leptin and Synovitis

To examine whether a weight loss intervention programme improves RA disease activity and/or musculoskeletal ultrasound synovitis measures in obese RA patients.. We conducted a proof-of-concept, 12-week, single-blind, randomized controlled trial of obese RA patients (BMI ≥ 30) with 28-joint DAS (DAS28)  ≥ 3.2 and with evidence of power Doppler synovitis. Forty patients were randomized to the diet intervention (n = 20) or control group (n = 20). Diet intervention consisted of a hypocaloric diet of 1000-1500 kcal/day and high protein meal replacements. Co-primary outcomes included change in DAS28 and power Doppler ultrasound (PDUS)-34. Clinical disease activity, imaging, biomarkers, adipokines and patient-reported outcomes were monitored throughout the trial. Recruitment terminated early. All analyses were based on intent-to-treat for a significance level of 0.05.. The diet intervention group lost an average 9.5 kg/patient, while the control group lost 0.5 kg (P < 0.001). Routine Assessment of Patient Index Data 3 (RAPID3) improved, serum leptin decreased and serum adiponectin increased significantly within the diet group and between the groups (all P < 0.03). DAS28 decreased, 5.2 to 4.2, within the diet group (P < 0.001; -0.51 [95% CI -1.01, 0.00], P = 0.056, between groups). HAQ-Disability Index (HAQ-DI) improved significantly within the diet group (P < 0.04; P = 0.065 between group). Ultrasound measures and the multi-biomarker disease activity score did not differ between groups (PDUS-34 -2.0 [95% CI -7.00, 3.1], P = 0.46 between groups).. Obese RA patients on the diet intervention achieved weight loss. There were significant between group improvements for RAPID3, adiponectin and leptin levels, and positive trends for DAS28 and HAQ-DI. Longer-term, larger weight loss studies are needed to validate these findings, and will allow for further investigative work to improve the clinical management of obese RA patients.. ClinicalTrials.gov, https://clinicaltrials.gov, NCT02881307.

Topics: Adiponectin; Antirheumatic Agents; Arthritis, Rheumatoid; Biomarkers; Diet, Reducing; Humans; Leptin; Obesity; Severity of Illness Index; Single-Blind Method; Synovitis

The mechanisms linking obesity and osteoarthritis (OA) are not fully understood and have been generally attributed to increased weight, rather than metabolic or inflammatory factors. Here, we examined the influence of fatty acids, adipokines, and body weight on OA following joint injury in an obese mouse model.. Mice were fed high-fat diets rich in various fatty acids (FA) including saturated FAs (SFAs), ω-6 polyunsaturated FAs (PUFAs), and ω-3 PUFAs. OA was induced by destabilising the medial meniscus. Wound healing was evaluated using an ear punch. OA, synovitis and wound healing were determined histologically, while bone changes were measured using microCT. Activity levels and serum cytokines were measured at various time-points. Multivariate models were performed to elucidate the associations of dietary, metabolic and mechanical factors with OA and wound healing.. Using weight-matched mice and multivariate models, we found that OA was significantly associated with dietary fatty acid content and serum adipokine levels, but not with body weight. Furthermore, spontaneous activity of the mice was independent of OA development. Small amounts of ω-3 PUFAs (8% by kcal) in a high-fat diet were sufficient to mitigate injury-induced OA, decreasing leptin and resistin levels. ω-3 PUFAs significantly enhanced wound repair, SFAs or ω-6 PUFAs independently increased OA severity, heterotopic ossification and scar tissue formation.. Our results indicate that with obesity, dietary FA content regulates wound healing and OA severity following joint injury, independent of body weight, supporting the need for further studies of dietary FA supplements as a potential therapeutic approach for OA.

Topics: Animals; Body Weight; Bone and Bones; Diet, High-Fat; Dietary Fats; Disease Models, Animal; Ear Auricle; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Femur; Leg Injuries; Leptin; Mice; Obesity; Osteoarthritis; Osteoarthritis, Knee; Resistin; Stifle; Synovitis; Tibia; Tibial Meniscus Injuries; Wound Healing; X-Ray Microtomography

Reports suggest leptin, which was initially described as a hormone that regulates food intake and energy balance, has an intimate relationship, and interacts with the immune system. Leptin consumption in the synovial cavity in patients with rheumatoid arthritis (RA) reported to have protective effect against erosion. To determine the difference in serum leptin and synovial/serum leptin ratio between RA and control and to assess whether these parameters correlate with systemic inflammation in RA. Also, the hypothesis that synovial/serum leptin ratio could be linked to joint erosion in RA was evaluated. The study subjects consisted of 40 consecutive patients with RA, 30 patients of them had knee effusion, and 30 controls. Ten of these controls had acute knee injury and their synovial fluid was obtained for comparison of synovial/serum leptin ratio with patients with RA. The mean serum leptin in patients with RA was significantly higher than controls. Also, the synovial leptin and synovial/serum leptin ratio in the RA patients with effusion was significantly higher than in the 10 control subjects with traumatic effusion. Serum leptin in the 30 RA patients with effusion was higher than the matched synovial leptin. In RA patients with effusion, synovial/serum leptin ratio was also significantly higher in RA patients with erosion than RA patients without erosion. Serum leptin level and synovial/serum leptin ratio are significantly correlated with the RA duration, DAS28, ESR, CRP, TNF-α, and IL-6. Finally, in regression analysis, only the synovial/serum leptin ratio was positively associated with erosion in patients with RA. In RA, there is a significant increase in circulating leptin levels and synovial/serum leptin ratio compared to non-RA controls. Serum leptin and synovial/serum leptin ratio are significantly in erosive RA than non-erosive RA. Both parameters are correlated with disease duration and parameters of RA activity. In regression analysis, only the synovial/serum leptin ratio was positively associated with erosion in patients with RA. These results indicate that local consumption of leptin in the joint cavity has a protective role against the destructive course of RA.

Topics: Adult; Arthritis, Rheumatoid; Exudates and Transudates; Female; Humans; Joints; Leptin; Male; Prospective Studies; Synovitis; Young Adult