Curcumin as a hepatoprotective agent against chemotherapy-induced liver injury.

Despite significant advances in cancer therapeutics, chemotherapy remains the cornerstone of treatment for many tumors. Importantly, however, chemotherapy-induced toxicity, including hepatotoxicity, can lead to the interruption or discontinuation of potentially effective therapy. In recent years, special attention has been paid to the search for complementary therapies to mitigate chemotherapy-induced toxicity. Although there is currently a lack of specific interventions to mitigate or prevent hepatotoxicity in chemotherapy-treated patients, the polyphenol compound curcumin has emerged as a potential strategy to overcome this adverse effect. Here we review, firstly, the molecular and physiological mechanisms and major risk factors of chemotherapy-induced hepatotoxicity. We then present an overview of how curcumin has the potential to mitigate hepatotoxicity by targeting specific molecular mechanisms. Hepatotoxicity is a well-described side effect of cytotoxic drugs that can limit their clinical application. Inflammation and oxidative stress are the most common mechanisms involved in hepatotoxicity. Several studies have shown that curcumin could prevent and/or palliate chemotherapy-induced liver injury, mainly due to its anti-inflammatory, antioxidant, antifibrotic and hypolipidemic properties. Further clinical investigation using bioavailable curcumin formulations is warranted to demonstrate its efficacy as an hepatoprotective agent in cancer patients.

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.

Adjustable Gastric Banding Conversion to One Anastomosis Gastric Bypass: Data Analysis of a Multicenter Database.

INTRODUCTION: One anastomosis gastric bypass (OAGB) has been proposed as a rescue technique for laparoscopic adjustable gastric banding (LAGB) poor responders. AIM: We sought to analyze, complications, mortality, and medium-term weight loss results after LAGB conversion to OAGB. METHODS: Data analysis of an international multicenter database. RESULTS: One hundred eighty-nine LAGB-to-OAGB operations were retrospectively analyzed. Eighty-seven (46.0%) were converted in one stage. Patients operated on in two stages had a higher preoperative body mass index (BMI) (37.9 vs. 41.3 kg/m2, p = 0.0007) and were more likely to have encountered technical complications, such as slippage or erosions (36% vs. 78%, p < 0.0001). Postoperative complications occurred in 4.8% of the patients (4.6% and 4.9% in the one-stage and the two-stage group, respectively). Leak rate, bleeding episodes, and mortality were 2.6%, 0.5%, and 0.5%, respectively. The final BMI was 30.2 at a mean follow-up of 31.4 months. Follow-up at 1, 3, and 5 years was 100%, 88%, and 70%, respectively. CONCLUSION: Conversion from LAGB to OAGB is safe and effective. The one-stage approach appears to be the preferred option in non-complicate cases, while the two-step approach is mostly done for more complicated cases.

The Complex Relationship Between Microbiota, Immune Response and Creeping Fat in Crohn's Disease.

In the last decade, there has been growing interest in the pathological involvement of hypertrophic mesenteric fat attached to the serosa of the inflamed intestinal segments involved in Crohn's disease [CD], known as creeping fat. In spite of its protective nature, creeping fat harbours an aberrant inflammatory activity which, in an already inflamed intestine, may explain why creeping fat is associated with a greater severity of CD. The transmural inflammation of CD facilitates the interaction of mesenteric fat with translocated intestinal microorganisms, contributing to activation of the immune response. This may be not the only way in which microorganisms alter the homeostasis of this fatty tissue: intestinal dysbiosis may also impair xenobiotic metabolism. All these CD-related alterations have a functional impact on nuclear receptors such as the farnesoid X receptor or the peroxisome proliferator-activated receptor γ, which are implicated in regulation of the immune response, adipogenesis and the maintenance of barrier function, as well as on creeping fat production of inflammatory-associated cells such as adipokines. The dysfunction of creeping fat worsens the inflammatory course of CD and may favour intestinal fibrosis and fistulizing complications. However, our current knowledge of the pathophysiology and pathogenic role of creeping fat is controversial and a better understanding might provide new therapeutic targets for CD. Here we aim to review and update the key cellular and molecular alterations involved in this inflammatory process that link the pathological components of CD with the development of creeping fat.

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.

Seasonal variation of body weight loss after bariatric surgery.

Seasonal variations have been described in humans in several variables such as sleep, mood, appetite, food preferences, or body weight. We hypothesized that these variations could also influence the decrease in body weight rate in patients submitted to body weight loss interventions. Thus, here we tested the variations of weight loss according to the time of the year the surgery took place in a group patients (n = 1322) submitted to bariatric surgery in the Hospital Universitari de la Vall d'Hebron in Barcelona (geographical coordinates: 41°25'41″N 2°8'32″E). For the analysis, the percentage of total body weight loss (%TWL), excess body weight loss (%EWL) and percentage of body mass index loss (%BMIL) were calculated at 3 (n = 1255), 6 (n = 1172), 9 (n = 1002), and 12 months (n = 1076) after surgery. For %EWL and %BMIL a statistically significant seasonal variation was detected when the variables were calculated at 3 months, but not at the other times, with more weight loss in summer-fall. However, seasonal variations were not detected for %TWL (p = 0.09). The mean amplitude of the seasonal rhythm for %EWL was of 1.8%, while for the rhythm of %BMIL was 0.7%. Moreover, a second peak was detected in January-February modulating the seasonal rhythm of the two variables. Results confirm seasonal variations in humans and indicate that short term responses to weight loss can be modulated by the time of year.

Seasonal variations of changes in lipid and glucidic variables after bariatric surgery.

Seasonality is a phenomenon that is characterized by changes over the year in sleep, mood, behaviour, appetite and body weight. In humans, seasonal variations have been found in certain variables, such as lipid variables and body mass index. We hypothesize that this rhythm could influence the expected variation of the levels of biochemical variables in cases of body weight loss. Thus, the goal of this study was to observe whether the time of year in which bariatric surgery (BS) took place modulated the changes in several variables related to glucidic and lipid metabolism. Blood samples were obtained from 24 women and 10 men before BS and 1 and 3 months after BS. We calculated the percentage of variation that occurred for each individual and for each variable as a function of the time of the year. Data were adjusted to a 12-month period sinusoidal curve, with significance being set at p < 0.05. The results showed that almost all of the studied variables changed due to the BS according to a seasonal rhythm. Most of the variables showed a decrease that was most prominent in winter. In the cases of body mass index (BMI), adrenocorticotropin hormone (ACTH), and cortisol, the highest variation occurred in winter. Insulin and cholesterol in high-density lipoproteins (cHLD) variations were higher in springtime. Glucose variation showed a decrease after surgery with acrophase in summer-fall and plasminogen activator inhibitor-1 (PAI-1) and homeostatic model assessment-insulin resistance (HOMA-IR) in spring-summer. Ghrelin levels showed increases with a rhythm of variation with an acrophase in summer-fall. The seasonal rhythm found in this study fits nearly with the inverse of the endogenous circannual rhythm of the variables studied. The time of the year when the highest variation takes place is related to the circannual rhythm of the variable. The results agree with the manifestation of seasonal rhythm in human biochemical variables, which are reflected in the responses to weight loss after BS.

Roux-en-Y gastric bypass, sleeve gastrectomy, or one anastomosis gastric bypass as rescue therapy after failed adjustable gastric banding: a multicenter comparative study.

BACKGROUND: To date, laparoscopic adjustable gastric banding remains the third most commonly performed surgical procedure for weight loss. Some patients fail to get acceptable outcomes and undergo revisional surgery at rates ranging from 7% to 60%. Roux-en-Y gastric bypass (RYGB), one anastomosis gastric bypass (OAGB), and sleeve gastrectomy (SG) are among the most common salvage options for failed laparoscopic adjustable gastric banding. OBJECTIVE: To compare the outcomes of converting failed laparoscopic adjustable gastric banding to RYGB, OAGB, or SG. METHODS: Data collected from 7 experienced bariatric centers around the world were retrospectively collected, reviewed, and analyzed. Final body mass index (BMI), change in BMI, percentage excess BMI loss, and major complications with particular attention to leaks, hemorrhage, and mortality were reported. RESULTS: Of 1219 patients analyzed, 74% underwent RYGB, 16% underwent OAGB, and 10% underwent SG after banding failure. The mean age was 38 years (±10 yr), and 82% of patients were women. The mean follow-up was 33 months. The follow-up rate was 100%, 87%, and 52% at 1, 3, and 5 years, respectively. At the latest follow-up, percentage excess BMI loss >50% was achieved by 75% of RYGB, 85% of OAGB, and 67% of SG patients. Postoperative complications occurred in 13% of patients after RYGB, 5% after OAGB, and 15% after SG. CONCLUSION: Our data show that it is possible to achieve or maintain significant weight loss with an acceptable complication rate with all 3 surgical options.

LXR-dependent regulation of macrophage-specific reverse cholesterol transport is impaired in a model of genetic diabesity.

Diabesity and fatty liver have been associated with low levels of high-density lipoprotein cholesterol, and thus could impair macrophage-specific reverse cholesterol transport (m-RCT). Liver X receptor (LXR) plays a critical role in m-RCT. Abcg5/g8 sterol transporters, which are involved in cholesterol trafficking into bile, as well as other LXR targets, could be compromised in the livers of obese individuals. We aimed to determine m-RCT dynamics in a mouse model of diabesity, the db/db mice. These obese mice displayed a significant retention of macrophage-derived cholesterol in the liver and reduced fecal cholesterol elimination compared with nonobese mice. This was associated with a significant downregulation of the hepatic LXR targets, including Abcg5/g8. Pharmacologic induction of LXR promoted the delivery of total tracer output into feces in db/db mice, partly due to increased liver and small intestine Abcg5/Abcg8 gene expression. Notably, a favorable upregulation of the hepatic levels of ABCG5/G8 and NR1H3 was also observed postoperatively in morbidly obese patients, suggesting a similar LXR impairment in these patients. In conclusion, our data show that downregulation of the LXR axis impairs cholesterol transfer from macrophages to feces in db/db mice, whereas the induction of the LXR axis partly restores impaired m-RCT by elevating the liver and small intestine expressions of Abcg5/g8.

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.

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.

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.

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.

Bariatric surgery in morbidly obese patients improves the atherogenic qualitative properties of the plasma lipoproteins.

OBJECTIVE: The purpose of this study was to evaluate the effect of weight loss induced in morbidly obese subjects by Roux-en-Y gastric bypass bariatric surgery on the atherogenic features of their plasma lipoproteins. METHODS: Twenty-one morbidly obese subjects undergoing bariatric surgery were followed up for up to 1 year after surgery. Plasma and lipoproteins were assayed for chemical composition and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity. Lipoprotein size was assessed by non-denaturing polyacrylamide gradient gel electrophoresis, and oxidised LDL by ELISA. Liver samples were assayed for mRNA abundance of oxidative markers. RESULTS: Lipid profile analysis revealed a reduction in the plasma concentrations of cholesterol and triglycerides, which were mainly associated with a significant reduction in the plasma concentration of circulating apoB-containing lipoproteins rather than with changes in their relative chemical composition. All patients displayed a pattern A phenotype of LDL subfractions and a relative increase in the antiatherogenic plasma HDL-2 subfraction (>2-fold; P < 0.001). The switch towards predominantly larger HDL particles was due to an increase in their relative cholesteryl ester content. Excess weight loss also led to a significant decrease in the plasma concentration of oxidised LDL (∼-25%; P < 0.01) and in the total Lp-PLA2 activity. Interestingly, the decrease in plasma Lp-PLA2 was mainly attributed to a decrease in the apoB-containing lipoprotein-bound Lp-PLA2. CONCLUSION: Our data indicate that the weight loss induced by bariatric surgery ameliorates the atherogenicity of plasma lipoproteins by reducing the apoB-containing Lp-PLA2 activity and oxidised LDL, as well as increasing the HDL-2 subfraction.

Soluble CD40 ligand in morbidly obese patients: effect of body mass index on recovery to normal levels after gastric bypass surgery.

IMPORTANCE: In recent years, the CD40/CD40L system has been implicated in the pathophysiology of severe chronic inflammatory diseases. Recently, obesity has been described as a low chronic inflammatory disease, so this system could also be involved in the inflammatory process. OBJECTIVE: To study soluble CD40 ligand (sCD40L) and other factors implicated in coagulation (plasminogen activator inhibitor 1, antithrombin III, and fibrinogen) and inflammation (C-reactive protein) in patients with morbid obesity and different body mass indexes (BMIs) (calculated as weight in kilograms divided by height in meters squared), before and after weight loss induced by bariatric surgery. DESIGN: Plasma samples were obtained before and after a bariatric surgery intervention. Several inflammatory markers were then studied (sCD40L, plasminogen activator inhibitor 1, antithrombin III, and C-reactive protein). The values obtained were compared with a control group of nonobese persons. PARTICIPANTS: Thirty-four morbidly obese patients undergoing gastric bypass surgery and 22 normal-weight controls matched for age and sex. INTERVENTIONS: A Roux-en-Y gastric bypass was performed in morbidly obese patients. MAIN OUTCOME MEASURES: Levels of sCD40L, plasminogen activator inhibitor 1, antithrombin III, fibrinogen, and C-reactive protein 12 months after bariatric surgery. RESULTS: Obese men showed a tendency for decreased plasma sCD40L levels 1 year after surgery (mean [SEM], 246.5 [70.4] pg/mL before vs 82.2 [23.2] pg/mL after surgery; P < .05), whereas there were not any significant changes in obese women (285.9 [67.5] pg/mL before vs 287.0 [56.9] pg/mL after surgery). Levels of the other markers studied decreased significantly with weight loss in both sexes. However, all other studied markers tend to have higher concentrations in patients with higher BMIs, except for sCD40L, which tended to have lower concentrations in patients with BMIs higher than 55. The decreases with weight loss were lower with higher BMIs for all measurements, except for antithrombin III. CONCLUSIONS AND RELEVANCE: Increased BMI, but not sex, influences recovery to normal levels for the markers studied, possibly indicating a worse prognosis.