High‐Cholesterol Diet Supplemented With Methionine During Pregnancy Modulates Hepatic MMP‐2 and MMP‐9 Activities and Aggravates Iron Overload and Fatty Liver Development in Rabbits

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ABSTRACT During pregnancy, the maternal liver undergoes crucial metabolic adaptations that remain incompletely understood, particularly under adverse dietary conditions. This study investigates whether a high‐cholesterol diet supplemented with Methionine during pregnancy acts as an aggravating factor for hepatic disorders and alterations in matrix metalloproteinases (MMP‐2 and MMP‐9) activities. Two successive pregnancies were performed in 29 rabbits divided into standard (SD) and cholesterol‐ methionine (CMD) diet groups. The females received their respective diet 15 days before mating and then during two successive pregnancies. Lipids and iron are evaluated in the liver. Phospholipids are analyzed using thin‐layer chromatography, and the metalloproteinase MMP‐2 and MMP‐9 activities are evaluated by zymography method. A topographic (Masson) and histochemical (Nile blue, and Perl's stain) staining are used for histological study. The accumulation of hepatic lipids concerned Total Cholesterol (TC) (324%) and phospholipids (50 times) with the involvement of Phosphatidyl ethanolamine (PE), Phosphatidyl serine (PS), Phosphatidylcholine, and cardiolipin, whereas Triglycerides (TG) decrease (20.47%). The iron content increased in the CMD female liver. The liver structure showed disorganization, fibrosis associated with MMP‐2 activity rise, and inflammatory cell infiltration. Our study shows the amplified effect of successive pregnancies on structural disorders (matrix remodeling) and metabolic disorders (iron overload, lipid accumulation) caused by a cholesterol‐methionine‐enriched diet.

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