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High-Fat Diet Induces MASLD and Adipose Tissue Changes in Obesity-Resistant Rats
Amanda Rangel Madureira1,2, Vinicius Valois Pereira Martins1, Janete Corrêa Cardoso2
1Postgraduate Program in Nutrition and Health, Health Sciences Center, Department of Integrated Health Education, Federal University of Espírito Santo, Vitória, (Espírito Santo), Brazil.
Background/Aims:
Obesity Resistance (OR) is characterized by limited weight gain and reduced fat accumulation despite an obesogenic diet. However, the metabolic risk, particularly regarding Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), remains unclear. The current study aims to investigate the presence of MASLD, as well as metabolic parameters and morphological aspects of adipose tissues in obesity-resistant (OR) R rats fed a high-fat diet (HFD).
Methods:
ale Wistar rats (n=71) were initially randomized into two groups: a) standard diet (SD, n=35) and b) high-fat diet (HFD, n=36). The protocol was performed for 14 weeks, including 4 weeks of induction and 10 weeks of exposure to obesity. Subsequently, after applying the tertile classification criterion, the animals were redistributed into three groups: a) control (C, n=12), fed a standard diet; b) obesity-prone (OP, n=12); and c) OR (n=12). Body weight evolution, adiposity, nutritional behavior, metabolic markers, and liver morphology were assessed, along with the staging of MASLD.
Results:
OR rats exhibited lower body weight, total fat pads, and leptin compared to OP but higher values than C. MASLD was observed in 50% of OR animals, while 37.5% progressed to metabolic dysfunction-associated steatohepatitis (MASH). OP rats had a higher incidence of MASH (87.5%).
Conclusion:
Chronic HFD exposure in OR rats lead to metabolic changes and MASLD development, including MASH, demonstrating that OR does not protect against HFD-induced hepatic alterations.
Insights
Obesity-resistant rats fed a high-fat diet developed Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), including MASH. Obesity resistance does not prevent diet-induced liver damage.
Area of Science:
- Metabolic research
- Hepatology
- Obesity studies
Background:
- Obesity resistance (OR) limits weight gain but its impact on metabolic risk, specifically Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), is not fully understood.
- Investigating MASLD and metabolic parameters in obesity-resistant rats on a high-fat diet (HFD) is crucial for understanding metabolic health.
- Adipose tissue morphology and MASLD staging are key indicators of metabolic dysfunction.
Purpose of the Study:
- To investigate MASLD development in obesity-resistant rats.
- To assess metabolic parameters and adipose tissue morphology in rats fed a high-fat diet.
- To determine if obesity resistance protects against diet-induced hepatic alterations.
Main Methods:
- Male Wistar rats were fed standard or high-fat diets for 14 weeks.
- Animals were classified into control, obesity-prone (OP), and obesity-resistant (OR) groups based on tertiles.
- Evaluated body weight, adiposity, metabolic markers, liver morphology, and MASLD staging.
Main Results:
- Obesity-resistant rats had lower body weight, fat pads, and leptin than obesity-prone rats, but higher than controls.
- MASLD was present in 50% of obesity-resistant rats, with 37.5% progressing to MASH.
- Obesity-prone rats showed a higher incidence of MASH (87.5%).
Conclusions:
- Chronic high-fat diet exposure induces metabolic changes and MASLD in obesity-resistant rats.
- Obesity resistance does not confer protection against high-fat diet-induced liver disease.
- These findings highlight the importance of diet quality even in metabolically resilient individuals.
