Arthritis induces Inflammatory Cell Infiltration, Oxidative Stress and Browning in Rat Perivascular Adipose Tissue

In rats submitted to adjuvant-induced arthritis (AIA), joint-derived cytokines cause sarcopenia and fat mass loss. This mass reduction was also observed in the perivascular adipose tissue (PVAT), where the inflammatory actions of arthritis are much less understood. In this context, we hypothesize that AIA causes inflammation in PVAT with its own characteristics, with temporal evolution followed by remission once the model is self-limiting. Thus, the present study aimed to characterize the temporal course of the inflammatory process caused by AIA in PVAT to identify its peak, which is the ideal moment to assess therapeutic interventions.Male 12 weeks old Wistar rats (±320g; groups of 6-8 animals) were studied healthy (control) or on the 15 th (D15), 22 nd (D22), 29 th (D29), 36 th (D36) and 43 rd (D43) day after AIA induction by intradermal administration of Mycobacterium tuberculosis (3.8mg/mL). From these animals were harvested plasma and PVAT from the aorta either thoracic (PVAT-t) or abdominal (PVAT-a). Concentrations of interleukin-10 (IL-10) and tumor necrosis factor- α (TNF- α ) in plasma, as well as TNF- α, interleukin-1 β (IL-1 β ) and interleukin-6 (IL-6) in PVAT harvested on D36 were determined by ELISA. In PVAT, it was also quantified the activity of N-acetylglucosaminidase (NAG; mononuclear cells marker) and myeloperoxidase (MPO; polymorphonuclear cells marker), the production of superoxide anion (O 2 •- ) by lucigenin chemiluminescence, the lipid peroxidation by the TBARS and mRNA expression of ASC-1 and PGC1a (marker of white and brown adipose tissue phenotype, respectively), by quantitative real-time polymerase chain reaction (qRT-PCR). It was observed that AIA has increased circulating levels of IL-10, which peaked on D29 (1.56 ± 0.3 vs. 2.93 ± 0.4 η g/mL; p<0.05) followed by a return to normal levels, while the increase of TNF- α occurred on D29 and D36 (1.46 ± 0.8 vs. 7.08 ± 1.3 η g/mL and 6.43 ± 1.4 η g/mL, p<0.05, respectively). AIA increased NAG in PVAT-a on D43 (5.4 ± 0.5 vs. 10.2 ± 1.0 U.R. OD/mg; p<0.05). Moreover, AIA increased MPO in PVAT-t on D43 (15.3 ± 1.3 vs. 38.5 ± 7.5 U.R. OD/mg; p<0.05), whereas this increase began on D29 in PVAT-a (1.9 ± 0.1 vs. 19.5 ± 6.5 U.R. OD/mg; p<0.05). The O 2 •- production has already increased from D15 (98.0 ± 12.1 vs. 205.1 ± 25.7 U.R. OD/mg; p<0.05) in PVAT-t and persisted throughout the evolution of the model. In addition, AIA increased TBARS in both PVAT-t (2.9 ± 1.1 vs. 19.5 ± 7.3 µ M/mg; p<0.05) and PVAT-a (1.5 ± 0.9 vs. 12.4 ± 3.3 µ M/mg; p<0.05) on D36, without changing the TNF- α, IL-1 β or IL-6 production. In PVAT-t, but not in PVAT-a, AIA increased the expression of PGC1a on D15 (0.9 ± 0.32 vs. 3.6 ± 0.7 relative expression), while reduced the expression of ASC-1 from D36 [1.0 ± 0.2 vs. 0.3 ± 0.1 relative expression; p<0.05]. In conclusion, AIA promotes infiltration of inflammatory cells, oxidative stress and browning of PVAT. These changes are more noticeable in the later phase of the model, around the D36. This study was supported by the Coordination for the Improvement of Higher Education Personnel (CAPES) and by the São Paulo Research Foundation (FAPESP - proc.2022/09513-0). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.