Abstract: Background and aims: Obesity is associated with low-grade inflammation in adipose tissue (AT), high lipolytic activity, ectopic fat deposition and insulin-resistance (IR). Bariatric surgery leads to major fat mass loss and improvements in IR and ß-cell function (ß-GS). Aim of this study was to relate the improved metabolic status after Roux-en-Y gastric bypass (RYGB) to the morphological changes of subcutaneous (SAT) and visceral AT (VAT) and skeletal muscle. Materials and methods: 14 non-diabetic (ND) and 14 type 2 diabetic (T2D) obese patients (BMI = 50 ± 2 and 52 ± 2 kg/m2) received a euglycaemic clamp study (to measure IR) with 2H5-glycerol infusion (to measure lipolysis) and a mixed meal test (to measure insulin secretion and ß-GS) before and one year after RYGB. During RYGB, VAT (omental), SAT and rectus abdominis samples were excised for light (LM) and electron microscopy (EM) analysis. Results: Before surgery, both T2D and ND patients showed marked IR and enhanced lipolysis, T2D also had impaired ß-GS. On LM, perivascular and interfibrillar muscle fat content was similar in ND and T2D; intramyocellular fat was more abundant in T2D than ND patients (1.0 [1.5] vs 0.1 [0.5] units, p=0.008). In SAT, adipocyte area and density of crown-like structures (CLS) were similarly increased in T2D and ND. In VAT, adipocyte area (5806 [1793] vs 5056 [1320], p=0.01) and CLS density (3.60 [7.31] vs 0.00 [1.75], p=0.0002) were higher in T2D than ND. ß-GS was inversely related to VAT adipocyte area (r = -0.58, p=0.004) and CLS density (r = -0.50, p=0.02). On EM, SAT and VAT adipocytes showed necrotic material, fibrosis, thickened capillary basal membrane, degenerating adipocytes with thin cytoplasm with extrusion of free lipids in interstitium and small mitochondria. In T2D patients, VAT and SAT blood capillaries contained neutrophils. After RYGB (33% weight loss), IR and lipolysis were markedly improved, equally in ND and T2D (p<0.003 for all). In T2D, ß-GS was improved (p=0.04) but not normalized. By LM, in both ND and T2D fat deposits were reduced in all muscle locations (p<0.03) as were adipocyte area and CLS density in SAT (p<0.0001). By EM, SAT adipocytes were generally smaller, in advanced state of delipidation, with thicker cytoplasm rim and more mitochondria. In T2D, capillaries were free of neutrophils. In the whole dataset, SAT adipocyte area and CLS density were strongly related to BMI, IR and lipolysis (r2’s between 0.40 and 0.81, all p<0.0001). ß-GS was related to SAT CLS density (r = 0.46, p=0.006) and intramyocellular fat (r = 0.53, p=0.001); the post-surgery increase in ß-GS was related to the concomitant decrease in intramyocellular fat (r = -0.79, p=0.002). Conclusion: In morbid obesity, fat accumulation results in adipocyte enlargement, lipid extrusion, macrophage infiltration and cell necrosis. In both T2D and ND, these changes correlate with IR and lipolysis; in VAT, histology is worse in T2D than ND and correlates with ß-cell dysfunction. After surgically-induced major weight loss, AT/muscle histology and IR improve in parallel; in T2D, however, ß-cell glucose sensitivity remains abnormal despite the restoration of tissue morphology, suggesting a different origin for ß-cell incompetence.
Relationship between muscle/adipose tissue morphology, insulin sensitivity and beta cell function in diabetic and nondiabetic obese patients: effects of bariatric surgery
CAMASTRA, STEFANIA;BALDI, SIMONA;FERRANNINI, ELEUTERIO
2014-01-01
Abstract
Abstract: Background and aims: Obesity is associated with low-grade inflammation in adipose tissue (AT), high lipolytic activity, ectopic fat deposition and insulin-resistance (IR). Bariatric surgery leads to major fat mass loss and improvements in IR and ß-cell function (ß-GS). Aim of this study was to relate the improved metabolic status after Roux-en-Y gastric bypass (RYGB) to the morphological changes of subcutaneous (SAT) and visceral AT (VAT) and skeletal muscle. Materials and methods: 14 non-diabetic (ND) and 14 type 2 diabetic (T2D) obese patients (BMI = 50 ± 2 and 52 ± 2 kg/m2) received a euglycaemic clamp study (to measure IR) with 2H5-glycerol infusion (to measure lipolysis) and a mixed meal test (to measure insulin secretion and ß-GS) before and one year after RYGB. During RYGB, VAT (omental), SAT and rectus abdominis samples were excised for light (LM) and electron microscopy (EM) analysis. Results: Before surgery, both T2D and ND patients showed marked IR and enhanced lipolysis, T2D also had impaired ß-GS. On LM, perivascular and interfibrillar muscle fat content was similar in ND and T2D; intramyocellular fat was more abundant in T2D than ND patients (1.0 [1.5] vs 0.1 [0.5] units, p=0.008). In SAT, adipocyte area and density of crown-like structures (CLS) were similarly increased in T2D and ND. In VAT, adipocyte area (5806 [1793] vs 5056 [1320], p=0.01) and CLS density (3.60 [7.31] vs 0.00 [1.75], p=0.0002) were higher in T2D than ND. ß-GS was inversely related to VAT adipocyte area (r = -0.58, p=0.004) and CLS density (r = -0.50, p=0.02). On EM, SAT and VAT adipocytes showed necrotic material, fibrosis, thickened capillary basal membrane, degenerating adipocytes with thin cytoplasm with extrusion of free lipids in interstitium and small mitochondria. In T2D patients, VAT and SAT blood capillaries contained neutrophils. After RYGB (33% weight loss), IR and lipolysis were markedly improved, equally in ND and T2D (p<0.003 for all). In T2D, ß-GS was improved (p=0.04) but not normalized. By LM, in both ND and T2D fat deposits were reduced in all muscle locations (p<0.03) as were adipocyte area and CLS density in SAT (p<0.0001). By EM, SAT adipocytes were generally smaller, in advanced state of delipidation, with thicker cytoplasm rim and more mitochondria. In T2D, capillaries were free of neutrophils. In the whole dataset, SAT adipocyte area and CLS density were strongly related to BMI, IR and lipolysis (r2’s between 0.40 and 0.81, all p<0.0001). ß-GS was related to SAT CLS density (r = 0.46, p=0.006) and intramyocellular fat (r = 0.53, p=0.001); the post-surgery increase in ß-GS was related to the concomitant decrease in intramyocellular fat (r = -0.79, p=0.002). Conclusion: In morbid obesity, fat accumulation results in adipocyte enlargement, lipid extrusion, macrophage infiltration and cell necrosis. In both T2D and ND, these changes correlate with IR and lipolysis; in VAT, histology is worse in T2D than ND and correlates with ß-cell dysfunction. After surgically-induced major weight loss, AT/muscle histology and IR improve in parallel; in T2D, however, ß-cell glucose sensitivity remains abnormal despite the restoration of tissue morphology, suggesting a different origin for ß-cell incompetence.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
