Objective: To determine the point prevalence of painful musculoskeletal (MSK) conditions in obese subjects before and after weight loss following bariatric surgery. Design: Longitudinal, interventional, unblended. Subjects: Forty-eight obese subjects (47 women, one man, mean age 4479 years; mean body mass index (BMI) 5178 kg/m 2 ) recruited from an academic medical center bariatric surgery program. Measurements: Comorbid medical conditions; MSK findings; BMI; Western Ontario McMaster Osteoarthritis Index (WOMAC) for pain, stiffness and function; and SF-36 s for quality of life. Methods: Consecutive subjects were recruited from the University Hospitals of Cleveland Bariatric Surgery Program. Musculoskeletal signs and symptoms and non-MSK comorbid conditions were documented at baseline and at follow-up. Subjects completed the SF-36 s and the WOMAC questionnaires. Analyses were carried out for each MSK site, fibromyalgia syndrome (FMS) and for the cumulative effect on the spine, upper and lower extremities. The impact of change in comorbid medical conditions, BMI, physical and mental health domains of the SF-36 s on the WOMAC pain subscale score was evaluated. SF-36 s outcomes were compared to normal published controls. Results: Forty-eight subjects were available for baseline and a follow-up assessment 6-12 months after gastric bypass surgery. They lost an average of 41715 kg and the mean BMI decreased from 5178 to 3677 kg/m 2 . Baseline comorbid medical conditions were present in 96% before surgery and 23% after weight loss. There was an increased prevalence of painful MSK conditions at baseline compared to general population frequencies. Musculoskeletal complaints had been present in 100% of obese subjects before, and 23% after weight loss. The greatest improvements occurred in the cervical and lumbar spine, the foot and in FMS (decreased by 90, 83, 83 and 92%, respectively). Seventy-nine percent had upper extremity MSK conditions before and 40% after weight loss. Before surgery, 100% had lower extremity MSK conditions and only 37% did after weight loss. The WOMAC subscale and composite scores all improved significantly, as did the SF-36 s . Change in BMI was the main factor impacting the WOMAC pain score. Conclusion: There was a higher frequency of multiple MSK complaints, including non-weight-bearing sites compared to historical controls, before surgery, which decreased significantly at most sites following weight loss and physical activity. These benefits may improve further, as weight loss may continue for up to 24 months. The benefits seen with weight loss indicate that prevention and treatment of obesity can improve MSK health and function.

Objective Little is known regarding the role(s) B cells play in obesity-induced metabolic dysfunction. The present study utilized a mouse with B cell-specific deletion of Id3 (Id3Bcell KO) to identify B cell functions involved in the metabolic consequences of obesity. Approach and Results Diet-induced obese (DIO) Id3Bcell KO mice demonstrated attenuated inflammation and insulin resistance in visceral adipose tissue (VAT), and improved systemic glucose tolerance. VAT in Id3Bcell KO mice had increased B-1b B cells and elevated IgM natural antibodies (Nabs) to oxidation-specific epitopes (OSE). B-1b B cells reduced cytokine production in VAT M1 macrophages, and adoptively transferred B-1b B cells trafficked to VAT and produced NAbs for the duration of thirteen week studies. B-1b B cells null for Id3 demonstrated increased proliferation, established larger populations in Rag1−/− VAT, and attenuated diet-induced glucose intolerance and VAT insulin resistance in Rag1−/− hosts. However, transfer of B-1b B cells unable to secrete IgM had no effect on glucose tolerance. In an obese human population, results provided the first evidence that B-1 cells are enriched in human VAT and IgM antibodies to OSEs inversely correlated with inflammation and insulin resistance. Conclusions Nab-producing B-1b B cells are increased in Id3Bcell KO mice and attenuate adipose tissue inflammation and glucose intolerance in DIO mice. Additional findings are the first to identify VAT as a reservoir for human B-1 cells and to link anti-inflammatory IgM antibodies with reduced inflammation and improved metabolic phenotype in obese humans.

Objective Examine if adding aerobic exercise to standard medical care (EX+SC) prior to bariatric surgery improves metabolic health in relation to surgical outcomes. Methods Fourteen bariatric patients (age: 42.3±2.5y, BMI: 45.1±2.5 kg/m 2) met inclusion criteria and were match-paired to pre-operative SC (n = 7) or EX+SC (n = 7; walking 30min/d, 5d/wk, 65-85% HR peak) for 30d. A 120min mixed meal tolerance test was performed pre-and postintervention (~2d prior to surgery) to assess insulin sensitivity (Matsuda Index) and metabolic flexibility (indirect calorimetry). Aerobic fitness (VO 2 peak), body composition (Bod-Pod), and adipokines (adiponectin, leptin) were also measured. Omental adipose tissue was collected during surgery to quantify gene expression of adiponectin and leptin, and operating time and length of hospital stay were recorded. ANOVA and Cohen's d effect size (ES) was used to test group differences. Results SC tended to increase percent body fat (P = 0.06) after the intervention compared to EX +SC. Although SC and EX+SC tended to raise insulin sensitivity (P = 0.11), EX+SC enhanced metabolic flexibility (P = 0.01, ES = 1.55), reduced total adiponectin (P = 0.01, ES = 1.54) with no change in HMW adiponectin and decreased the length of hospital stay (P = 0.05) compared to SC. Albeit not statistically significant, EX+SC increased VO 2 peak 2.9% compared to a 5.

Roux-en-Y Gastric Bypass remains an excellent and durable operation for long-term weight loss and treatment of obesity-related comorbid disease. Laparoscopic RYGB results in highly favorable outcomes with reduced incisional hernia rates. These 10-year data help to more clearly define long-term outcomes and demonstrate outstanding reduction in comorbid disease following RYGB.

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