RESUMEN
KEY POINTS: Hepatic insulin resistance in patients with obesity or type 2 diabetes has been suggested to result from hepatic mitochondrial dysfunction. High-resolution respirometry (HRR) can be used to assess oxidative phosphorylation by measuring the mitochondrial oxygen consumption rate in the individual complexes of the mitochondria. By using HRR, the present study demonstrates no difference in hepatic mitochondrial oxidative phosphorylation among subjects with obesity with or without type 2 diabetes and non-obese controls. Furthermore, the amount of mitochondria, assessed by the citrate synthase activity, is not different between the three groups. Together the present findings indicate that hepatic mitochondrial oxidative phosphorylation capacity is not impaired in patients with obesity or type 2 diabetes. ABSTRACT: Obese patients with type 2 diabetes (T2DM) and without type 2 diabetes (OB) are characterized by high hepatic lipid content and hepatic insulin resistance. This may be linked to impaired hepatic mitochondrial oxidative phosphorylation (OXPHOS) capacity. The aim of the present study was to investigate and compare hepatic mitochondrial OXPHOS capacity in T2DM, OB and non-obese controls (CON). Seventeen obese patients (nine OB and eight T2DM) and six CON patients had perioperative liver biopsies taken. Samples were divided into three parts to measure (1) complex I, II and IV linked respiration, (2) citrate synthase (CS) activity and (3) lipid droplet (LD) size and area (% of total tissue area filled by LDs). State 3 respiration of complex I, II and IV and the CS activity did not differ in OB, T2DM and CON. LD size was significantly higher in T2DM compared with CON, and LD area tended (P = 0.10) to be higher in T2DM and OB compared with CON. The present findings indicate that hepatic OXPHOS capacity is not different in patients with markedly different weight and glycaemic control. Furthermore, the results do not support impaired hepatic mitochondrial respiratory capacity playing a major role in the development of obesity-induced type 2 diabetes.
Asunto(s)
Hígado/metabolismo , Mitocondrias Hepáticas/metabolismo , Obesidad/metabolismo , Fosforilación Oxidativa , Adulto , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana EdadRESUMEN
The majority of the patients with type 2 diabetes (T2DM) show remission after Roux-en-Y gastric bypass (RYGB). This is the result of increased postoperative insulin sensitivity and ß-cell secretion. The aim of the present study was to elucidate the importance of the preoperative ß-cell function in T2DM for the chance of remission after RYGB. Fifteen patients with and 18 without T2DM had 25 g oral (OGTT) and intravenous (IVGTT) glucose tolerance tests performed at inclusion, after a diet-induced weight loss, and 4 and 18 months after RYGB. Postoperative first phase insulin secretion rate (ISR) during the IVGTT and ß-cell glucose sensitivity during the OGTT increased in T2DM. Postoperative insulin sensitivity and the disposition index (DI) markedly increased in both groups. By stratifying the T2DM into two groups according to highest (T2DMhigh ) and lowest (T2DMlow ) baseline DI, a restoration of first phase ISR and ß-cell glucose sensitivity were seen only in T2DMhigh . Remission of type 2 diabetes was 71 and 38% in T2DMhigh and T2DMlow , respectively. Postoperative postprandial GLP-1 concentrations increased markedly, but did not differ between the groups. Our findings emphasize the importance of the preoperative of ß-cell function for remission of diabetes after RYGB.
Asunto(s)
Anastomosis en-Y de Roux/efectos adversos , Diabetes Mellitus Tipo 2/fisiopatología , Células Secretoras de Insulina/metabolismo , Obesidad/fisiopatología , Adulto , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/cirugía , Femenino , Péptido 1 Similar al Glucagón/metabolismo , Humanos , Insulina/metabolismo , Secreción de Insulina , Células Secretoras de Insulina/fisiología , Masculino , Obesidad/cirugía , Periodo PreoperatorioRESUMEN
Adipose tissue exerts important endocrine and metabolic functions in health and disease. Yet the bioenergetics of this tissue is not characterized in humans and possible regional differences are not elucidated. Using high resolution respirometry, mitochondrial respiration was quantified in human abdominal subcutaneous and intra-abdominal visceral (omentum majus) adipose tissue from biopsies obtained in 20 obese patients undergoing bariatric surgery. Mitochondrial DNA (mtDNA) and genomic DNA (gDNA) were determined by the PCR technique for estimation of mitochondrial density. Adipose tissue samples were permeabilized and respirometric measurements were performed in duplicate at 37 degrees C. Substrates (glutamate (G) + malate (M) + octanoyl carnitine (O) + succinate (S)) were added sequentially to provide electrons to complex I + II. ADP ((D)) for state 3 respiration was added after GM. Uncoupled respiration was measured after addition of FCCP. Visceral fat contained more mitochondria per milligram of tissue than subcutaneous fat, but the cells were smaller. Robust, stable oxygen fluxes were found in both tissues, and coupled state 3 (GMOS(D)) and uncoupled respiration were significantly (P < 0.05) higher in visceral (0.95 +/- 0.05 and 1.15 +/- 0.06 pmol O(2) s(1) mg(1), respectively) compared with subcutaneous (0.76 +/- 0.04 and 0.98 +/- 0.05 pmol O(2) s(1) mg(1), respectively) adipose tissue. Expressed per mtDNA, visceral adipose tissue had significantly (P < 0.05) lower mitochondrial respiration. Substrate control ratios were higher and uncoupling control ratio lower (P < 0.05) in visceral compared with subcutaneous adipose tissue. We conclude that visceral fat is bioenergetically more active and more sensitive to mitochondrial substrate supply than subcutaneous fat. Oxidative phosphorylation has a higher relative activity in visceral compared with subcutaneous adipose tissue.
Asunto(s)
Respiración de la Célula , Metabolismo Energético , Grasa Intraabdominal/metabolismo , Mitocondrias/metabolismo , Obesidad Mórbida/metabolismo , Grasa Subcutánea Abdominal/metabolismo , Adulto , Biopsia , Carbonil Cianuro p-Trifluorometoxifenil Hidrazona/farmacología , Carnitina/análogos & derivados , Carnitina/metabolismo , Respiración de la Célula/efectos de los fármacos , ADN Mitocondrial/metabolismo , Metabolismo Energético/efectos de los fármacos , Femenino , Ácido Glutámico/metabolismo , Humanos , Grasa Intraabdominal/efectos de los fármacos , Grasa Intraabdominal/ultraestructura , Malatos/metabolismo , Masculino , Microscopía Electrónica de Transmisión , Mitocondrias/efectos de los fármacos , Obesidad Mórbida/patología , Epiplón , Fosforilación Oxidativa , Grasa Subcutánea Abdominal/efectos de los fármacos , Grasa Subcutánea Abdominal/ultraestructura , Ácido Succínico/metabolismo , Factores de Tiempo , Desacopladores/farmacologíaRESUMEN
A 50-year-old woman was admitted with abdominal pain, vomiting, fever and diarrhoea. She had increased white blood cell count and increased level of liver enzymes. A CT scan revealed 13 abscesses in the liver and tests showed Streptococcus angin-osus. Investigation showed no entry point for bacteria. The woman underwent laparoscopic investigation, and the absces-ses were completely drained preoperatively without installation of catheter in spite of large abscess formations. After 26 days of admittance with antibiotic treatment she was discharged and check-up revealed no re-formation of the abscesses.
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Drenaje/métodos , Laparoscopía/métodos , Absceso Piógeno Hepático/terapia , Femenino , Humanos , Absceso Piógeno Hepático/diagnóstico por imagen , Absceso Piógeno Hepático/microbiología , Persona de Mediana Edad , Streptococcus anginosus/aislamiento & purificación , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To examine 24-h blood pressure (24BP), systemic haemodynamics and the effect of sodium intake on 24BP in obese patients before and after gastric bypass surgery [laparoscopic Roux-en-Y gastric bypass (LRYGB)], and to determine whether weight loss from LRYGB might be related to an increase in plasma concentrations of atrial natriuretic peptide. METHODS: Twelve hypertensive and 12 normotensive morbidly obese patients underwent LRYGB: 24BP, systemic haemodynamics and mid-regional pro-atrial natriuretic peptide (MRproANP) were assessed before, 6 weeks and 12 months after surgery. The effect of high versus low sodium intake on 24BP was evaluated before and 12 months after LRYGB. RESULTS: Six weeks after LRYGB, the average weight loss was 20âkg, with a further 21âkg weight loss 1 year after surgery. In hypertensive patients, 24BP was significantly reduced at 6 weeks, but not 1 year after LRYGB. However, antihypertensive medications were successively reduced from baseline to 1 year after surgery. In normotensive patients, there was no change in 24BP 6 weeks after LRYGB, but a tendency towards a reduction 1 year after the operation. Plasma concentrations of MRproANP were subnormal prior to surgery in hypertensive patients and increased by 77% 1 year after the operation. In normotensive patients, preoperative concentrations were normal and increased only by 6%. High sodium intake induced plasma volume expansion, increased stroke volume and cardiac output, but no significant change in 24BP - neither before nor after LRYGB. CONCLUSIONS: LRYGB resulted in a significant 24BP reduction and a substantial increase in MRproANP plasma concentrations in hypertensive, obese patients 6 weeks after surgery, suggesting a causal link between obesity-hypertension and altered release/degradation of cardiac natriuretic peptides.
Asunto(s)
Factor Natriurético Atrial/metabolismo , Derivación Gástrica , Hipertensión/cirugía , Obesidad Mórbida/cirugía , Adulto , Factor Natriurético Atrial/sangre , Presión Sanguínea , Femenino , Humanos , Hipertensión/epidemiología , Laparoscopía , Masculino , Persona de Mediana Edad , Obesidad Mórbida/epidemiología , Factores de Tiempo , Pérdida de PesoRESUMEN
Morbid obesity in teenagers has become an increasing problem. Conventional diet has not yet shown effective long-term weight loss. Alternatively, bariatric surgery on adolescents has resulted in substantial weight loss, recovery from diabetes, improvement of cardiovascular risk factors and improvement in psychosocial status. Still, surgery performed on adolescents provides ethical challenges such as the unknown long-term prognosis after surgery. Despite these challenges, in cases of severe intractable obesity or development of life-threatening complications due to obesity, surgery should be considered.
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Cirugía Bariátrica , Obesidad Infantil/cirugía , Adolescente , Cirugía Bariátrica/efectos adversos , Cirugía Bariátrica/psicología , Índice de Masa Corporal , Niño , Diabetes Mellitus/sangre , Intolerancia a la Glucosa/sangre , Humanos , Obesidad Mórbida/psicología , Obesidad Mórbida/cirugía , Obesidad Infantil/psicología , Complicaciones Posoperatorias , Calidad de VidaRESUMEN
BACKGROUND: The specific mechanisms behind weight loss and comorbidity improvements in obese patients after Roux-en-Y gastric bypass (RYGBP) are still poorly understood. The aim of this study was to establish and evaluate the feasibility of a long-term survival RYGBP model in super obese Göttingen minipigs in order to improve the translational potential relative to current animal models. METHODS: Eleven Göttingen minipigs with diet-induced obesity underwent laparoscopic RYGBP and were followed up to 9 months after surgery. Intra- and post-operative complications, body weight (BW), food intake and necropsy data were recorded. RESULTS: Five minipigs survived without complications to the end of the study. Four minipigs developed surgical related complications and were euthanized while two minipigs died due to central venous catheter related complications. BW and food intake is reported for the six minipigs surviving longer than 4.5 months post-surgery. Weight loss and reduced food intake was seen in all minipigs. After 2-3 months of weight loss, weight regain was evident in all but two minipigs which seemed to continue losing weight. Necropsy revealed some variation in the length of the alimentary, biliary and common limb between minipigs. CONCLUSION: The use of obese Göttingen minipigs as a translational RYGBP model is feasible and has potential for the study of RYGBP-related changes in gut function, type-2 diabetes and appetite regulation. Still, the surgical procedure is technically highly demanding in obese Göttingen minipigs and the peri-operative animal care and follow up requires close monitoring.