Saturated fatty acids intake is associated with muscle atrophy in rheumatoid arthritis

Abstract

Abstract Background Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by joint inflammation, abnormal body composition, and an increased risk for sarcopenia. Muscle wasting in turn increases the risk of infection, morbidity, and premature mortality, but little is known of the relation between nutrient intake and sarcopenia in RA. Methods A prospective cohort study with follow‐up for 1 year examined body composition and diet in female outpatients with RA. We performed logistic regression analysis to assess which factors might have contributed to this loss of muscle mass. Multivariate logistic regression analysis with a forward–backward stepwise selection was also analysed. SKG/Jcl mice, which develop RA spontaneously, were fed normal chow or a high‐fat diet (HFD) and evaluated for inflammation and muscle mass. Results A total 53 female patients were included. The median age was 57.0 years, with an interquartile range (IQR) of 49.5 to 62.0 years, and the median disease duration was 4.0 years, with an IQR of 2.0 to 9.0 years. Fourteen patients (26.4%) had skeletal muscle mass index below the cut‐off for sarcopenia (≤5.7 kg/m2) as defined by the Asia Working Group for Sarcopenia. Multiple logistic regression analysis revealed that the intake of saturated fatty acids was associated with a >5% decrease in skeletal muscle index of RA patients over 1 year [odds ratio 95% confidence interval 1.431 (1.082–1.894), P = 0.012]. In 9 weeks old SKG/Jcl mice, HFD feeding precipitated the onset of RA and exacerbated rheumatoid synovitis in association with the induction of T helper 17 cell differentiation. The serum concentrations of inflammatory cytokines including IL‐6 and TNF‐α were significantly higher in HFD‐fed RA mice than in normal chow (NC)‐fed RA mice or in HFD‐fed control mice (IL‐6; 3.8 vs. 32.2 pg/mL, P < 0.05). Moreover, the HFD increased expression of the genes for the ubiquitin ligases atrogin‐1 and muscle‐specific RING‐finger protein‐1 (MuRF‐1) in skeletal muscle and elicited a marked loss of muscle mass in these mice (atrogin‐1; 1.72‐fold, MuRF‐1; 1.24‐fold in HFD‐fed mice). HFD‐fed RA mice showed a significant decrease in the weight of gastrocnemius and extensor digitorum longus and muscle volume of the lower limbs compared with NC‐fed RA mice or HFD‐fed control mice at 14 weeks of age. Conclusions Our findings suggest that the consumption of saturated fat may be related to muscle loss in RA patients, and they may therefore provide a basis for a new dietary intervention strategy to prevent muscle wasting associated with this disease.

Keywords

• Rheumatoid arthritis
• Saturated fatty acids
• Sarcopenia
• T helper 17 cell