High-Fat Diet Induces MASLD and Adipose Tissue Changes in Obesity-Resistant Rats

Abstract

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.

Keywords: Obesity Resistance ; Metabolic Dysfunction-Associated Steatotic Liver Disease ; High-Fat-Diet ; Insulin Resistance ; Adipose Tissue.