Characterization of an experimental high-fat diet-induced obesity model in mice for studies of obesity-associated arthritis

Obesity is an important factor to the progression and severity of rheumatoid arthritis (RA), as it promotes a state of chronic low-grade systemic inflammation associated with increased disease activity and impaired therapeutic response [1–6]. Experimental models that recapitulate the metabolic and inflammatory alterations induced by obesity are essential for elucidating the immunometabolic mechanisms underlying this association and for enabling the preclinical evaluation of therapeutic strategies. C57BL/6 mice were randomly assigned to receive either a standard diet (SD) or a high-fat diet (HFD) for 12 weeks. Body weight, food intake, and blood glucose levels were monitored weekly. Beginning at week 8, animals were euthanized at predefined time points to determine the relative weights of the liver, spleen, visceral adipose tissue (VAT), and white adipose tissue (WAT). Additionally, the body mass index (BMI) and abdominal circumference were assessed to characterize the metabolic alterations induced by the HFD. The HFD induced a progressive increase in body weight in both sexes, with a more pronounced effect in males. Despite lower food intake, HFD-fed mice exhibited greater weight gain than SD-fed animals, consistent with the higher energy density of the diet. Fasting blood glucose levels were modestly increased in the HFD groups. Organ and tissue analysis revealed a marked expansion of VAT and WAT, particularly in males, along with changes in liver and spleen weights. Collectively, these findings demonstrate that the protocol successfully established a reproducible model of diet-induced obesity in C57BL/6 mice, characterized by increased adiposity and metabolic alterations. This model provides a robust experimental platform for investigating the immunometabolic mechanisms underlying obesity-associated arthritis, notably the contribution of adipose tissue to the exacerbation of inflammatory response, and for the preclinical evaluation of new therapeutic strategies.