Alberto Diez-Caballero

The Decrease in Plasma Ghrelin Concentrations following Bariatric Surgery Depends on the Functional Integrity of the Fundus

Background: Gastric bypass surgery, which involves the production of a reduced stomach pouch,has been shown to markedly suppress circulating ghrelin concentrations. Since bypassing the ghrelin-producing cell population may be relevant to the disruption of fundic-derived factors participating in food intake signaling, the effect of weight loss induced by either adjustable gastric banding (AGB), Roux-en-Y gastric bypass (RYGBP) or biliopancreatic diversion (BPD) was studied. Methods: 16 matched obese patients [35.0 + 2.4 years; initial body weight 124.8 ± 5.7 kg; body mass index (BMI) 47.1 ± 2.2 kg/m2] in whom similar weight loss had been achieved by either AGB (n=7), RYGBP (n=6) or BPD (n=3) were studied. Blood was obtained for biochemical and hormonal analyses. Body composition was assessed by air-displacement-plethysmography. Results: Comparable weight loss (AGB: 26.1 ± 5.1 kg; RYGBP: 32.1 ± 5.0; BPD: 31.7 ± 6.1; P=NS) and decrease in percentage body fat (AGB: 10.0 ± 1.5%; RYGBP: 14.2 ± 2.8; BPD: 10.3 ± 1.0; P=NS) induced by bariatric surgery exerted significantly different (P=0.004) effects on plasma ghrelin concentrations, depending on the surgical procedure applied (AGB: 480 ± 78 pg/ml; RYGBP: 117 ± 34; BPD: 406 ± 86). Without significant differences in BMI, body fat, glucose, triglycerides, cholesterol, insulin and leptin levels, patients who had undergone the RYGBP exhibited statistically significant diminished circulating fasting plasma ghrelin concentrations compared with the other two bariatric techniques which conserve direct contact of the fundus with ingested food (P=0.003 vs AGB and P=0.020 vs BPD). Conclusion: Fasting circulating ghrelin concentrations in patients undergoing diverse bariatric operations depend on the degree of dysfunctionality of the fundus.

Gene expression profile of omental adipose tissue in human obesity

The aim of the present study was to gain insight into the pathophysiology of obesity by comparing the pattern of gene expression of omental adipose tissue of obese and lean volunteers using DNA microarrays. Omental adipose tissue biopsies were obtained by laparoscopic surgery from six male patients (44.2±6.3 yr). RNA was extracted and pooled for the obese (BMI: 37.3±2.5 kg/m2) and lean (BMI: 23.4±0.8 kg/m2) groups. From the total number of genes analyzed (1,152 well‐characterized human genes), 41% were expressed at sufficient levels in human adipose tissue for detection in the microarray experiments, finding that 89 genes were up‐ regulated while 64 were down‐regulated at least twofold in the omental adipose tissue obtained from obese patients. We found a general tendency to blunt lipolysis inducer genes and a global down‐regulation of genes encoding growth factors. Moreover, an up‐regulation in the expression of several mitogen‐activated protein kinases (MAPKs) was observed. The down‐regulation of genes involved in lipolysis activation may be involved in the etiopathogenesis of obesity. In addition, down‐regulation of growth factors and the up‐regulation of MAPKs may indicate an attempt to restrain adipocyte proliferation and differentiation. Furthermore, obesity is accompanied by an altered expression in omental adipose tissue of genes involved not only in energy homeostasis but also in quite diverse biological functions, such as immune response. The genomic approach underlines the importance of adipose tissue beyond energy metabolism.

The subcutaneous adipose tissue reservoir of functionally active stem cells is reduced in obese patients

It has been demonstrated that the adipose tissue, a highly functional metabolic tissue, is a reservoir of mesenchymal stem cells. The potential use of adipose‐derived stem cells (ADSCs) from white adipose tissue (WAT) for organ repair and regeneration has been considered because of their obvious benefits in terms of accessibility and quantity of available sample. However, the functional capability of ADSCs from subjects with different adiposity has not been investigated. It has been our hypothesis that ADSCs from adipose tissue of patients with metabolic syndrome and high adiposity may be functionally impaired. We report that subcutaneous WAT stromal vascular fraction (SVF) from nonobese individuals had a significantly higher number of CD90+ cells than SVF from obese patients. The isolated ADSCs from WAT of obese patients had reduced differentiation potential and were less proangiogenic. Therefore, ADSCs in adipose tissue of obese patients have lower capacity for spontaneous or therapeutic repair than ADSCs from nonobese metabolically normal individuals.—Oñate, B., Vilahur, G., Ferrer‐Lorente, R., Ybarra, J., Díez‐Caballero, A., Ballesta‐López, C., Moscatiello, F., Herrero, J., Badimon, L. The subcutaneous adipose tissue reservoir of functionally active stem cells is reduced in obese patients. FASEB J. 26, 4327–4336 (2012). www.fasebj.org

Involvement of leptin in the association between percentage of body fat and cardiovascular risk factors.

OBJECTIVESnRecent epidemiologic studies have shown that obesity is associated with elevated blood concentrations of prothrombotic-proinflammatory factors and markers of endothelial dysfunction such as fibrinogen, C-reactive protein (CRP), von Willebrand factor (vWF), and homocysteine. We have assessed whether these markers are associated with percentage of body fat (BF), insulin sensitivity as well as with leptin concentrations.nnnDESIGN AND METHODSnTwenty-five men aged 49.6 +/- 12.7 yr (mean +/- SD) underwent whole-body air displacement plethysmography (Bod-Pod(R)) for estimating BF. Blood analyses for leptin and several other metabolic and cardiovascular markers were carried out.nnnRESULTSnObese subjects had higher levels as compared to controls of BF (37.5 +/- 5.1 vs. 26.0 +/- 6.6, p < 0.01), fibrinogen (3.30 +/- 0.43 vs. 2.67 +/- 0.11, p < 0.01), vWF (136.4 +/- 50.4% vs. 81.6 +/- 12.6%, p < 0.05), and leptin (17.6 +/- 8.7 vs. 6.2 +/- 3.3, p < 0.01), lower concentrations of HDL-cholesterol (1.09 +/- 0.20 vs. 1.51 +/- 0.10, p < 0.001) and lower QUICKI (1/[log(Ins(0)) + log(Glu(0))]) (0.31 +/- 0.03 vs. 0.34 +/- 0.02, p < 0.05). No significant changes were observed in CRP (5.7 +/- 3.4 vs. 3.8 +/- 1.6, p = 0.327) and homocysteine (9.4 +/- 4.2 vs. 8.3 +/- 0.9, p = 0.749). A positive correlation was observed between BF and fibrinogen (r = 0.67, p = 0.0003). Plasma leptin concentrations were correlated with fibrinogen (r = 0.71, p = 0.0001) and CRP (r = 0.43, p = 0.044). After adjustment for BF leptin emerged as a significant predictor of fibrinogen (beta = 0.47, p = 0.023; R(2) = 0.59, p < 0.001). QUICKI was positively correlated with HDL-cholesterol (r = 0.59, p = 0.010) and negatively with fibrinogen (r = -0.53, p = 0.025), CRP (r = -0.52, p = 0.028) and vWF (r = -0.56, p = 0.013).nnnCONCLUSIONSnIncreased BF and impaired insulin sensitivity are associated with increased concentrations of cardiovascular risk factors. Leptin seems to be involved in this elevation and emerges as a predictor of circulating fibrinogen concentrations.

Stem cells isolated from adipose tissue of obese patients show changes in their transcriptomic profile that indicate loss in stemcellness and increased commitment to an adipocyte-like phenotype

BackgroundThe adipose tissue is an endocrine regulator and a risk factor for atherosclerosis and cardiovascular disease when by excessive accumulation induces obesity. Although the adipose tissue is also a reservoir for stem cells (ASC) their function and “stemcellness” has been questioned. Our aim was to investigate the mechanisms by which obesity affects subcutaneous white adipose tissue (WAT) stem cells.ResultsTranscriptomics, in silico analysis, real-time polymerase chain reaction (PCR) and western blots were performed on isolated stem cells from subcutaneous abdominal WAT of morbidly obese patients (ASCmo) and of non-obese individuals (ASCn). ASCmo and ASCn gene expression clustered separately from each other. ASCmo showed downregulation of “stemness” genes and upregulation of adipogenic and inflammatory genes with respect to ASCn. Moreover, the application of bioinformatics and Ingenuity Pathway Analysis (IPA) showed that the transcription factor Smad3 was tentatively affected in obese ASCmo. Validation of this target confirmed a significantly reduced Smad3 nuclear translocation in the isolated ASCmo.ConclusionsThe transcriptomic profile of the stem cells reservoir in obese subcutaneous WAT is highly modified with significant changes in genes regulating stemcellness, lineage commitment and inflammation. In addition to body mass index, cardiovascular risk factor clustering further affect the ASC transcriptomic profile inducing loss of multipotency and, hence, capacity for tissue repair. In summary, the stem cells in the subcutaneous WAT niche of obese patients are already committed to adipocyte differentiation and show an upregulated inflammatory gene expression associated to their loss of stemcellness.

Disruption of the Leptin-Insulin Relationship in Obese Men 24 Hours after Laparoscopic Adjustable Silicone Gastric Banding

Background:The placement of a band to attain a tiny stomach pouch has been reported to produce early satiety in patients undergoing gastric banding. The adipocyte-derived hormone, leptin, has been shown to decrease both food intake and body weight. The aim of the present study was to assess the potential involvement of acute changes in leptin concentrations following laparoscopic adjustable silicone gastric banding (LASGB). Methods:The study groups comprised obese male patients undergoing bariatric surgery by LASGB and overweight men undergoing laparoscopic Nissen fundoplication (NFd). Blood was drawn before surgery and 24 hours postoperatively for glucose, insulin and leptin measurements. Results: In both experimental groups, a statistically significant decrease was observed in pre- and postsurgery glucose (LASGB 111 ± 8 vs 99 ± 6 mg/dl, P<0.01; NFd 107 ± 7 vs 98 ± 5 mg/d, P<0.01) and insulin concentrations (LASGB 39.8 ± 11.9 vs 32.9 ± 10.3 U/l, P<0.01; NFd 13.2 ± 3.3 vs 12.2 ± 2.9 U/l, P<0.05). However, no significant differences were observed when the percent change from pre-surgery values was analysed between both groups. Following surgery, an increase in leptin concentrations was observed in the LASGB group (23.5 ± 4.7 vs 37.5 ± 6.8 µg/l, P<0.001) whereas a small decrease was evident in the NFd patients (12.9 ± 4.6 vs 8.9 ± 2.2 µg/l, P<0.01). Conclusion: These findings strongly suggest that the short-term increase observed in plasma leptin concentrations following LASGB may play a key role in triggering an early satiety signal due to the modi fication of the gastrointestinal anatomy and physiology.

Paraganglioma extraadrenal localizado por PET y extirpado por vía laparoscópica

Resumen Los paragangliomas son tumores derivados del sistema neuroendocrino, muy poco frecuentes, cuya incidencia estimada es de alrededor de unos 0,2-0,5 casos por 100.000 habitantes/ano. El 60-70% de los paragangliomas son funcionantes, localizandose en su mayoria en el espacio retroperitoneal, sobre todo en las glandulas suprarrenales, constituyendo los feocromocitomas. Un porcentaje muy escaso tienen una localizacion extraadrenal. La mayoria son tumores unicos. El tratamiento de estos tumores consiste en la extirpacion quirurgica debido a la clinica, sobre todo de hipertension arterial (HTA), que producen y a la posibilidad de malignizacion. Presentamos el caso de un paciente diagnosticado por tomografia de emision de positrones (PET) de paraganglioma extraadrenal localizado en la confluencia de las venas cava y renal derecha, al que se realizo extirpacion del mismo mediante abordaje laparoscopico transabdominal.

Laparoscopic Treatment of Median Arcuate Ligament Syndrome: Analysis of Long-Term Outcomes and Predictive Factors

BackgroundLaparoscopic arcuate ligament release has been demonstrated a valid therapeutic option for arcuate ligament syndrome. Nevertheless, long-term follow-up and predictive factors have not been described for this treatment.MethodsClinical and surgical data and short- and long-term outcomes together with the impact of the degree of stenosis of the celiac trunk were analyzed in 13 consecutive patients who underwent laparoscopic arcuate ligament release between 2001 and 2013.ResultsThirteen patients (12xa0F/1xa0M) underwent surgery. The median age was 32xa0years old, and their mean body mass index was 20.7 (range 14.7–25). The 13 patients presented with intense postprandial abdominal pain. Ten cases were associated with weight loss. The median duration of symptoms was 24xa0months (range 2–240). Three patients presented symptoms associated with superior mesenteric artery syndrome. Median operative time was 120xa0min (range 90–240), and there were no conversions to open surgery. Median hospital stay was 3xa0days (range 2–14). Over a median follow-up of 117xa0months (range 45–185), nine patients had excellent results although two required endovascular procedures at 70 and 24xa0months after surgery. Four patients (30.7%) experienced poor outcomes. When we analyzed the impact of the degree of occlusion of the celiac trunk, we observed that in patients with severe occlusion (>u200970%), better results were obtained, with complete resolution of symptoms in 71% of cases.ConclusionLaparoscopic arcuate ligament release constitutes an excellent treatment for arcuate ligament syndrome. The degree of occlusion of the celiac trunk may be a factor predictive of long-term outcomes.