Temporal Changes in Hepatic Fatty Acid Metabolism, Desaturase Expression, and Lipid Peroxidation During Long-Term Sucrose Feeding in Male and Female Rats

Background/Objectives: Chronic sucrose consumption may contribute to progressive metabolic dysfunction, but the combined influence of long-term exposure, aging, sex, and dietary fiber on hepatic lipid metabolism remains insufficiently understood. This study investigated how time and sex influence hepatic lipid metabolism during chronic sucrose supplementation and characterized responses under different dietary backgrounds. Methods: A total of 120 Wistar Han rats (60 males and 60 females) were allocated to four dietary treatments: control diet (CON), control diet with increased fiber content (CON-fiber), 30% sucrose in drinking water (HS), or 30% sucrose in drinking water with high fiber content (HS-fiber). Five animals of each sex per treatment were euthanized after 1, 12, or 24 months. Glucose homeostasis, hepatic fatty-acid composition, serum malondialdehyde (MDA), and hepatic expression of SCD1, Fads1, Fads2, NRF2, TNFα, and TGFβ were evaluated. Results: Treatment effects became prominent after 12 and 24 months. Chronic sucrose intake increased body mass in HS rats, impaired glucose homeostasis and insulin sensitivity, shifted the hepatic fatty-acid profile toward monounsaturated fatty acids, and reduced several n-3 and n-6 polyunsaturated fatty acids. Increased SCD1 expression accompanied increased relative proportions of palmitoleic and oleic acids, whereas Fads1 and Fads2 showed treatment-associated differences within individual sampling points. Sucrose-exposed groups also developed increased lipid peroxidation and a pro-inflammatory transcriptional response. Conclusions: Metabolic, oxidative, and inflammatory alterations were observed in sucrose-fed groups, with treatment-associated differences depending on sex and sampling time point. These findings emphasize the importance of exposure duration and biological sex in shaping metabolic responses during aging.