Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Rheumatoid arthritis (RA) patients are at higher risk for insulin resistance (IR). The association between RA and IR, and its role on the different characteristics of the disease, such as duration and activity have not been well defined. In addition, there is a gap of knowledge regarding the link between systemic/local inflammation and insulin sensitivity and lipid metabolism in RA patients.Objective: To explore the effects of the inflammation on the glucose and lipid metabolism in the RA context, following three strategies: RA patients, collagen induced arthritis (CIA) mouse model and in vitro treatment of 3T3L1 adipocytes.
Methods: Human study: 150 RA patients and 40 healthy donors were included. IR was quantified using the homeostatic model assessment of IR (HOMA-IR). Mouse model: 20 CB57J/BL mice were used; 5 mice were used as non-diseased group, and 15 were used in CIA modelling: sorted in low and high activity of the disease based on the number of inflamed digits depending on the duration of the disease. Plasma, leukocytes, skeletal muscle, liver and adipose tissue were collected. Treatment of adipocytes with serum from RA patients: 3T3L1 adipocytes were treated with serum 10% of RA patients and healthy donors for 24h. The expression of genes and proteins involved in inflammation, lipid metabolism and insulin signalling was analysed in all the tissues and cells.
Results: Percentages of obesity, hypertension, atherogenic risk, metabolic syndrome and IR were significantly increased in the RA group. Although mean time of evolution was 7 years, no association between IR and the duration of the disease was found. Levels of HOMA-IR significantly correlated with DAS28 and C-reactive protein levels, suggesting a link between the degree of systemic inflammation and the development of IR in these patients. These results were strengthened by observing that the induction of arthritis in mice resulted in a global inflammatory state characterized by defective carbohydrate and lipid metabolism in leukocytes, liver, muscle and adipose tissue, consistent with defects in insulin signaling. Adipose tissue was the organ most susceptible to the RA-induced metabolic alterations, which were observed from early stages of the disease. These metabolic effects were recapitulated in 3T3-L1 adipocytes treated with serum from RA patients.
Conclusion: 1) IR was closely associated with an increase in disease activity and systemic inflammation in RA patients. 2) Induction of arthritis in mice promoted an increase in inflammation in skeletal muscle, adipose tissue and leukocytes, accompanied by alterations in metabolic pathways favouring the development of insulin resistance on these tissues. 3) The inflammatory mediators in RA are the direct responsible for the metabolic alterations observed in adipose tissue. Altogether, our results show the direct effect of RA-associated chronic inflammation mediating the alterations occurred in glucose and lipid metabolism associated with this disorder. Thus, therapeutic strategies aimed to inhibit inflammation targeting proinflammatory cytokines might be an excellent option to normalize the metabolic alterations associated with RA. Funded by ISCIII-FIS (CP15/00158)
To cite this abstract in AMA style:Barbarroja N, Arias de la Rosa I, Rodriguez-Cuenca S, Jiménez-Gómez Y, Ruiz-Limon P, Perez-Sanchez C, Abalos-Aguilera MC, Cecchi I, Ortega-Castro R, Calvo-Gutierrez J, Guzman-Ruiz R, Malagon MDM, Collantes-Estévez E, Vidal-Puig A, Escudero-Contreras A, Lopez-Pedrera C. Defective Glucose and Lipid Metabolism in Rheumatoid Arthritis Is Determined By Chronic Inflammation in Metabolic Tissues [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/defective-glucose-and-lipid-metabolism-in-rheumatoid-arthritis-is-determined-by-chronic-inflammation-in-metabolic-tissues/. Accessed January 25, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/defective-glucose-and-lipid-metabolism-in-rheumatoid-arthritis-is-determined-by-chronic-inflammation-in-metabolic-tissues/