Recombinant human IGF-1 alleviates dyslipidemia induced by lactational maternal dietary restriction.

BACKGROUND

Extrauterine growth restriction (EUGR) critically impacts preterm infants, often due to nutritional deficiency. Lactational protein restriction can disrupt offspring glucose/lipid metabolism by altering gene expression and increasing branched-chain amino acid catabolism.

OBJECTIVE

This study aimed to investigate the effects of postpartum maternal dietary restriction (MDR) on growth and lipid metabolism in Sprague-Dawley (SD) rat offspring, and to explore the underlying mechanisms through Agilent microarray-based transcriptomic analysis.

METHODS

An EUGR rat model was established by maternal dietary restriction. Body weight, body length, serum insulin-like growth factor-1 (IGF-1), and lipid profiles were monitored from postnatal day 1 to day 21. To evaluate therapeutic effects, a separate cohort of EUGR pups received recombinant human IGF-1 (rhIGF-1) or PBS. Liver transcriptomic analysis was conducted to identify differentially expressed genes. Based on transcriptomic results, lipoprotein lipase (LPL) was overexpressed in HepG2 cells for in vitro functional validation.

RESULTS

At 3 weeks of age, EUGR pups showed significantly lower body weight and length than controls (p < 0.01). Serum triglycerides (TG) were reduced in EUGR rats (p < 0.05), whereas total cholesterol and HDL-C were elevated. rhIGF-1 treatment did not improve growth, but significantly reduced HDL-C compared with PBS. Liver transcriptomics revealed altered expression of lipid-metabolism genes in EUGR animals; notably, LPL expression was increased. In HepG2 cells, LPL overexpression significantly downregulated the lipogenic genes ACACA and SCD (p < 0.01).

CONCLUSION

Maternal dietary restriction induces EUGR in rats, characterized by growth impairment and dyslipidemia. rhIGF-1 treatment failed to improve growth but modulated HDL-C levels. Liver transcriptomics in EUGR animals show upregulation of LPL, and in vitro experiments demonstrate that LPL can downregulate ACACA and SCD, suggesting that the LPL/ACACA/SCD pathway may underlie the observed triglyceride alterations in EUGR.