Key result
Roux-en-Y bariatric surgery significantly reduced BMI and improved clinical metabolic features at 12 years compared to non-surgical obesity, but most hepatokine, adipokine, and myokine markers did not normalize to normal-weight levels.
Why the study?
It was unknown whether underlying homeostatic metabolic processes involving hepatokines, adipokines, and myokines normalize after Roux-en-Y bariatric surgery.
Does Roux-en-Y gastric bypass surgery normalize metabolic homeostasis markers (hepatokines, adipokines, myokines) in subjects with severe obesity and type 2 diabetes at 12 years compared to non-surgical obese and normal-weight cohorts?
Cross-Sectional (n=165)
No
Does Roux-en-Y gastric bypass surgery normalize metabolic homeostasis markers (hepatokines, adipokines, myokines) in subjects with severe obesity and type 2 diabetes at 12 years compared to non-surgical obese and normal-weight cohorts?
While bariatric surgery induces significant long-term weight loss and clinical improvement, it does not completely normalize underlying metabolic homeostasis markers (hepatokines, adipokines, myokines) to lean levels, likely because patients remain in class-1 obesity.
Answers are grounded in this paper and cite their sources.
Persistent organokine dysregulation post-bariatric surgery despite clinical gains; leaves open whether targeted interventions are needed.
Background A 12-year study comparing clinical outcomes following Roux-en-Y bariatric surgery showed long-term weight loss with remission/prevention of type-2-diabetes (T2D), hypertension and dyslipidemia. However, it is unknown whether the underlying homeostatic metabolic processes involving hepatokines, adipokines and myokines also normalize. Using this 12-year study, we determined whether metabolic indices improved in post-surgical (BMI:34.4kg/m 2 ) versus non-surgical comparator-subjects-with-obesity (BMI:43.8kg/m 2 ) at 12-year follow-up (both cohorts with baseline diabetes), and if post-surgical subjects normalized their metabolic processes to those of a normal-weight cohort without diabetes. Methods Cross-sectional design. Plasma from a cohort of Roux-en-Y bariatric surgery (n=50) and non-surgery (n=76) comparator-subjects-with-obesity (both cohorts at 12-year follow-up) plus a normal-weight cohort (n=39) was assayed by Luminex immunoassay or ELISA for hepatokines [angiopoietin-like proteins-(ANGPTL3; ANGPTL4; ANGPTL6); fibroblast growth factors-(FGF19; FGF21; FGF23)]; adipokines [adipsin; adiponectin; FGF19] and myonectin. Results After age and gender adjustment, surgery versus comparator-subjects-with-obesity had lower BMI (34.4 ± 1.0 vs 43.8 ± 0.9kg/m 2 ; p<0.0001), HbA1c (6.2 ± 0.3 vs 7.7 ± 0.2%; p<0.0001), insulin resistance (HOMA-IR, 2.0 ± 1.5 vs 10.8 ± 1.4; p<0.0001) fat mass (45.6 ± 2.2 vs 60.0 ± 2.0; p<0.0001), HDL-C (55.4 ± 2.6 vs 42.6 ± 2.3mg/dL; p<0.0001), triglycerides (130 ± 14 vs 187 ± 12mg/dL; p<0.0001) and higher adiponectin (25.9 ± 2.3 vs 15.7 ± 2.0µg/ml; p<0.001); Adipsin, ANGPTL3, ANGPTL4, ANGPTL6, FGF19, FGF21, FGF23 and myonectin did not differ. Surgery versus normal-weight group: higher ANGPTL4 (156 ± 6 vs 119 ± 7ng/mL; p<0.0001), higher FGF23 (96.4 ± 10.1 vs 50.9 ± 11.5pg/mL; p=0.007) and lower myonectin (744 ± 55 vs 969 ± 66ng/mL; p=0.002); adiponectin, adipsin ANGPTL3, ANGPTL6, FGF19, FGF21 did not differ. Non-surgery comparator-subjects-with-obesity versus normal-weight group: higher adipsin (1859 ± 94 vs 1314 ± 133ng/mL; p=0.0001), higher FGF23 (84.6 ± 8.5 vs 50.9 ± 11.5pg/mL; p<0.0001) and higher ANGPTL4 (171 ± 5 vs 119 ± 7ng/mL; p<0.0001); adiponectin ANGPTL3, ANGPTL6, FGF19, FGF21 and myonectin did not differ. Conclusion Bariatric surgery markedly improved anthropometric and metabolic features versus comparator-subjects-with-obesity at 12-year follow-up, indicating benefit of weight loss. However, despite weight loss, these patients still had class-1 obesity, as reflected in the adipokine, hepatokine and myokine markers of body homeostasis that did not completely normalize to indicative values of normal-weight subjects, suggesting either that this is the new normal for these patients or that weight loss to a BMI<25kg/m 2 is needed for normalization of these parameters.
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Butler et al. (2023) conducted a cross-sectional in Obesity and Type 2 Diabetes (n=165). Roux-en-Y bariatric surgery vs. Non-surgical comparator subjects with obesity was evaluated on Body Mass Index (BMI) (MD -9.4, p=<0.0001). Roux-en-Y bariatric surgery significantly reduced BMI and improved clinical metabolic features at 12 years compared to non-surgical obesity, but most hepatokine, adipokine, and myokine markers did not normalize to normal-weight levels.
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