Lipid emulsion modulates myogenic and collagen‐related gene expression in skeletal muscle of preterm fetal sheep

Abstract Although intravenous lipid emulsions are routinely administered to preterm infants, their specific effects on skeletal muscle development remain unclear. In this study, a soybean oil‐based lipid emulsion (Intralipid 20®) was administered via intravenous infusion to fetal sheep (gestational day 88–90) at a dose rising from 1 g/kg/day (day 0) to 3 g/kg/day (days 2–8). Intralipid infusion did not alter overall fetal body weight, tibialis anterior (TA) muscle mass or serum testosterone levels. Histological analyses revealed no significant differences in muscle fibre diameter or collagen content in TA muscles between groups. However, Intralipid significantly upregulated the expression of key myogenic regulatory genes, including Myog (myogenin) and Myod (myogenic differentiation 1), while downregulating the expression of several genes associated with fibrogenesis: Col1a1 (collagen type I α1 chain), Col3a1 (collagen type III α1 chain), Lh2b (lysyl hydroxylase 2b) and P4ha (prolyl 4‐hydroxylase α). In contrast, Intralipid had no significant effect on the expression of genes associated with intramuscular adipogenesis, including Pparg (peroxisome proliferator‐activated receptor γ), Pdgfra (platelet‐derived growth factor receptor α), Zfp423 (zinc finger protein 423), Slc27a1 (solute carrier family 27 member 1), C/ebpa (CCAAT/enhancer‐binding protein α) and Fasn (fatty acid synthase). Similarly, genes related to inflammation, such as Tnfa (tumour necrosis factor α), Il‐6 (interleukin 6), Tlr4 (Toll‐like receptor 4) and Tlr2 (Toll‐like receptor 2), were unaffected. In conclusion, these findings indicate that short‐term lipid exposure alters gene expression patterns without measurable structural changes, suggesting that transcriptional responses may precede overt morphological remodelling in fetal skeletal muscle.