I Arias de la Rosa1, A Escudero-Contreras1, S Rodríguez-Cuenca2, M Ruiz-Ponce1, Y Jiménez-Gómez1, P Ruiz-Limón1, C Pérez-Sánchez1, M C Ábalos-Aguilera1, I Cecchi1,3, R Ortega1, J Calvo1, R Guzmán-Ruiz4,5, M M Malagón4,5, E Collantes-Estevez1, A Vidal-Puig2, Ch López-Pedrera1, N Barbarroja1,5. 1. Rheumatology Service, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain. 2. Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbroke's Hospital, University of Cambridge, Cambridge, UK. 3. Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy. 4. Department of Cell Biology, Physiology and Immunology, IMIBIC, Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain. 5. CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
Abstract
BACKGROUND: Rheumatoid arthritis (RA) patients are at increased risk of insulin resistance (IR); however, the specific mechanisms mediating this association are currently unknown. OBJECTIVE: To investigate whether the inflammatory activity associated with RA accounts for the observed defective glucose metabolism and lipid metabolism in these patients. METHODS: We followed two main strategies: (i) extensive metabolic profiling of a RA cohort of 100 patients and 50 healthy control subjects and (ii) mechanistic studies carried out in both a collagen-induced arthritis mouse model and 3T3-L1 adipocytes treated with conditioned serum from RA patients. RESULTS: Following the exclusion of obese and diabetic subjects, data from RA patients demonstrated a strong link between the degree of systemic inflammation and the development of IR. These results were strengthened by the observation that induction of arthritis in mice resulted in a global inflammatory state characterized by defective carbohydrate and lipid metabolism in different tissues. Adipose tissue was most susceptible to the RA-induced metabolic alterations. These metabolic effects were confirmed in adipocytes treated with serum from RA patients. CONCLUSIONS: Our results show that the metabolic disturbances associated with RA depend on the degree of inflammation and identify inflammation of adipose tissue as the initial target leading to IR and the associated molecular disorders of carbohydrate and lipid homeostasis. Thus, we anticipate that therapeutic strategies based on tighter control of inflammation and flares could provide promising approaches to normalize and/or prevent metabolic alterations associated with RA.
BACKGROUND:Rheumatoid arthritis (RA) patients are at increased risk of insulin resistance (IR); however, the specific mechanisms mediating this association are currently unknown. OBJECTIVE: To investigate whether the inflammatory activity associated with RA accounts for the observed defective glucose metabolism and lipid metabolism in these patients. METHODS: We followed two main strategies: (i) extensive metabolic profiling of a RA cohort of 100 patients and 50 healthy control subjects and (ii) mechanistic studies carried out in both a collagen-induced arthritismouse model and 3T3-L1 adipocytes treated with conditioned serum from RA patients. RESULTS: Following the exclusion of obese and diabetic subjects, data from RA patients demonstrated a strong link between the degree of systemic inflammation and the development of IR. These results were strengthened by the observation that induction of arthritis in mice resulted in a global inflammatory state characterized by defective carbohydrate and lipid metabolism in different tissues. Adipose tissue was most susceptible to the RA-induced metabolic alterations. These metabolic effects were confirmed in adipocytes treated with serum from RA patients. CONCLUSIONS: Our results show that the metabolic disturbances associated with RA depend on the degree of inflammation and identify inflammation of adipose tissue as the initial target leading to IR and the associated molecular disorders of carbohydrate and lipid homeostasis. Thus, we anticipate that therapeutic strategies based on tighter control of inflammation and flares could provide promising approaches to normalize and/or prevent metabolic alterations associated with RA.
Authors: Nuria Casanova-Vallve; Dumitru Constantin-Teodosiu; Andrew Filer; Rowan S Hardy; Paul L Greenhaff; Victoria Chapman Journal: PLoS One Date: 2020-07-07 Impact factor: 3.240
Authors: Iván Arias de la Rosa; Alejandro Escudero-Contreras; Miriam Ruiz-Ponce; Cristóbal Román-Rodríguez; Carlos Pérez-Sánchez; María Del Carmen Ábalos-Aguilera; Rafaela Ortega-Castro; Juan Alcaide; Mora Murri; Pilar Font; Jerusalem Calvo-Gutiérrez; Maria Luque-Tevar; Alejandra Maria Patiño-Trives; Rocío Guzmán-Ruiz; Maria Del Mar Malagón; Francisco José Tinahones; Eduardo Collantes-Estévez; Chary López-Pedrera; Nuria Barbarroja Journal: Front Immunol Date: 2021-10-13 Impact factor: 7.561