PKN1 Kinase: A Key Player in Adipocyte Differentiation and Glucose Metabolism.

Adipocyte dysfunction is the driver of obesity and correlates with insulin resistance and the onset of type 2 diabetes. Protein kinase N1 (PKN1) is a serine/threonine kinase that has been shown to contribute to Glut4 translocation to the membrane and glucose transport. Here, we evaluated the role of PKN1 in glucose metabolism under insulin-resistant conditions in primary visceral adipose tissue (VAT) from 31 patients with obesity and in murine 3T3-L1 adipocytes. In addition, in vitro studies in human VAT samples and mouse adipocytes were conducted to investigate the role of PKN1 in the adipogenic maturation process and glucose homeostasis control. We show that insulin-resistant adipocytes present a decrease in PKN1 activation levels compared to nondiabetic control counterparts. We further show that PKN1 controls the adipogenesis process and glucose metabolism. PKN1-silenced adipocytes present a decrease in both differentiation process and glucose uptake, with a concomitant decrease in the expression levels of adipogenic markers, such as PPARγ, FABP4, adiponectin and CEBPα. Altogether, these results point to PKN1 as a regulator of key signaling pathways involved in adipocyte differentiation and as an emerging player of adipocyte insulin responsiveness. These findings may provide new therapeutic approaches for the management of insulin resistance in type 2 diabetes.

Irisin as a Novel Biomarker of Subclinical Atherosclerosis in Severe Obesity.

Severe obesity (SO) can accelerate atherosclerosis and the onset of acute cardiovascular events. The diagnosis of atherosclerosis in the context of a high body mass index (BMI) can be challenging, making the identification of biomarkers clinically relevant. We aimed to assess the usefulness of irisin as a biomarker for subclinical atherosclerosis in participants with SO. This prospective observational study included 61 participants undergoing bariatric surgery for SO, defined as a BMI >40 kg/m2 or >35 kg/m2 with at least one comorbidity. Atherosclerotic plaques were detected by ultrasound. Plasma samples were obtained 1 month before and at 6 and 12 months after bariatric surgery to measure irisin by ELISA. Additionally, subcutaneous samples of adipose tissue were taken and genotyped to identify irisin polymorphism rs3480. Irisin levels were positively correlated with BMI (r = 0.23, p = 0.0064), negatively correlated with atheroma-related parameters (e.g., carotid intima-media thickness), and lower in subjects with atheroma (p < 0.0002). Irisin also showed good overall accuracy for discriminating plaque presence (AUC, 0.81; 95% CI, 0.6956-0.9156). However, the rs3480 polymorphism correlated with neither the irisin levels nor the presence of atheromas. Iirisin could identify subclinical atherosclerosis in SO and might facilitate clinical diagnosis.

Effect of bariatric surgery on inflammation and endothelial dysfunction as processes underlying subclinical atherosclerosis in morbid obesity.

BACKGROUND: Inflammation and endothelial dysfunction are associated with morbid obesity (MO) and atherosclerosis. OBJECTIVE: To evaluate inflammation and endothelial function as the initial mechanisms underlying subclinical atherosclerosis in patients with MO, with and without atheromas, and their evolution after bariatric surgery (BS). SETTING: Arnau de Vilanova University Hospital and University of Barcelona. METHODS: Plasma samples from 66 patients with MO were obtained before BS and 6 and 12 months after BS. Patients were divided into 2 groups based on the presence of atheromatous plaques (detected by ultrasound imaging). RESULTS: Inflammation was increased as demonstrated by changes in the levels of fibroblast growth factor 21, adiponectin, leptin, interleukin 6, tumor growth factor α, nonesterified free fatty acids, lipoprotein(a) and C-reactive protein (CRP). Endothelial dysfunction was characterized by impaired angiogenesis (measured through angiopoietin 1 and 2 and brain-derived neurotrophic factor), vascular function (changes in endothelin 1 and thrombomodulin levels), and diapedesis (changes in intercellular and vascular cell adhesion molecules, and E- and P-selectins). Both mechanisms occurred regardless of the presence of atheromas. BS ameliorated both processes even in patients who already had subclinical atherosclerosis. However, CRP, thrombomodulin, and P-selectin levels were higher in patients with atheromas. CONCLUSIONS: Endothelial dysfunction and inflammation were detected before the appearance of structural changes in vessel walls on ultrasonography images. BS might prevent or slow atherogenesis in the early stages by breaking the vicious circle between inflammation and endothelial dysfunction. CRP, thrombomodulin, and P-selectin may have a critical role in plaque development and, together with the study of endothelial dysfunction, might be useful in assessing early atherosclerosis and its evolution after BS.

Impact of bariatric surgery on subclinical atherosclerosis in patients with morbid obesity.

BACKGROUND: The main cause of death in obese individuals is cardiovascular disease precipitated by atherosclerosis. Endothelial dysfunction and inflammation are considered early events in the development of the disease. OBJECTIVES: The aim of this study was to identify biomarkers of subclinical atherosclerosis in patients with morbid obesity by comparing clinical, vascular, and biochemical parameters indicative of endothelial dysfunction in patients with and without atheromatous plaque and monitoring changes after bariatric surgery. SETTINGS: Multicenter collaboration between Biochemistry and Biomedicine Department in Barcelona University and University Hospital Arnau de Vilanova in Lleida. METHODS: Plasma samples from 66 patients with morbid obesity were obtained before bariatric surgery and at 6 and 12 months after. Patients were divided into 2 groups based on the presence of atheromatous plaque. We used contrast-enhanced carotid ultrasound, enzyme-linked immunosorbent assay, Griess, and EndoPAT-2000 methods. RESULTS: Patients with plaque showed the worst profile of cardiovascular risk factors. Carotid intima-media thickness and plasminogen activator inhibitor-1 were higher in plaque group (P < .0001). After bariatric surgery, vasa vasorum, oxidized low-density lipoprotein, and plasminogen activator inhibitor-1 decreased (P < .0001 in all cases). CONCLUSIONS: Obesity promotes atherogenesis, leading to vascular endothelial damage. Bariatric surgery reduces cardiovascular risk and the prognosis is better for patients without plaque. The increase in plasminogen activator inhibitor-1, carotid intima-media thickness, and vasa vasorum proliferation might be the first alterations in the atheromatous process in obesity and could serve as good biomarkers of subclinical atherosclerosis.

Bariatric surgery decreases oxidative stress and protein glycosylation in patients with morbid obesity.

BACKGROUND: There is growing evidence that oxidative stress (OS) is a critical factor linking obesity with its associated comorbidities, such as cardiovascular diseases. AIM: To evaluate the degree of OS in people with morbid obesity and its relationship with glycoproteins, determined using 1H-NMR spectroscopy, before and after bariatric surgery (BS). METHODS: In this observational cohort study, plasma from 24 patients with BMI ≥ 40 kg/m2 (age: 21-65 years) was used to measure metabolites implicated in OS. We measured glycoprotein (GlycA, GlycB and GlycF) areas and shape factors (H/W = height/width). RESULTS: One year after BS, oxidized low-density lipoprotein had decreased by 49% (P < .0001), malondialdehyde by 32% (P = .0019) and lipoprotein (a) by 21% (P = .0039). The antioxidant enzymes paraoxonase-1 and catalase increased after BS (43%, P < .0001 and 54%, P = .0002, respectively). Superoxide dismutase-2 had fallen 1 year after BS (32%, P = .0052). After BS, both the glycoprotein areas and shape factors decreased by 20%-26%. These glycoproteins were significantly correlated with OS parameters. The plasma atherogenic index was 63% higher in obese individuals than 1 year after BS and correlated positively with glycoproteins. CONCLUSION: For the first time, we here demonstrate the relationship between OS parameters and glycoproteins in people with morbid obesity. So glycoproteins could therefore be a good indicator, together with the oxidative state to assess patient prognosis after BS.

Effect of bariatric surgery in the evolution of oxidative stress depending on the presence of atheroma in patients with morbid obesity.

BACKGROUND: Morbid obesity is associated with accelerated atherosclerosis, a chronic vascular disease related to oxidative stress (OS) and endothelial dysfunction. OBJECTIVES: We aimed to evaluate the effect of bariatric surgery (BS) on oxidative stress as a cardiovascular risk factor in patients with and without atheromatous plaques. SETTING: Arnau de Vilanova University Hospital and University of Barcelona. METHODS: Plasma samples from 66 patients with morbid obesity were obtained before BS and 6 and 12 months after. Patients were divided into 2 groups based on the presence of atheromatous plaques (detected by ultrasonography). OS parameters were measured by enzyme-linked immunosorbent assay. RESULTS: Patients with morbid obesity had OS independently of the presence of an atheroma, but oxidized low-density lipoprotein levels were higher in patients with plaques throughout the study (P = .0430). After surgery, oxidized low-density lipoprotein and malondialdehyde levels decreased significantly (P < .0001 in both cases). At the beginning of the study, antioxidant enzyme levels were the same between the groups. After surgery, paraoxonase 1 levels were increased (P < .0001) in the group without plaque, being significantly higher (P = .0147). Superoxide dismutase 2 levels were only decreased in patients without plaque (P < .0010), while catalase activity was higher in patients with plaque. CONCLUSIONS: Morbid obesity may lead to chronic OS, which increases predisposition to atherogenesis. BS improves the antioxidant profile and reduces OS and co-morbidities in both groups. However, the benefits are greater for patients without plaque. Therefore, BS may prevent atheroma formation and also could prevent plaque rupture by decreasing OS.

Diet change affects intestinal microbiota restoration and improves vertical sleeve gastrectomy outcome in diet-induced obese rats.

PURPOSE: Obesity, a worldwide health problem, is linked to an abnormal gut microbiota and is currently most effectively treated by bariatric surgery. Our aim was to characterize the microbiota of high-fat fed Sprague-Dawley rats when subjected to bariatric surgery (i.e., vertical sleeve gastrectomy) and posterior refeeding with either a high-fat or control diet. We hypothesized that bariatric surgery followed by the control diet was more effective in reverting the microbiota modifications caused by the high-fat diet when compared to either of the two factors alone. METHODS: Using next-generation sequencing of ribosomal RNA amplicons, we analyzed and compared the composition of the cecal microbiota after vertical sleeve gastrectomy with control groups representing non-operated rats, control fed, high-fat fed, and post-operative diet-switched animals. Rats were fed either a high-fat or control low-fat diet and were separated into three comparison groups after eight weeks comprising no surgery, sham surgery, and vertical sleeve gastrectomy. Half of the rats were then moved from the HFD to the control diet. Using next-generation sequencing of ribosomal RNA amplicons, we analyzed the composition of the cecal microbiota of rats allocated to the vertical sleeve gastrectomy group and compared it to that of the non-surgical, control fed, high-fat fed, and post-operative diet-switched groups. Additionally, we correlated different biological parameters with the genera exhibiting the highest variation in abundance between the groups. RESULTS: The high-fat diet was the strongest driver of altered taxonomic composition, relative microbial abundance, and diversity in the cecum. These effects were partially reversed in the diet-switched cohort, especially when combined with sleeve gastrectomy, resulting in increased diversity and shifting relative abundances. Several highly-affected genera were correlated with obesity-related parameters. CONCLUSIONS: The dysbiotic state caused by high-fat diet was improved by the change to the lower fat, higher fiber control diet. Bariatric surgery contributed significantly and additively to the diet in restoring microbiome diversity and complexity. These results highlight the importance of dietary intervention following bariatric surgery for improved restoration of cecal diversity, as neither surgery nor change of diet alone had the same effects as when combined.

Adipose Tissue Protein Glycoxidation is Associated with Weight-Loss Potential.

OBJECTIVE: This study aimed to characterize the differences in protein oxidation biomarkers in adipose tissue (AT) as an indicator of AT metabolism and bariatric surgery weight-loss success. METHODS: A human model, in which sixty-five individuals with obesity underwent bariatric surgery, and a diet-induced obesity animal model, in which animals were treated for 2 months with normocaloric diets, were analyzed to determine the associations between AT protein oxidation and body weight loss. Protein oxidative biomarkers were determined by gas chromatography/mass spectrometry in AT from human volunteers before the surgery, as well as 2 months after a diet treatment in the animal model. RESULTS: The levels of carboxyethyl-lysine (CEL) and 2-succinocystein (2SC) in both visceral and subcutaneous AT before the surgery directly correlated with greater weight loss in both human and animal models. 2SC levels in subcutaneous AT greater than 4.7 × 106  µmol/mol lysine (95% CI: 3.4 × 106 to 6.0 × 106 ) may predict greater weight loss after bariatric surgery (receiver operating characteristic curve area = 0.8222; P = 0.0047). Additionally, it was observed that individuals with diabetes presented lower levels of CEL and 2SC in subcutaneous AT (P = 0.0266 and P = 0.0316, respectively) compared with individuals without diabetes. CONCLUSIONS: CEL and 2SC in AT are useful biomarkers of AT metabolism and predict the individual's ability to reduce body weight after bariatric surgery.

Magnetic detection of sentinel lymph node in papillary thyroid carcinoma: The MAGIC-PAT study results.

INTRODUCTION: Despite the controversy concerning sentinel lymph node biopsy (SLNB) in papillary thyroid carcinoma (PTC), successful detection rates can be achieved by radioguidance and vital dyeing. However, the drawbacks in both techniques are notable. Magnetic-guided SLNB (mSLNB) using superparamagnetic iron oxide (SPIO) nanoparticles is appealing as an alternative procedure. MATERIALS AND METHODS: mSLNB using the Sentimag-Sienna System®, total thyroidectomy and central compartment dissection (CCD) were performed on all PTC patients. Lymph node involvement was assessed by postoperative pathological examination. RESULTS: From 2014 to 2016, 33 consecutive patients with PTC were enrolled in the study. A total of 20 patients met the eligibility. mSLNB succeeded in 16 patients, with a detection rate of 80%. A median of two SLN per patient were detected. A median of 10.5 non-sentinel lymph nodes (NSLN) from CCD were examined. Among the patients, 56.25% (9/16) had no metastatic nodes, while 12.5% (2/16) had exclusively SLN involvement. No false negative cases were found. The agreement between SLN and NSLN status was 87.5%. The prediction of NSLN involvement by SLN status showed 100% sensitivity, 81.8% specificity, 71.4% PPV and 100% NPV. Subsequently, mSLNB and the final pathological analysis would discriminate 43.75% (7/16) of patients who would certainly benefit from CCD whilst 56.25% of the total would confirm an unnecessary lymphadenectomy and avoid morbidity. CONCLUSION: mSLNB showed satisfactory performance in PTC with clinical-negative nodes. We have shown mSLNB to be a good predictor of central compartment status that can improve the staging and management of PTC patients.

Influence of Morbid Obesity and Bariatric Surgery Impact on the Carotid Adventitial Vasa Vasorum Signal.

INTRODUCTION/PURPOSE: Adventitial vasa vasorum (VV) expansion to the avascular intima precedes an increase in carotid intima-media thickness. However, factors involved in the development of the atherosclerotic process and its reversibility remain unclear. We aimed to evaluate the VV signal in both morbid obesity and after bariatric surgery (BS). MATERIALS/METHODS: We conducted a case-control study to examine the VV signal in the carotid of 40 morbidly obese patients and 40 non-obese controls. The effect of BS was evaluated in 33 patients. Contrast-enhanced carotid ultrasound was used to assess the VV signal. RESULTS: The mean VV density was higher in obese than in non-obese subjects (0.739 ± 0.117 vs. 0.570 ± 0.111, p < 0.001). The VV signal positively correlated with BMI (p < 0.001) and waist circumference (p = 0.001) but was not related to cIMT. The stepwise multivariate regression analysis revealed that waist circumference (beta = 0.507, p < 0.001) together with fasting plasma glucose (beta = 0.229, p = 0.024) were independently associated with the VV signal (R2 = 0.382). Before BS, the median VV signal correlated with soluble intercellular adhesion molecule 1 (p = 0.022). After a 12-month follow-up, a 12.0% decrease in VV (0.731 ± 0.126 vs. 0.643 ± 0.115, p = 0.003) was observed. In the univariate analysis, the decrease in VV was associated with the baseline VV density (p < 0.001), baseline systolic blood pressure (p = 0.019) and a decrease in sICAM (p = 0.005). However, only baseline systolic pressure (beta = 0.417, p = 0.024) independently predicted the absolute change in VV signal (R2 = 0.174). CONCLUSIONS: Morbidly obesity is associated with increased VV density. In addition, BS appears to reduce the earlier expansion of the adventitial vasa vasorum.

Advanced glycation end-products in morbid obesity and after bariatric surgery: When glycemic memory starts to fail. / Productos finales de glicación avanzada en la obesidad mórbida y tras la cirugía bariátrica: cuando la memoria glucémica empieza a fallar.

BACKGROUND AND OBJECTIVE: Advanced glycation end-products (AGEs) are a marker of metabolic memory. Their levels increases when oxidative stress, inflammation, or chronic hyperglycemia exists. The role of morbid obesity in AGE levels, and the impact of bariatric surgery on them are unknown. PATIENTS AND METHOD: An observational study with three sex- and age-matched cohorts: 52 patients with obesity, 46 patients undergoing bariatric surgery in the last 5 years, and 46 control subjects. AGE were measured using skin autofluorescence (SAF) in the forearm with an AGE Reader™ (DiagnOptics Technologies, Groningen, The Netherlands). Presence of metabolic syndrome was assessed. RESULTS: Patients with morbid obesity had higher SAF levels (2.14±0.65AU) than non-obese subjects (1.81±0.22AU; P<.001), which was mainly attributed to obese subjects with metabolic syndrome (2.44±0.67 vs. 1.86±0.51AU; P<.001). After bariatric surgery, SAF continued to be high (2.18±0.40AU), and greater as compared to the non-obese population (P<.001). A multivariate analysis showed that age and presence of metabolic syndrome (but not sex or body mass index) were independently associated to SAF (R2=0.320). CONCLUSION: SAF is increased in patients with morbid obesity and metabolic syndrome, mainly because of the existence of type 2 diabetes mellitus. In the first 5 years following bariatric surgery, weight loss and metabolic improvement are not associated with a parallel decrease in subcutaneous AGE levels.

Diet Change After Sleeve Gastrectomy Is More Effective for Weight Loss Than Surgery Only.

BACKGROUND: Bariatric surgery with or without diet change has become one of the most effective treatments for obesity. The objective of this study was to observe the effects of vertical sleeve gastrectomy (VSG) and diet change in Sprague-Dawley rats on both body and tissue weights. METHODS: Eighteen rats were fed with a standard chow diet (SCD) (C group), and 36 rats were fed with a high-fat diet (HFD) (diet-induced obesity (DIO) group). After 8 weeks, the animals underwent VSG, sham surgery or no surgery (NS). After surgery, a third of the rats fed with the HFD changed to the SCD (DIO + C group). Body weight, food and energy intake were recorded daily during the experiment (12 weeks). Food efficiency (%) (FE) was determined from weekly weight gain and weekly kilocalorie consumed measurements. RESULTS: The DIO group had higher and significant weight gain than the C group at the time of surgery (p < 0.001). The major weight loss (WL) was observed in the DIO + C-VSG group, during the 4 weeks after surgery. Adipose tissues in the DIO + C-VSG group were drastically reduced and had a weight similar to those in the C-VSG group. CONCLUSION: VSG and the diet change combination led to a greater WL, which was maintained during the 4 weeks post-surgery, leading to a normalization of body weight. VSG and diet change also affected most of the tissues, not only adipose, showing a global change in whole body composition.

Productos finales de glicación avanzada en la obesidad mórbida y tras la cirugía bariátrica: cuando la memoria glucémica empieza a fallar / Advanced glycation end-products in morbid obesity and after bariatric surgery: When glycemic memory starts to fail

Antecedentes y objetivo: Los productos finales de glicación avanzada (AGE) son un indicador de memoria metabólica. Su concentración se incrementa cuando existe estrés oxidativo, inflamación o hiperglucemia crónica. Se desconoce el papel de la obesidad mórbida en su concentración, así como la influencia que la cirugía bariátrica ejerce sobre ellos. Pacientes y método: Estudio observacional con 3 cohortes equiparadas por sexo y edad: 52 pacientes con obesidad, 46 sometidos a cirugía bariátrica en los últimos 5 años y 46 sujetos control. La determinación de los AGE se realizó mediante autofluorescencia cutánea (SAF) del antebrazo con un AGE Reader(TM) (DiagnOptics Technologies, Groningen, Países Bajos). Se evaluó la presencia de síndrome metabólico. Resultados: Los sujetos con obesidad mórbida presentaron una SAF (2,14±0,65AU) superior a la de la población no obesa (1,81±0,22AU; p<0,001). Este incremento fue a expensas de aquellos sujetos obesos con síndrome metabólico (2,44±0,67 vs. 1,86±0,51AU; p<0,001). Tras la cirugía bariátrica, la SAF se mantuvo elevada (2,18±0,40AU) y superior a la de la población no obesa (p<0,001). El análisis multivariante mostró que la edad y la presencia de síndrome metabólico (pero no el sexo, ni el índice de masa corporal) se asociaron independientemente con la SAF (R2=0,320). Conclusiones: En la obesidad mórbida acompañada de síndrome metabólico existe un incremento de la SAF, a expensas principalmente de la presencia de diabetes tipo 2. En los primeros 5 años tras la cirugía, la pérdida ponderal y la mejoría metabólica no se acompañan de un descenso paralelo de la concentración tisular de AGE (AU)

Background and objective: Advanced glycation end-products (AGEs) are a marker of metabolic memory. Their levels increases when oxidative stress, inflammation, or chronic hyperglycemia exists. The role of morbid obesity in AGE levels, and the impact of bariatric surgery on them are unknown. Patients and method: An observational study with three sex- and age-matched cohorts: 52 patients with obesity, 46 patients undergoing bariatric surgery in the last 5 years, and 46 control subjects. AGE were measured using skin autofluorescence (SAF) in the forearm with an AGE Reader(TM) (DiagnOptics Technologies, Groningen, The Netherlands). Presence of metabolic syndrome was assessed. Results: Patients with morbid obesity had higher SAF levels (2.14±0.65AU) than non-obese subjects (1.81±0.22AU; P<.001), which was mainly attributed to obese subjects with metabolic syndrome (2.44±0.67 vs. 1.86±0.51AU; P<.001). After bariatric surgery, SAF continued to be high (2.18±0.40AU), and greater as compared to the non-obese population (P<.001). A multivariate analysis showed that age and presence of metabolic syndrome (but not sex or body mass index) were independently associated to SAF (R2=0.320). Conclusion: SAF is increased in patients with morbid obesity and metabolic syndrome, mainly because of the existence of type 2 diabetes mellitus. In the first 5 years following bariatric surgery, weight loss and metabolic improvement are not associated with a parallel decrease in subcutaneous AGE levels (AU)

Diabetic and dyslipidaemic morbidly obese exhibit more liver alterations compared with healthy morbidly obese.

BACKGROUND & AIMS: To study the origin of fat excess in the livers of morbidly obese (MO) individuals, we analysed lipids and lipases in both plasma and liver and genes involved in lipid transport, or related with, in that organ. METHODS: Thirty-two MO patients were grouped according to the absence (healthy: DM - DL -) or presence of comorbidities (dyslipidemic: DM - DL +; or dyslipidemic with type 2 diabetes: DM + DL +) before and one year after gastric bypass. RESULTS: The livers of healthy, DL and DM patients contained more lipids (9.8, 9.5 and 13.7 times, respectively) than those of control subjects. The genes implicated in liver lipid uptake, including HL, LPL, VLDLr, and FAT/CD36, showed increased expression compared with the controls. The expression of genes involved in lipid-related processes outside of the liver, such as apoB, PPARα and PGC1α, CYP7a1 and HMGCR, was reduced in these patients compared with the controls. PAI1 and TNFα gene expression in the diabetic livers was increased compared with the other obese groups and control group. Increased steatosis and fibrosis were also noted in the MO individuals. CONCLUSIONS: Hepatic lipid parameters in MO patients change based on their comorbidities. The gene expression and lipid levels after bariatric surgery were less prominent in the diabetic patients. Lipid receptor overexpression could enable the liver to capture circulating lipids, thus favouring the steatosis typically observed in diabetic and dyslipidaemic MO individuals.

Hepatic and visceral adipose tissue 11ßHSD1 expressions are markers of body weight loss after bariatric surgery.

OBJECTIVE: Cortisolemia and 11ßHSD1 in liver and adipose tissue are altered in obesity. However, their participation in the development of obesity remains unclear. This study analyzed these parameters in the transition from morbid to type 1 obesity after bariatric surgery. METHODS: A group of 34 patients with morbid obesity and 22 nonobese subjects were recruited. Initial hypothalamus-pituitary-adrenal (HPA) basal activity and 11ßHSD1 mRNA expression in liver, subcutaneous (SAT), and visceral adipose tissue (VAT) were evaluated. A year after bariatric surgery (weight loss of 48 kg), these parameters were reappraised in plasma, SAT, and liver. RESULTS: Body weight loss was accompanied by a downshift in basal HPA activity and 11ßHSD1 expression in SAT. In patients with morbid obesity, 11ßHSD1 expression correlated positively with BMI in VAT and negatively in liver at 6 and 12 months after surgery. In SAT, a correlation was observed with body weight only when patients showed type 1 obesity. Insulin, glucose, and HOMA correlated positively with all the HPA indicators and 11ßHSD1 expression in SAT. CONCLUSIONS: Body weight loss after bariatric surgery is accompanied by a downshift in basal HPA activity. Hepatic and VAT 11ßHSD1 expressions in morbid obesity are predictors of body weight loss.

Haematological parameters and serum trace elements in "healthy" and "unhealthy" morbidly obese patients before and after gastric bypass.

BACKGROUND & AIMS: We have investigated the differences in plasma parameters and serum trace elements between "healthy" and unhealthy morbidly obese patients before and after Roux-en-Y gastric bypass surgery. METHODS: A group of 32 morbidly obese patients undergoing bariatric surgery were divided into three groups. Group 1 subjects were free of dyslipidemia and type II diabetes mellitus (defined as "healthy" obese, DM-DL-); Group 2 subjects had only the presence of dyslipidemia (DM-DL+), while group 3 patients demonstrated the presence of both (DM + DL+). In all patients, we studied haematological, haemostasis, anaemia, coagulation plasma and trace elements parameters before and 1, 6 and 12 months after gastric bypass surgery. RESULTS: We found significant differences in some haematological parameters, including haemostasis (e.g., T-Quick, p = 0.0048) and coagulation (e.g., ATIII and PAI-1, p = 0.001 and p < 0.0001, respectively) and in anaemia parameters (e.g., folate, cobalamin and transferrin, p = 0.0002, p < 0.0001 and p = 0.0001, respectively) but also in serum trace elements between the groups. However, the response to bariatric surgery was similar in the three groups. CONCLUSION: Any healthy morbid obese subject is really metabolically "unhealthy" because he or she has many other haematologic or serum abnormalities that are often not included in the criteria for the definition of "healthy" in these obese subjects.

Morbidly "Healthy" Obese Are Not Metabolically Healthy but Less Metabolically Imbalanced Than Those with Type 2 Diabetes or Dyslipidemia.

BACKGROUND: We have investigated the differences between metabolically "healthy" morbidly obese patients and those with comorbidities. MATERIALS AND METHODS: Thirty-two morbidly obese patients were divided by the absence ("healthy": DM-DL-) or presence of comorbidities (dyslipidemic: DM-DL+, or dyslipidemic and with type 2 diabetes: DM+DL+). We have studied various plasma parameters and gene expression adipose tissue, before and after gastric bypass. RESULTS: The group DM+DL+ tends to have lower values than the other two groups for anthropometric parameters. Regarding the satiety parameters, only leptin (p = 0.0024) showed a significant increase with comorbidities. Lipid parameters showed significant differences among groups, except for phospholipids and NEFA. For insulin resistance parameters, only glucose (p < 0.0001) was higher in DM+DL+ patients, but not insulin or homeostasis model assessment of insulin resistance (HOMA-IR). The gene expression of adiponectin, insulin receptor (INSR) and glucose receptor-4 (GLUT4), in the subcutaneous fat, decreased in all groups vs. a non-obese control. Interleukin-6 (IL6) and the inhibitor of plasminogen activator type 1 (PAI-1) genes decreased only in DM-DL+ and DM+DL+, but not in "healthy" patients. Leptin increased in all groups vs. the non-obese control. The visceral fat from DM+DL+ patients showed a sharp decrease in adiponectin, GLUT4, IL6 and PAI-1. All parameters mentioned above improved very significantly by surgery, independent of the occurrence of comorbidities. CONCLUSIONS: The morbidly obese "healthy" individual is not really metabolically healthy, but morbidly obese individuals with diabetes and dyslipidemia are more metabolically imbalanced.

Decreased lipases and fatty acid and glycerol transporter could explain reduced fat in diabetic morbidly obese.

OBJECTIVE: The possible differences were investigated in 32 morbidly obese patients depending on whether they were "healthy" or had dyslipidemia and/or type 2 diabetes. METHODS: Lipid metabolism and insulin resistance were analyzed in subcutaneous (SAT) and visceral adipose tissue (VAT) before and during 6 and 12 months after Roux-en-Y gastric bypass. RESULTS: Significant differences have been found in lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activities in SAT from the different obese group versus normal weight (control) but not between them. The reduced lipase activities in VAT were 43 and 19% smaller (22 and 4% smaller, respectively, vs. control) than the "healthy" obese group for LPL and HSL, respectively, and were accompanied with a reduced expression of these lipases, as well as decreased expression of FAT/CD36, FABP4, and AQ7 in that tissue. In addition, the expression of the other genes measured showed a downregulation not only versus the "healthy" obese but also versus the normal weight group. CONCLUSIONS: Being obese is not "healthy," but it is even less so if morbidly obese patients with diabetes and dyslipidemia were considered. The reduced fat accumulation in these patients may be attributed to the decrease of the expression and activity of the lipases of their adipose tissue.

Abordaje del bocio endotorácico en mediastino posterior: incisión transcervical y toracotomía lateral / Best Approach for Posterior Mediastinal Goiter Removal: Transcervical Incision and Lateral Thoracotomy

La extirpación quirúrgica del bocio intratorácico puede realizarse a través de un abordaje cervical en la mayoría de los pacientes. La revisión de la literatura pone de manifiesto que los cirujanos experimentados precisan un abordaje extracervical en el 2-3% de los casos. A pesar de que el tratamiento quirúrgico del bocio retroesternal está bien definido, existe poca información acerca del abordaje quirúrgico de los bocios intratorácicos que se extienden más allá del cayado aórtico hacia el mediastino posterior. Presentamos 2 casos y proponemos una combinación de incisión cervical y toracotomía lateral con preservación muscular para la resección del bocio en el mediastino posterior. En este tipo de casos descartamos el uso de la esternotomía puesto que el mediastino posterior resulta inaccesible debido a la presencia del corazón y grandes vasos por delante de la masa tiroidea, lo cual podría llevar a realizar una peligrosa disección a ciegas. Según nuestra experiencia el abordaje transcervical combinado con la toracotomía está indicado para una resección completa y segura del bocio situado en el mediastino posterior

Surgical removal of intrathoracic goiter can be performed by a cervical approach in the majority of patients. Review of literature shows that experienced surgeons need to perform an extracervical approach in 2-3% of cases. In spite of surgical management of substernal goiter is well defined, there is little available information about surgical approach of intrathoracic goiters extending beyond the aortic arch into the posterior mediastinum. We report two cases and propose combination of cervical incision and muscle-sparing lateral thoracotomy for posterior mediastinal goiter removal. In such cases, we do not favor sternotomy as posterior mediastinum is inaccessible due to the presence of heart and great vessels anterior to the thyroidal mass that would lead to perform a perilous blind dissection. Based on our experience, transcervical and thoracotomy approach is indicated for a complete and safe posterior mediastinal goiter remova