Early Changes in Adipose Tissue Morphology, Gene Expression, and Metabolism After RYGB in Patients With Obesity and
Petros Katsogiannos1, Prasad G Kamble1, Gretha J Boersma1
1Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Context:
Roux-en-Y gastric bypass (RYGB) surgery effectively prevents or treats type 2 diabetes (T2D). Adipose tissue (AT) mechanisms may be of importance.
Objective:
To assess the relationship between early changes in whole-body and AT metabolism in surgically treated patients with T2D.
Design And Setting:
A randomized single-center study.
Patients:
Nineteen patients with T2D with body mass index 30 to 45 kg/m2.
Interventions:
Thirteen patients were assessed at baseline and 4 and 24 weeks after RYGB (preceded by a 4-week low-calorie diet) and compared with 6 control patients continuing standard medical treatment: oral glucose tolerance test, subcutaneous AT biopsies for gene expression, adipocyte size, glucose uptake, lipolysis, and insulin action.
Results:
At 4 and 24 weeks post-RYGB, all patients but one had stopped diabetes medication. Fasting glucose, HbA1c, and insulin levels decreased and the Matsuda index increased compared with baseline (P < 0.01 for all), indicating improved whole-body insulin sensitivity. Mean adipocyte size significantly reduced, more at 4 than at 24 weeks; at 4 weeks, glucose uptake per adipocyte was lowered, and isoproterenol-stimulated lipolysis tended to increase, whereas the fold insulin effects on glucose uptake and lipolysis were unchanged. Expression of genes involved in fatty acid oxidation, CPT1b and adiponectin, was increased at 4 weeks, whereas leptin and E2F1 (involved in cell proliferation) were reduced (P < 0.05 for all).
Conclusion:
Glycemic control and in vivo insulin sensitivity improved 4 weeks after RYGB, but adipocyte insulin sensitivity did not change despite a marked reduction in adipocyte size. Thus, mechanisms for a rapid improvement of T2D after RYGB may occur mainly in other tissues than adipose.
Insights
Roux-en-Y gastric bypass (RYGB) rapidly improves type 2 diabetes (T2D) and insulin sensitivity. However, adipose tissue (AT) insulin sensitivity remains unchanged, suggesting other mechanisms drive T2D remission after RYGB.
Area of Science:
- Metabolic Surgery
- Endocrinology
- Type 2 Diabetes Research
Background:
- Roux-en-Y gastric bypass (RYGB) is effective for type 2 diabetes (T2D) treatment.
- Adipose tissue (AT) plays a role in T2D, but its specific mechanisms post-RYGB are unclear.
Purpose of the Study:
- To investigate early changes in whole-body and AT metabolism following RYGB in T2D patients.
- To assess the impact of RYGB on insulin sensitivity and AT function.
Main Methods:
- A randomized controlled trial comparing RYGB with standard medical treatment.
- Evaluated 19 T2D patients (BMI 30-45 kg/m²) undergoing RYGB and 6 controls.
- Assessed oral glucose tolerance, AT biopsies (gene expression, adipocyte size, glucose uptake, lipolysis), and insulin action at baseline, 4, and 24 weeks post-surgery.
Main Results:
- RYGB patients showed significant improvements in glycemic control (fasting glucose, HbA1c) and insulin sensitivity (Matsuda index) by 4 weeks.
- Adipocyte size decreased significantly post-RYGB, but adipocyte insulin sensitivity and insulin's effects on glucose uptake/lipolysis remained unchanged.
- Gene expression in AT shifted towards increased fatty acid oxidation and decreased cell proliferation markers.
Conclusions:
- RYGB rapidly improves glycemic control and whole-body insulin sensitivity within 4 weeks.
- Despite reduced adipocyte size, AT insulin sensitivity did not improve, indicating non-adipose tissue mechanisms are key for rapid T2D remission post-RYGB.
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