Intralipid Infusion to Fetal Sheep ( <scp> <i>Ovis aries</i> </scp> ) Promotes Differentiation and Lipid Accumulation of Adipose Tissues

Intralipid is a lipid emulsion used for preterm infants, but its biological effects on adipose development remain poorly examined. We investigated the effects of intravenous Intralipid on the adipose tissue development of midgestation fetal sheep. Intralipid20 infusion was started in fetuses at 88-90 days of gestation (dG) following clinical infant dosing guidance (0.5-1 g/kg/d estimated body weight, increasing daily by 0.5-1 g/kg/d to a maximum of 3 g/kg/d). Intralipid increased perirenal fat weight, adipocyte size, and lipid accumulation. Expression of key adipogenic genes was upregulated, including Pparg (Peroxisome Proliferator-Activated Receptor Gamma), Fasn (Fatty Acid Synthase), Fabp4 (Adipocyte Fatty Acid Binding Protein 4), Acca (Acetyl-CoA Carboxylase α), and Cebpa (CCAAT/Enhancer-Binding Protein Alpha), while downregulating Pdgfra (Platelet-Derived Growth Factor Receptor Alpha), Cidea (Cell death-inducing DNA fragmentation factor α-like effector A), Ppargc1a (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha), and Ucp1 (Uncoupling Protein 1). Similar changes were confirmed in omental fat. Intralipid elicited mild inflammation in both perirenal and omental fat by increasing the expression of Tnfa (Tumor Necrosis Factor-Alpha), with upregulation of Tlr4 (Toll-Like Receptor-4), and Tlr2 (Toll-Like Receptor-2) specifically in perirenal fat. Notably, this inflammatory response occurred without elevation of Il-6 (Interleukin-6) expression or NF-κB activation. Moreover, Intralipid treatment suppressed the expression of fibrosis-related genes, including Lh2b (lysyl oxidase-like 2b) and P4ha (prolyl 4-hydroxylase). These findings suggest that Intralipid administration at a developmental stage prior to normal term enhances ovine adipogenic differentiation and lipid accumulation which might be protective to premature infants, but it might slightly induce inflammation in the adipose tissues.