still limited understanding how a low-protein intake during gestation influences skeletal muscle development, inflammation, and the related pathways. This study aimed to investigate the impact of gestational low-protein diet in mice on skeletal muscle development and inflammatory responses in male offspring.

Pups born from mothers fed a low-protein diet (LPD) were lactated by normal protein diet (NPD)-fed mothers and maintained on NPD post-weaning (LNN group). Offspring born from mothers fed an NPD and maintained on an NPD during lactation and beyond were used as controls (NNN group).

In 21-day-old offspring from protein-restricted mothers, RNA-Seq analysis showed upregulation of immune response–related genes, enriching adaptive immunity pathways. Additionally, LNN group exhibited elevated markers of inflammation, along with disruptions in antioxidant defence balance and macrophages infiltration in gastrocnemius muscle at 3 months of age. Energy metabolism was impaired, as indicated by changes in related proteins and enzymes involved in mitochondrial function.

We conclude that gestational LPD adversely affects skeletal muscle development in male offspring.

•Gestational protein restriction induces an offspring immune response.•Gestational protein restriction leads to decreased fibre number in offspring muscle.•Gestational protein restriction disrupts muscle energy metabolism.•Gestational protein restriction increases muscle oxidative stress.

Gestational protein restriction induces an offspring immune response.

Gestational protein restriction leads to decreased fibre number in offspring muscle.

Gestational protein restriction disrupts muscle energy metabolism.

Gestational protein restriction increases muscle oxidative stress.