Session Type: Poster Session (Monday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Adipocytokines are bioactive factors mainly produced by adipose tissue and exert many important effects on energy homeostasis as well as immune responses. Osteoarthritis (OA) is one of the most common degenerative joint diseases whereas rheumatoid arthritis (RA) is a chronic autoimmune joint disease. To evaluate the role of adipokines and obesity in the setting of both diseases at different time points, we combined an obesity model (high-fat diet, HFD) with a model for OA (DMM, destabilization of the medial meniscus) and RA (collagen induced arthritis, CIA).
Methods: The DMM model was performed in C57Bl/6 mice fed with HFD or ND (normal diet) prior to OA induction. In the CIA model, DBA/1Rj mice were fed with the same diets for 12 (DMM) and 6 (CIA) weeks prior to CIA induction. Mice were sacrificed to collect histological as well as serological data after 4, 6 and 8 weeks (DMM model) or after 4, 5.5 and 7 weeks (CIA model) after arthritis induction. Histological scoring for arthritis induction (both models) and assessment of a clinical score for the CIA model was performed. Serum concentrations of CRP, the adipokines adiponectin, leptin and visfatin were measured. Immunohistochemical stainings were performed to evaluate local adipokine distribution in the joints. Diet-induced systemic changes were analyzed using a fatty liver score and evaluation of crown-like structures (CLS) in adipose tissue.
Results: Induction of OA/ RA was successfully established in an HFD setting, shown by the histological joint destruction and the increased fatty liver score and bodyweight, respectively. In DMM, the number of CLS were significantly higher in the HFD group (0.2 ± 0.16, n=7) compared to the ND group (5.2 ± 0.98, n=8). However, CIA induction increased the number of CLS in HFD (2.77 ± 1.07, n=6) and especially in ND animals (8.14 ± 0.23, n=5) compared to healthy ND mice (0.45 ± 0.03, n=4) and healthy HFD mice (2.57 ± 0.53, n=4) without CIA induction. With regard to healthy animals, CRP serum levels were significantly increased in mice after CIA induction. Interestingly, CIA and DMM induction decreased systemic leptin levels significantly which could not be observed in the local leptin distribution in the joints (CIA).
Conclusion: Our data show that OA is deteriorated by HFD, similar to observations in humans. Histological CIA scoring showed no significant difference in CIA severity under HFD or ND. The high numbers of CLS in CIA animals with ND and the strong reduction of serum leptin levels in CIA animals with HFD indicates that CIA onset and severity are mainly obesity independent while OA (DMM) appears to be influenced by obesity. Interestingly, systemic and local adipokine concentrations did not match in DMM as well as the CIA model. This data suggests a time-dependent adipokine expression and segregation of local and systemic adipokine effects in the context of RA and OA.
To cite this abstract in AMA style:Sauermilch H, Hülser M, Schreiyäck C, Luo Y, Bozec A, Schett G, Müller-Ladner U, Neumann E. Adipocytokines and Obesity in the Context of Rheumatoid and Osteoarthritis Mouse Models [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/adipocytokines-and-obesity-in-the-context-of-rheumatoid-and-osteoarthritis-mouse-models/. Accessed May 30, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/adipocytokines-and-obesity-in-the-context-of-rheumatoid-and-osteoarthritis-mouse-models/