miR33a/miR33b* and miR122 as Possible Contributors to Hepatic Lipid Metabolism in Obese Women with Nonalcoholic Fatty Liver Disease.

Specific miRNA expression profiles have been shown to be associated with nonalcoholic fatty liver disease (NAFLD). We examined the correlation between the circulating levels and hepatic expression of miR122 and miR33a/b*, the key lipid metabolism-related gene expression and the clinicopathological factors of obese women with NAFLD. We measured miR122 and miR33a/b* expression in liver samples from 62 morbidly obese (MO), 30 moderately obese (ModO), and eight normal-weight controls. MiR122 and miR33a/b* expression was analyzed by qRT-PCR. Additionally, miR122 and miR33b* circulating levels were analyzed in 122 women. Hepatic miR33b* expression was increased in MO compared to ModO and controls, whereas miR122 expression was decreased in the MO group compared to ModO. In obese cohorts, miR33b* expression was increased in nonalcoholic steatohepatitis (NASH). Regarding circulating levels, MO patients with NASH showed higher miR122 levels than MO with simple steatosis (SS). These circulating levels are good predictors of histological features associated with disease severity. MO is associated with altered hepatic miRNA expression. In obese women, higher miR33b* liver expression is associated with NASH. Moreover, multiple correlations between miRNAs and the expression of genes related to lipid metabolism were found, that would suggest a miRNA-host gene circuit. Finally, miR122 circulating levels could be included in a panel of different biomarkers to improve accuracy in the non-invasive diagnosis of NASH.

Increased Circulating Levels of Alpha-Ketoglutarate in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) causes a wide spectrum of liver damage, ranging from simple steatosis to cirrhosis. However, simple steatosis (SS) and steatohepatitis (NASH) cannot yet be distinguished by clinical or laboratory features. The aim of this study was to assess the relationship between alpha-ketoglutarate and the degrees of NAFLD in morbidly obese patients. MATERIALS AND METHODS: We used a gas chromatography-quadruple time-of-flight-mass spectrometry analysis to quantify alpha-ketoglutarate in serum from normal-weight subjects (n = 30) and morbidly obese women (n = 97) with or without NAFLD. RESULTS: We found that serum levels of alpha-ketoglutarate were significantly higher in morbidly obese women than in normal-weight women. We showed that circulating levels of alpha-ketoglutarate were lower in lean controls and morbidly obese patients without NAFLD. We also found that alpha-ketoglutarate serum levels were higher in both SS and NASH than in normal liver of morbidly obese patients. However, there was no difference between SS and NASH. Moreover, we observed that circulating levels of alpha-ketoglutarate were associated with glucose metabolism parameters, lipid profile, hepatic enzymes and steatosis degree. In addition, diagnostic performance of alpha-ketoglutarate has been analyzed in NAFLD patients. The AUROC curves from patients with liver steatosis exhibited an acceptable clinical utility. Finally, we showed that the combination of biomarkers (AST, ALT and alpha-ketoglutarate) had the highest accuracy in diagnosing liver steatosis. CONCLUSION: These findings suggest that alpha-ketoglutarate can determine the presence of non-alcoholic fatty liver in morbidly obese patients but it is not valid a biomarker for NASH.

PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease.

Recent reports suggest a role for the Patatin-like phospholipase domain-containing protein 3 (PNPLA3) in the pathology of non-alcoholic fatty liver disease (NAFLD). Lipid deposition in the liver seems to be a critical process in the pathogenesis of NAFLD. The aim of the present work was to evaluate the association between the liver PNPLA3 expression, key genes of lipid metabolism, and the presence of NAFLD in morbidly obese women. We used real-time polymerase chain reaction (PCR) analysis to analyze the hepatic expression of PNPLA3 and lipid metabolism-related genes in 55 morbidly obese subjects with normal liver histology (NL, n = 18), simple steatosis (SS, n = 20), and non-alcoholic steatohepatitis (NASH, n = 17). Liver biopsies were collected during bariatric surgery. We observed that liver PNPLA3 expression was increased in NAFLD than in NL. It was also upregulated in SS than in NL. Interestingly, we found that the expression of PNPLA3 was significantly higher in severe than mild SS group. In addition, the expression of the transcription factors LXRα, PPARα, and SREBP2 was positively correlated with PNPLA3 liver expression. Regarding rs738409 polymorphism, GG genotype was positive correlated with the presence of NASH. In conclusion, our results show that PNPLA3 could be related to lipid accumulation in liver, mainly in the development and progression of simple steatosis.

Downregulation of de Novo Fatty Acid Synthesis in Subcutaneous Adipose Tissue of Moderately Obese Women.

The purpose of this work was to evaluate the expression of fatty acid metabolism-related genes in human adipose tissue from moderately obese women. We used qRT-PCR and Western Blot to analyze visceral (VAT) and subcutaneous (SAT) adipose tissue mRNA expression involved in de novo fatty acid synthesis (ACC1, FAS), fatty acid oxidation (PPARα, PPARδ) and inflammation (IL6, TNFα), in normal weight control women (BMI < 25 kg/m², n = 35) and moderately obese women (BMI 30-38 kg/m², n = 55). In SAT, ACC1, FAS and PPARα mRNA expression were significantly decreased in moderately obese women compared to controls. The downregulation reported in SAT was more pronounced when BMI increased. In VAT, lipogenic-related genes and PPARα were similar in both groups. Only PPARδ gene expression was significantly increased in moderately obese women. As far as inflammation is concerned, TNFα and IL6 were significantly increased in moderate obesity in both tissues. Our results indicate that there is a progressive downregulation in lipogenesis in SAT as BMI increases, which suggests that SAT decreases the synthesis of fatty acid de novo during the development of obesity, whereas in VAT lipogenesis remains active regardless of the degree of obesity.

Interleukin-17A Gene Expression in Morbidly Obese Women.

Data from recent studies conducted in rodent models and humans suggest that interleukin-17A (IL-17A) plays a role in the induction of inflammation in adipose tissue during obesity. The aim of this study was to assess the gene expression of IL-17A in adipose tissue of morbidly obese patients. We used RT-PCR to evaluate the expression of IL-17A and several adipo/cytokines in the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) of 10 normal-weight control women (BMI < 25 kg/m2) and 30 morbidly obese women (MO, BMI > 40 kg/m2). We measured serum levels of IL-17A and adipo/cytokines in MO and normal weight women. IL-17A expression was significantly higher in VAT than in SAT in MO patients (p = 0.0127). It was very low in normal-weight controls in both VAT and SAT tissues. We found positive correlations between IL-17A and IL-6, lipocalin-2 and resistin in VAT of MO patients. The circulating level of IL-17A was higher in the normal-weight group than the MO patients (p = 0.032), and it was significantly related to adiponectin and TNFRII levels. In conclusion, IL-17A expression in VAT is increased in morbidly obese women, which suggests a link between obesity and innate immunity in low-grade chronic inflammation in morbidly obese women.

Altered fatty acid metabolism-related gene expression in liver from morbidly obese women with non-alcoholic fatty liver disease.

Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate gene expression of different fatty acid (FA) metabolism-related genes in morbidly obese (MO) women with NAFLD. Liver expression of key genes related to de novo FA synthesis (LXRα, SREBP1c, ACC1, FAS), FA uptake and transport (PPARγ, CD36, FABP4), FA oxidation (PPARα), and inflammation (IL6, TNFα, CRP, PPARδ) were assessed by RT-qPCR in 127 MO women with normal liver histology (NL, n = 13), simple steatosis (SS, n = 47) and non-alcoholic steatohepatitis (NASH, n = 67). Liver FAS mRNA expression was significantly higher in MO NAFLD women with both SS and NASH compared to those with NL (p = 0.003, p = 0.010, respectively). Hepatic IL6 and TNFα mRNA expression was higher in NASH than in SS subjects (p = 0.033, p = 0.050, respectively). Interestingly, LXRα, ACC1 and FAS expression had an inverse relation with the grade of steatosis. These results were confirmed by western blot analysis. In conclusion, our results indicate that lipogenesis seems to be downregulated in advanced stages of SS, suggesting that, in this type of extreme obesity, the deregulation of the lipogenic pathway might be associated with the severity of steatosis.

Downregulation of lipogenesis and fatty acid oxidation in the subcutaneous adipose tissue of morbidly obese women.

OBJECTIVE: The aim of this study was to analyse the expression of crucial genes in fatty acid metabolism in visceral (VAT) and subcutaneous (SAT) adipose tissue samples from morbidly obese women. METHODS: The VAT and SAT expression of key genes in 145 morbidly obese women (MO, BMI > 40 Kg/m(2) ) and 18 normal weight control women by RT-PCR and Western Blot was analyzed. RESULTS: In SAT, the expression levels of the genes related to lipogenesis and fatty acid oxidation were significantly lower in MO than in controls. In VAT, most of the lipogenic genes studied had similar expression levels in MO and control cohort. Regarding inflammation, IL6 was significantly higher in MO in both tissues whereas TNFα mRNA expression was significantly higher only in VAT. CONCLUSIONS: Our results indicate that in morbidly obese patients, lipogenesis and fatty acid oxidation are downregulated in SAT, whereas in VAT these pathways are almost unchanged. By contrast, inflammation is induced in both adipose tissues. It is hypothesized that, in this type of extreme obesity, SAT works to limit any further development of fat mass, decreasing the expression of lipogenic and FA oxidative genes whereas VAT depot might have lost this capability.

Endocannabinoid receptors gene expression in morbidly obese women with nonalcoholic fatty liver disease.

BACKGROUND: Recent reports suggest a role for the endocannabinoid system in the pathology of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the relationship between liver expression of cannabinoid (CB) receptor subtypes, CB1 and CB2, in morbidly obese (MO) women with different histological stages of NAFLD. METHODS: We analysed hepatic CB1 and CB2 mRNA expression, and the expression of genes involved in lipid metabolism in 72 MO women, subclassified by liver histology into MO with normal liver (NL, n = 16), simple steatosis (SS, n = 28), and nonalcoholic steatohepatitis (NASH, n = 28) by enzyme-linked immunosorbent assay and RT-PCR. RESULTS: We found that CB1 mRNA expression was significantly higher in NASH compared with SS and correlated negatively with PPARα. Regarding CB2, CB2 mRNA expression correlated positively with ACC1, PPARγ, IL6, TNFα, resistin, and adiponectin. CONCLUSIONS: The increased expression of CB1 in NASH and the negative correlation with PPARα suggest a deleterious role of CB1 in NAFLD. Regarding CB2, its positive correlation with the anti-inflammatory molecule adiponectin and, paradoxically, with inflammatory genes suggests that this receptor has a dual role. Taken together, our results suggest that endocannabinoid receptors might be involved in the pathogenesis of NAFLD, a finding which justifies further study.

Clinical and adipocytokine changes after bariatric surgery in morbidly obese women.

OBJECTIVE: Recent studies report the effect of bariatric surgery on glycaemia control and prevention of type-2-diabetes in obese patients. This study is about the pathophysiological mechanisms associated to these changes. DESIGN AND METHODS: Circulating levels of receptors of tumor necrosis factor (TNF-RI, TNF-RII), visfatin, high molecular weight (HMW) adiponectin, and C reactive protein (CRP) in 30 morbidly obese women (body mass index, BMI>40 kg/m(2) ) and 60 normal-weight controls (BMI>25 kg/m(2) ) were analyzed. Morbidly obese were studied at three time-points: before surgery (baseline), and 6 and 12 months after. RESULTS: After surgery, the levels of TNF-RI, TNF-RII, visfatin, and CRP were significantly lower than its baseline levels, whereas HMW adiponectin was higher. Fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA2-IR) levels were markedly lower postoperatively. High density lipoproteins (HDL) moderately increased, and triglyceride levels had sharply decreased. The study of the predictive value of variables indicated that preoperative levels of TNF-RI and visfatin correlated positively with levels of glucose, insulin, glycosylated hemoglobin A1c, and HOMA2-IR postoperatively, whereas adiponectin levels correlated negatively. Baseline CRP levels negatively linked to HDL and TNF-RII positively to triglyceride. CONCLUSIONS: The preoperative profile with high levels of proinflammatory adipocytokines is linked to smaller improvements in glucose homeostasis and lipid factors. The use of a range of biomarkers may predict the level of metabolic changes following bariatric surgery.

Long-term changes in leptin, chemerin and ghrelin levels following different bariatric surgery procedures: Roux-en-Y gastric bypass and sleeve gastrectomy.

BACKGROUND: Different studies have evaluated changes in adipo/cytokine levels after bariatric surgery and have given conflicting results. The adipo/cytokines, leptin and chemerin, and the orexigenic hormone, ghrelin, have been shown to play a role in the regulation of metabolism and appetite. The aims of our study were to test the levels of these molecules after bariatric surgery and to compare the results between Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy. METHODS: We analysed circulating levels of chemerin, ghrelin and leptin in 30 morbidly obese women (body mass index of >40 kg/m2). Subjects were studied at three time points: baseline (before the surgery started), and after 6 and 12 months. RESULTS: After surgery, chemerin (baseline, 95.03 ± 23.79; after 12 months, 76.80 ± 21.51; p = 0.034) and leptin levels (baseline, 248.17 ± 89.16; after 12 months, 63.85 ± 33.48; p < 0.001) were significantly lower than their baseline levels, whereas ghrelin was higher (baseline, 0.87 ± 0.38; after 12 months, 1.08 ± 0.31; p = 0.010). Fasting glucose, insulin and homeostasis model assessment of insulin resistance levels were markedly lower postoperatively. High-density lipoprotein levels moderately increased and triglyceride levels sharply decreased. There were no differences between the types of bariatric surgery in terms of weight reduction, general metabolic state or adipo/cytokine levels after surgery. CONCLUSIONS: Our study demonstrates a marked decrease in fasting leptin and chemerin levels, and an increase in ghrelin levels, after bariatric surgery-induced weight loss, independently of the type of surgery performed. Further studies are needed on the interrelation between the changes in the circulating levels of these molecules and the efficacy of the bariatric surgery procedures to induce the beneficial metabolic changes and to sustain body weight loss.

Retinol binding protein-4 circulating levels were higher in nonalcoholic fatty liver disease vs. histologically normal liver from morbidly obese women.

OBJECTIVE: We aimed to analyze the retinol binding protein-4 (RBP4) messenger RNA (mRNA) expression profiles in adipose tissues and liver of morbidly obese (MO) women with or without nonalcoholic fatty liver disease (NAFLD), and to study the relationships with other pro- and anti-inflammatory adipokines in vivo and in vitro. DESIGN AND METHODS: We performed a cross-sectional analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and liver samples from four lean and 45 MO women with or without NAFLD by enzyme-linked immunosorbent assay and real-time reverse transcription-PCR. We also studied RBP4 expression in HepG2 hepatocytes under various inflammatory stimuli. RESULTS: Circulating RBP4 levels were higher in MO women, and specifically, in MO subjects with NAFLD compared with normal liver controls (lean and MO). RBP4 liver expression was higher in nonalcoholic steatohepatitis (NASH)-moderate/severe than in NASHmild. Overall RBP4 gene expression was higher in liver than in adipose tissues. Among them, the higher expression corresponded to SAT. VAT expression was lower in the MO cohort. In HepG2, RBP4 mRNA expression was reduced by tumor necrosis factor (TNF)-α and increased by adiponectin treatment. CONCLUSIONS: The results obtained in MO women with NAFLD, brings up the use of RBP4 and other adipokines as a panel of noninvasive molecular biomarkers when NAFLD is suspected. Further studies are needed with other obesity groups.

Plasma visfatin levels and gene expression in morbidly obese women with associated fatty liver disease.

OBJECTIVES: The few studies on the physiopathological role of visfatin in morbid obesity and the related metabolic diseases have led us to examine visfatin levels and its liver gene expression in morbidly obese women with non-alcoholic fatty liver disease (NAFLD). DESIGN AND METHODS: We examined the circulating levels of visfatin by ELISA in serum samples from 95 morbidly obese women (MO) (BMI>40 kg/m(2)) who underwent bariatric surgery and 38 normal weight control women (BMI<25 kg/m(2)). We analysed visfatin liver and adipose tissue mRNA expression by RT-PCR. We evaluated the circulating levels and gene expression of adiponectin, resistin, RBP4, TNFα, IL6 and CRP. RESULTS: Serum visfatin was significantly higher in MO compared with controls, and also in MO with NAFLD was significantly higher than MO with normal liver. We found that NAFLD diabetic patients presented similar serum visfatin levels than non-diabetic. Serum visfatin correlated with IL6 (r=0.496; p<0.001) and CRP levels (r=0.241; p=0.049). Liver visfatin expression was significantly higher in MO compared to controls and was also significantly higher in MO with NAFLD than in MO with normal liver. Visfatin liver expression correlated positively with resistin (r=0.436, p=0.018) and TNFα expression (r=0.328, p=0.028). Visfatin expression in adipose tissues was similar among the MO groups analysed. CONCLUSION: Serum visfatin and its liver expression are higher in MO women with NAFLD, irrespective of the presence of diabetes. Serum visfatin and its liver expression correlate positively with pro-inflammatory factors. These findings suggest that visfatin may be a molecule related with fat inflammation in morbid obesity and fatty liver disease.

Increased levels and adipose tissue expression of visfatin in morbidly obese women: the relationship with pro-inflammatory cytokines.

OBJECTIVE: The controversial results on the physiopathological role of visfatin led us to examine both circulating visfatin levels and gene expression in visceral (VAT) and subcutaneous fat (SAT) in a homogeneous group of morbidly obese women. DESIGN, PATIENTS AND MEASUREMENTS: We analysed circulating levels of several adipo/cytokines in 133 Spanish women: 40 lean (C) [body mass index (BMI) < 25 kg/m(2) ] and 93 morbidly obese (MO) (BMI > 40 kg/m(2) ). In the MO group, we found 31 diabetic and 62 nondiabetic subjects. We obtained follow-up blood samples at 6 and 12 months after bariatric surgery from 30 MO patients. We determined the circulating levels of visfatin, adiponectin, interleukin-6 (IL6), C-reactive protein (CRP), resistin and tumour necrosis factor-α (TNFα) by ELISA, and visfatin, adiponectin, IL6, resistin and TNFα gene expression in SAT and VAT by real-time RT-PCR. RESULTS: Circulating visfatin levels were higher in MO women compared with lean controls (C = 1·43 ± 0·14 µg/l, MO = 3·60 ± 0·29 µg/l, P < 0·001). After bariatric surgery-induced weight loss, visfatin levels were reduced significantly over 12 months. Visfatin expression in SAT and VAT was similar, but significantly higher in MO compared to C and independent of the presence of diabetes mellitus. Circulating visfatin levels were positively related to IL6 and CRP levels. Visfatin gene expression in VAT and SAT was strongly related to IL6 and TNFα expression. CONCLUSION: In a homogeneous cohort of morbidly obese women, our findings show that visfatin has a strong relationship with pro-inflammatory factors in severe obesity.

Upregulation of lipocalin 2 in adipose tissues of severely obese women: positive relationship with proinflammatory cytokines.

Because the role of lipocalin 2 (LCN2) in morbid obesity is still not well defined, the aim of this study was to evaluate the circulating levels and the expression of LCN2 in visceral (VAT) and subcutaneous adipose tissue (SAT) in severely obese (SO) women. We also analyzed its relationship with inflammatory cytokines in the same subjects. The study comprised 90 white women, 39 of whom were lean controls (BMI ≤25 kg/m(2)) and 51 SO (BMI ≥40 kg/m(2)). Both circulating and adipose tissue levels of LCN2 were quantified by enzyme-linked immunosorbent assays. LCN2 mRNA levels from VAT and SAT were assessed by real-time reverse transcriptase-PCR (n = 60). LCN2 serum levels were significantly higher in the SO women than in the lean controls (P = 0.042), and were found to be strongly correlated with tumor necrosis factor receptor I (TNFR1) circulating levels. In the SO cohort, LCN2 serum levels were also associated with higher BMI values, but not with the homeostasis model assessments of insulin resistance (HOMA2-IR). LCN2 mRNA expression was markedly higher in SO women than in lean women in both VAT (P = 0.043) and SAT (P = 0.031). In SAT, LCN2 was negatively correlated with adiponectin and adiponectin receptor-2 expression, and positively with interleukin-6 (IL-6) expression. A strong positive correlation was also found between LCN2 expression and the mean diameter of adipocytes in VAT. Our results revealed that the circulating level of LCN2 is associated with obesity and BMI. LCN2 mRNA is over-expressed in adipose tissue from SO subjects. Finally, the expression of LCN2 is strongly related to an expression profile of proinflammatory cytokines but not to insulin resistance in nondiabetic SO women.

New adipokines vaspin and omentin. Circulating levels and gene expression in adipose tissue from morbidly obese women.

BACKGROUND: Vaspin and omentin are recently described molecules that belong to the adipokine family and seem to be related to metabolic risk factors. The objectives of this study were twofold: to evaluate vaspin and omentin circulating levels and mRNA expression in subcutaneous and visceral adipose tissues in non-diabetic morbidly obese women; and to assess the relationship of vaspin and omentin with anthropometric and metabolic parameters, and other adipo/cytokines. DESIGN: We analysed vaspin and omentin circulating levels in 71 women of European descent (40 morbidly obese [BMI≥40 kg/m2] and 31 lean [BMI≤25]). We assessed vaspin and omentin gene expression in paired samples of visceral and subcutaneous abdominal adipose tissue from 46 women: 40 morbidly obese and 6 lean. We determined serum vaspin and plasma omentin levels with an Enzyme-Linked Immunosorbent Assay and adipose tissue mRNA expression by real time RT-PCR. RESULTS: Serum vaspin levels in the morbidly obese were not significantly different from those in controls. They correlated inversely with levels of lipocalin 2 and interleukin 6. Vaspin mRNA expression was significantly higher in the morbidly obese, in both subcutaneous and visceral adipose tissue.Plasma omentin levels were significantly lower in the morbidly obese and they correlated inversely with glucidic metabolism parameters. Omentin circulating levels, then, correlated inversely with the metabolic syndrome (MS). Omentin expression in visceral adipose tissue was significantly lower in morbidly obese women than in controls. CONCLUSIONS: The present study indicates that vaspin may have a compensatory role in the underlying inflammation of obesity. Decreased omentin circulating levels have a close association with MS in morbidly obese women.

FABP 4 is associated with inflammatory markers and metabolic syndrome in morbidly obese women.

OBJECTIVE: The adipocyte/macrophage fatty acid-binding protein 4 (FABP4) has been described as a biomarker for adiposity and metabolic syndrome (MS). The aims of this study were to assess the relationship between FABP4 and inflammatory cytokines related to obesity, and to evaluate FABP4 mRNA expression in visceral and subcutaneous adipose tissue in non-diabetic morbidly obese women versus healthy lean women. METHODS: We analyzed circulating levels of FABP4 in 81 Spanish women: 38 lean (body mass index (BMI)<25 kg/m(2)) and 43 morbidly obese (BMI>40 kg/m(2)). We took 30 follow-up blood samples at 6 and 12 months after bariatric surgery. We assessed FABP4 gene expression in samples of subcutaneous abdominal and visceral adipose tissue. Adipose tissue mRNA expression was determined by real-time RT-PCR. RESULTS: In morbidly obese women, plasma FABP4 levels were significantly higher than in non-obese patients. These levels positively correlated with BMI, homeostasis model assessment of insulin resistance (HOMA2-IR), and plasma glucose and insulin levels. Post-operative FABP4 levels decreased by a maximum of 30% after 12 months. We also found an inverse association between FABP4 and adiponectin levels, and positive correlations between FABP4 and circulating leptin, tumor necrosis factor (TNF) receptors, C-reactive protein (CRP) and interleukin 6 levels. Linear regression analysis revealed that FABP4 was more closely related to HOMA2-IR than adiponectin, CRP, TNF-RI, or leptin. Furthermore, high circulating FABP4 levels were associated with the presence of MS. FABP4 mRNA expression in visceral adipose tissue was related to its circulating levels in morbidly obese women. CONCLUSIONS: Our results indicate that serum FABP4 is associated with inflammatory factors related to obesity and MS in non-diabetic morbidly obese women.

Immunohistochemical analysis of paraoxonases-1 and 3 in human atheromatous plaques.

BACKGROUND: The paraoxonase (PON) enzyme family comprising PON1, PON2 and PON3 are antioxidant enzymes that degrade bioactive oxidised lipids and are thus antiatherogenic. MATERIALS AND METHODS: We investigated the localisation of the PON proteins during the development of atherosclerosis by immunohistochemical analysis. RESULTS: In normal aortas, PON1 and PON3 were localised to smooth muscle cells (SMC) and endothelial cells. PON3 staining was stronger than that of PON1. During atherosclerosis development, SMC staining for PON1 and PON3 was greatly reduced, while macrophage staining for both proteins increased with PON1 predominating. Macrophage staining for PON1 and PON3 was significantly and positively related to the amount of aortic inflammation (both P<0·001). CONCLUSIONS: Our data add support to the growing body of evidence for a cellular protective effect of PON1 and PON3 against the proinflammatory/proatherosclerotic effects of lipid peroxidation.

Anti-inflammatory profile of FTO gene expression in adipose tissues from morbidly obese women.

BACKGROUND: The fat mass and obesity associated (FTO) gene has been found to contribute to the risk of obesity in humans, but the function and regulation of FTO mRNA expression in adipose tissues remain to be clarified. Our aims were to assess the FTO gene expression in subcutaneous and visceral adipose tissues from morbidly obese women and its relation with obesity, insulin resistance indices, and most importantly, to obesity-related inflammatory markers. METHODS: Paired subcutaneous and visceral fat were excised from 33 morbidly obese women and 12 control women who underwent bariatric surgery by laparoscopic gastric by-pass and elective surgery respectively. Adipose tissue mRNA expression was determined by real time RT-PCR. RESULTS: FTO mRNA expression in visceral adipose tissue (VAT) was significantly higher than in subcutaneous adipose tissue (SAT) from obese but not control patients. SAT FTO expression was reduced in obese women compared to control subjects. It correlated negatively with BMI and insulin resistance indices. FTO expression in SAT was positively related to both circulating and mRNA levels of adiponectin, to adiponectin receptor and to PPAR-δexpression, but negatively with IL-6 gene expression and with circulating levels of leptin. FTO in VAT was also positively correlated with adiponectin, adiponectin receptor and PPAR-δ mRNA expression. CONCLUSION: FTO expression in subcutaneous adipose tissue negatively correlates with obesity and insulin resistance. On the other hand, FTO presents a positive association with the expression of adiponectin, an anti-inflammatory adipokine, and with PPAR-δ in both adipose tissues. Taken together, our results suggest that FTO is associated with an anti-inflammatory behaviour in morbid obesity.

Cirugía experimental y obesidad mórbida / Experimental surgery and morbid obesity

Se lleva a cabo un estudio de la evolución de la cirugía bariátrica experimental en animales de laboratorio y se determinan las necesidades actuales en este campo para el seguimiento de nuevas líneas de investigación.Se hace una revisión de los trabajos experimentales sobre cirugía de la obesidad mórbida desde la última mitad del siglo xx, según las diferentes técnicas existentes (malbsortivas, restrictivas, mixtas y experimentales). Las fuentes de información utilizadas han sido las búsquedas en la National Library of Medicine (PubMed).Se observa una clara tendencia a la utilización de animales de gran tamaño (cerdos) para el perfeccionamiento técnico, en especial de la laparoscopia.Una segunda dirección en la experimentación animal se centra en determinar un nexo metabolicoquirúrgico, que determinaría una mejoría de las comorbilidades. Por último, una tercera línea de investigación estaría centrada en la manipulación de la ingesta a partir de control central y vagal.Se necesitan estudios en que se combine la cirugía experimental en animales de laboratorio con los mecanismos que determinan su fisiopatología, su metabolismo y los que regulan su ingesta, tanto en las técnicas que están aplicadas a la práctica clínica como en las que están en fase experimental. Es necesario que los trabajos se realicen con animales obesos para conocer con exactitud los patrones metabólicos y evitar conclusiones erróneas sobre los mecanismos de la pérdida de peso (AU)