Unraveling Puerarin's impact on MRI hepatic lipid deposition and serum lipids in IUGR offspring rats.

Intrauterine growth restriction (IUGR) is associated with long-term metabolic programming effects, including hepatic structural alterations and later-life susceptibility to metabolic disease, potentially involving dysregulation of peroxisome proliferator-activated receptor alpha (PPARα), a key regulator of hepatic fatty acid oxidation. Given its established antioxidant and lipid-modulating properties in adult models of metabolic syndrome, puerarin, a natural isoflavone, was evaluated as an early-life intervention to mitigate hepatic injury in IUGR offspring. An IUGR rat model was established via gestational protein restriction. Male offspring were randomized into Control, IUGR, and IUGR plus puerarin groups. Separate cohorts (n = 6 per group per time point) were assessed at weeks 3, 8, and 12. Puerarin (50 mg/kg/day) was administered intraperitoneally from postnatal days 7-21. Hepatic tissue characteristics were evaluated using T1 mapping and intravoxel incoherent motion (IVIM) MRI. Serum lipid profiles and hepatic PPARα mRNA expression were also measured. Data were analyzed using two-way ANOVA followed by Tukey's post hoc test. IUGR offspring exhibited significantly elevated hepatic T1 relaxation times from week 3 onward (P < 0.0001), indicating early and persistent hepatic microstructural alterations. Serum lipid parameters remained largely comparable across all groups, with no significant intergroup differences in TG, TC, LDL-C, or HDL-C at individual time points. Puerarin treatment significantly reduced T1 values and improved diffusion-related parameter (D) across all time points (P < 0.05), indicating improved hepatic water mobility and microstructural integrity. ADC showed early improvement at week 3, whereas perfusion-related IVIM parameters (D* and F) showed no consistent or significant intergroup differences. Serum TG levels were significantly reduced by puerarin at week 12 compared with untreated IUGR offspring (P < 0.05), while TC and LDL-C remained unchanged. Hepatic PPARα expression was markedly suppressed in IUGR offspring across all time points (P < 0.0001) and was significantly increased by puerarin only at week 12 (P < 0.01), although overall expression remained below control levels. These findings suggest that IUGR primarily induces early hepatic microstructural alterations detectable by quantitative MRI before overt systemic dyslipidemia. Early-life puerarin intervention partially ameliorates hepatic diffusion abnormalities and improves selected metabolic markers, potentially through delayed activation of lipid oxidation pathways including PPARα. However, further studies incorporating direct hepatic lipid quantification and functional metabolic assessments are required to validate these findings.