# Targeting Heightened Inflammatory Tone in IUGR Neonatal Lambs via Daily Oral Supplementation of ω-3 PUFA Improved Growth Rates, Muscle Mass, and Adiponectin Signaling

## TL;DR

Supplementing ω-3 PUFA in IUGR lambs improved growth, muscle mass, and adiponectin signaling by reducing inflammation.

## Contribution

Daily oral ω-3 PUFA supplementation resolves growth deficits in IUGR lambs by targeting neonatal inflammation.

## Key findings

- ω-3 PUFA supplementation fully resolved bodyweight deficits in IUGR lambs by day 28.
- ω-3 PUFA improved subcutaneous fat, visceral organ growth, and skeletal muscle mass in IUGR lambs.
- ω-3 PUFA restored myoblast populations and AdipoR2 content, resolving asymmetric growth restriction.

## Abstract

Background/Objectives: Circulating inflammatory cytokines and tissue sensitivity are both elevated following heat stress-induced intrauterine growth restriction (IUGR). Cytokines disrupt myoblast function and muscle growth, and thus we hypothesized that suppressing inflammatory tone in IUGR-born lambs by supplementing anti-inflammatory nutraceuticals would improve early postnatal growth. Methods: IUGR lambs produced by maternal heat stress were supplemented daily with 42 mg/kg oral omega-3 polyunsaturated fatty acid (ω-3 PUFA) Ca2+ salts or placebo from birth to 28 days of age. Results: By day 28, the 21% lighter bodyweights for IUGR lambs were fully resolved by ω-3 PUFA due to the complete recovery of average daily gain. Subcutaneous fat deposition and visceral organ growth were modestly diminished in IUGR-born lambs, but skeletal muscle mass was more markedly restricted. This coincided with 63% less muscle AdipoR2 but 27% greater circulating adiponectin. ω-3 PUFA reduced or eliminated deficits in subcutaneous fat, visceral organs, and five of the six individual muscles assessed, which corresponded with rescue of myoblast populations and AdipoR2 content. In turn, asymmetric growth restriction was resolved at one month of age. Conclusions: These findings show that targeting heightened inflammatory tone during the neonatal period in IUGR-born offspring can recover early growth in skeletal muscle and other soft tissues.