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Diet Processing and Nutrient Composition Drive Divergent Obesity Phenotypes in Wistar Rats

Tenorio, P. R.; e Silva, G. S. S.; Quadreli, D. H.; Fernandes, G. S. A.; de Andrade, F. G.

2025-07-22 physiology
10.1101/2025.07.17.665389 bioRxiv
Show abstract

Obesity is a multifactorial condition influenced not only by diet composition but also by food processing. While high-fat and high-sugar diets are widely used in rodent models of metabolic syndrome, the independent effects of diet purification remain poorly understood. This study evaluated the impact of a grain-based control (C/GB), a balanced semi-purified (B/SP), and a high-fat/high-sugar semi-purified (HFS/SP) diet on obesity development and metabolic alterations in adult male Wistar rats over 10 weeks. Morphometric, biochemical, histological, metabolic, and oxidative parameters were assessed. Rats fed the B/SP diet exhibited greater body weight and adiposity despite similar caloric intake, yet these changes were largely compensatory, with enhanced fat mobilization, redistribution toward subcutaneous depots, and improved antioxidant defenses. In contrast, HFS/SP-fed rats consumed fewer calories but developed visceral adiposity without additional body weight, in association with reduced fat mobilization and oxidation. Only the HFS/SP group displayed features of metabolic syndrome, including impaired glucose control, dyslipidemia, hepatic steatosis, and systemic as well as tissue oxidative stress. The liver emerged as a central organ mediating oxidative burden, reinforcing its key role in obesity-related metabolic impairment. In conclusion, our findings demonstrate that both nutrient composition and diet purification shape distinct obesity phenotypes, but only high-fat/high-sugar intake determines the risk of metabolic dysfunction. HIGHLIGHTS* Diet purification contributes to adipose tissue and weight gain. * Diet purification alone does not induce metabolic damage. * Diet composition is the main contributor to the development of metabolic syndrome.

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