Lycopene: Protective Potential Against Diet-Induced Metabolic Derangements in Wistar Rats

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University of the Witwatersrand, Johannesburg

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Early-life nutrition and dietary supplements significantly impact long-term health by either increasing the risk of metabolic disorders or enhancing well-being in adulthood. Lycopene has potent antioxidant activity hence this study evaluated its potential to protect against dietary fructose-induced metabolic derangements in Wistar rats mimicking adolescents fed an obesogenic diet. Ninety-six 21-day-old Wistar rats (48 females and 48 males) were assigned to different groups at random and received treatment regimens for 12 weeks as follows: (1) standard rat chow (SRC) with plain drinking water (PDW) and plain gelatine cubes (PG), (2) SRC with a 20% fructose solution (FS) and PG, (3) SRC with FS and 100 mg/kg/day fenofibrate in gelatine cubes. Groups 4, 5, and 6 had SRC, FS, and lycopene in gelatine cube at 30, 60, and 100 mg/kg/day, respectively. Feed and fluid consumption, and body mass, were measured. Terminally, the fasted rats were weighed and euthanised. Collected blood was used to assess treatment effects on general health and oxidant and antioxidant status. Gastrointestinal viscera macro-morphometry, visceral and epididymal fat, liver fat, and kidney and liver macro- and micro-morphometry and femora and tibiae indices were determined. Female and male rats fed the control diet had higher (p < 0.05) feed intake compared to high fructose diet fed, fenofibrate treated and lycopene supplemented counterparts. Compared to control diet fed and fenofibrate-treated, lycopene-supplemented rats had lower feed intake but higher fluid intake (p < 0.05). Both female and male rats showed significant growth during the trial (p < 0.05). Lycopene increased the small intestine and stomach masses in male rats. Treatment regimens did not affect visceral fat in either male or female rats, nor epididymal fat mass in males (p > 0.05). Fenofibrate increased the females’ high-density lipoprotein (HDL), glycated haemoglobin (HbA1c), and fasting blood glucose (FBG) concentrations, and the males’ FBG concentration (p < 0.05). The rats’ haemoglobin, haematocrit, triglycerides, serum total cholesterol, low-density lipoprotein (LDL), leptin, creatinine, blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), and thiobarbituric acid reactive substances (TBARS) concentrations, BUN/creatinine ratio, alanine aminotransferase (ALT), gamma- glutamyl transferase (GGT), aspartate aminotransferase (AST), and glutathione peroxidase 1 (GPX-1) activities, glomerular tuft area, proximal convoluted tubule outer and epithelial areas showed no significant changes across treatment groups (p > 0.05). Lycopene prevented fructose- induced increase in urinary space observed in male rats. In females, treatments did not affect serum viii globulin, total protein, albumin, bile acids and uric acid concentrations (p > 0.05). Supplemental lycopene attenuated dietary fructose-induced serum albumin, total protein, globulin, total bile acids, and uric acid increases concentrations in males. High-dose supplemental lycopene increased hepatic GPX-1 and catalase (CAT) activities in male rats. In both sexes fenofibrate caused hepatocyte hypertrophy. Lycopene mitigated dietary fructose-induced increases in liver lipid content and steatosis. Dietary fortification with lycopene showed significant prophylactic potential against metabolic disturbances caused by dietary fructose in Wistar rats. It improved bone, kidney, liver, and gastrointestinal health and enhanced antioxidant activity, supporting better metabolic outcomes and overall well-being in both sexes.

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A research report submitted in fulfillment of the requirements for the Doctor of Philosophy, in the Faculty of Health Sciences, School of Physiology, University of the Witwatersrand, Johannesburg, 2025

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Shafe, Mercy Omoye. (2025). Lycopene: Protective Potential Against Diet-Induced Metabolic Derangements in Wistar Rats [PhD thesis, University of the Witwatersrand, Johannesburg]. WIReDSpace. https://hdl.handle.net/10539/48451

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