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OBJECTIVE To determine the potential use of baseline circulating succinate to predict type 2 diabetes remission after bariatric surgery. RESEARCH DESIGN AND METHODS Forty-five obese patients with diabetes were randomly assigned to Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), or laparoscopic greater curvature plication. Anthropometric parameters were evaluated, and a complete biochemical analysis including circulating serum succinate concentrations was performed at baseline and 1 year after surgery. The results were externally validated in a second cohort including 88 obese patients with diabetes assigned to RYGB or SG based on clinical criteria. RESULTS Succinate baseline concentrations were an independent predictor of diabetes remission after bariatric surgery. Patients achieving remission after 1 year had lower levels of baseline succinate (47.8 [37.6-64.6] mu mol/L vs. 64.1 [52.5-82.9] mu mol/L; P = 0.018). Moreover, succinate concentrations were significantly decreased 1 year after surgery (58.9 [46.4-82.4] mu mol/L vs. 46.0 [35.8-65.3] mu mol/L, P = 0.005). In multivariate analysis, the best logistic regression model showed that baseline succinate (odds ratio [OR] 11.3, P = 0.031) and the type of surgery (OR 26.4, P = 0.010) were independently associated with remission. The C-statistic for this model was 0.899 (95% CI 0.809-0.989) in the derivation cohort, which significantly improved the prediction of remission compared with current available scores, and 0.729 (95% CI 0.612-0.846) in the validation cohort. Interestingly, patients had a different response to the type of surgery according to baseline succinate, with significant differences in remission rates. CONCLUSIONS Circulating succinate is reduced after bariatric surgery. Baseline succinate levels have predictive value for diabetes remission independently of previously described presurgical factors and improve upon the current available scores to predict remission.

Context: Microbiota perturbations seem to exert modulatory effects on emotional behavior, stress-, and pain-modulation systems in adult animals; however, limited information is available in humans. Objective: To study potential relationships among the gut metagenome, brain microstructure, and cognitive performance inmiddle-aged, apparently healthy, obese and nonobese subjects after weight changes. Design: This is a longitudinal study over a 2-year period. Setting: A tertiary public hospital. Patients or Other Participants: Thirty-five (18 obese) apparently healthy subjects. Intervention(s): Diet counseling was provided to all subjects. Obese subjects were followed every 6 months. Main Outcome Measure(s): Brain relaxometry (using magnetic resonance R2*), cognitive performance (by means of cognitive tests), and gut microbiome composition (shotgun). Results: R2* increased in both obese and nonobese subjects, independent of weight variations. Changes in waist circumference, but not in body mass index, were associated with brain iron deposition (R2*) in the striatum, amygdala, and hippocampus in parallel to visual-spatial constructional ability and circulating beta amyloid A beta 42 levels. These changes were linked to shifts in gut microbiome in which the relative abundance of bacteria belonging to Caldiserica and Thermodesulfobacteria phyla were reciprocally associated with raised R2* in different brain nuclei. Of note, the increase in bacteria belonging to Tenericutes phylum was parallel to decreased R2* gain in the striatum, serum Ab42 levels, and spared visual-spatial constructional ability. Interestingly, metagenome functions associated with circulating and brain iron stores are involved in bacterial generation of siderophores. Conclusions: Changes in the gut metagenome are associated longitudinally with cognitive function and brain iron deposition.

Objective: Lipopolysaccharide binding protein ( LBP) is part of a family of structurally and functionally related lipid transfer proteins. This study aimed to investigate the associations of LBP with the lipid composition of human adipose tissue. Methods: Lipidomic analysis was performed in whole adipose tissue. To validate the associations found, LBP was knocked down ( KD) in 3T3-L1 adipocytes, and lipidomic profile was evaluated by nontargeted lipidomics. Results: LBP gene expression was negatively associated with phosphatidylcholine, phosphatidylserine, and sphingomyelin relative abundance in vivo. LBP expression was also decreased in those samples with the highest docosahexanoic content, implicated in the resolution of inflammation. The KD of LBP ( by similar to 70%) led to sharp changes in the lipidome of adipocytes. Of note, specific plasmalogen species PE( O-16:0/22:5), PE(38: 2), odd chain glycerolipids, and cholesteryl linoleate were upregulated by LBP KD. In contrast, GM3 gangliosides, several ceramides, a triacylglycerol potentially containing arachidonate, and cholesteryl palmitate were downregulated by LBP KD. Conclusions: LBP seems to play a role in the regulation of lipid composition of adipose tissue linked to resilience to inflammation.

CONTEXT: Human placenta exhibits a specific microRNA (miRNA) expression pattern. Some of these miRNAs are dysregulated in pregnancy disorders such as preeclampsia and intrauterine growth restriction and are potential biomarkers for these pathologies. OBJECTIVE: To study the placental miRNA profile in pregnant women with pregestational overweight/obesity (preOB) or gestational obesity (gestOB) and explore the associations between placental miRNAs dysregulated in maternal obesity and prenatal and postnatal growth. METHODS: TaqMan Low Density Arrays and real-time polymerase chain reaction were used to profile the placental miRNAs in 70 pregnant women (20 preOB, 25 gestOB, and 25 control). Placentas and newborns were weighed at delivery, and infants were weighed at 1, 4, and 12 months of age. RESULTS: Eight miRNAs were decreased in placentas from preOB or gestOB (miR-100, miR-1269, miR-1285, miR-181, miR-185, miR-214, miR-296, and miR-487) (all P < 0.05). Among them, miR-100, miR-1285, miR-296, and miR-487 were associated with maternal metabolic parameters (all P < 0.05) and were predictors of lower birth weight (all P < 0.05; R2 > 30%) and increased postnatal weight gain (all P < 0.05; R2 > 20%). In silico analysis showed that these miRNAs were related to cell proliferation and insulin signaling pathways. miR-296 was also present in plasma samples and associated with placental expression and prenatal and postnatal growth parameters (all P < 0.05). CONCLUSIONS: We identified a specific placental miRNA profile in maternal obesity. Placental miRNAs dysregulated in maternal obesity may be involved in mediation of growth-promoting effects of maternal obesity on offspring and could be used as early markers of prenatal and postnatal growth.

Purpose Increased cardiovascular (CV) risk persists in Cushing's syndrome (CS), despite remission of hypercortisolism. The aim of this study was to evaluate prevalence of coronary artery disease in CS patients and its correlation with classical CV risk factors and inflammatory markers. Methods Cardiac multidetector computed tomography (MDCT) was performed in 41 patients (7 men, 31 of pituitary origin, 29 cured, mean age: 48.6 +/- 13 years), using 64-slice Toshiba Aquilion systems. Coronary atherosclerotic plaques were detected and coronary calcifications quantified by the Agatston score (AS). Clinical and biochemical parameters were correlated with the AS to identify possible surrogate markers of coronary disease. Normal values for clinical and biochemical parameters were obtained from a gender-and age-matched normal reference population (n = 82). Results CS patients with calcifications (AS>0) (N = 13, 32 %) had higher levels of sTNF-R1, homocysteine, triglycerides, blood pressure and body mass index than patients without calcifications (AS = 0) and those of normal reference population. Both groups of CS patients (AS>0 and AS = 0) had elevated trunk fat mass and IL-6 compared to reference values. Patients with AS>0 had less adiponectin and higher insulin, HOMA and fibrinogen than those found in normal reference population. sTNF-R1 correlated positively with AS and remained significant after adjusting for confounding factors. The same result was observed when we considered only cured CS patients. Conclusion In our cohort of CS patients sTNF-R1 was a predictor of coronary calcifications. Since MDCT is an expensive technique not readily available in daily clinical practice, increased sTNF-R1 could be a marker of CV risk even in cured CS.

Obesity elicits immune cell infiltration of adipose tissue provoking chronic low-grade inflammation. Regulatory T cells (Tregs) are specifically reduced in adipose tissue of obese animals. Since interleukin (IL)-21 plays an important role in inducing and maintaining immune-mediated chronic inflammatory processes and negatively regulates Treg differentiation/activity, we hypothesized that it could play a role in obesity-induced insulin resistance. We found IL-21 and IL-21R mRNA expression upregulated in adipose tissue of high-fat diet (HFD) wild-type (WT) mice and in stromal vascular fraction from human obese subjects in parallel to macrophage and inflammatory markers. Interestingly, a larger infiltration of Treg cells was seen in the adipose tissue of IL-21 knockout (KO) mice compared with WT animals fed both normal diet and HFD. In a context of diet-induced obesity, IL-21 KO mice, compared with WT animals, exhibited lower body weight, improved insulin sensitivity, and decreased adipose and hepatic inflammation. This metabolic phenotype is accompanied by a higher induction of interferon regulatory factor 4 (IRF4), a transcriptional regulator of fasting lipolysis in adipose tissue. Our data suggest that IL-21 exerts negative regulation on IRF4 and Treg activity, developing and maintaining adipose tissue inflammation in the obesity state.

Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers). (C) 2009 Elsevier B.V. All rights reserved.

Objective: To elucidate whether the risk of macrosomia, large for gestational age (LGA) and small for gestational age (SGA) is influenced by maternal body mass index and glucose tolerance differently in male and female fetuses. Methods: A population study was conducted in 16 general hospitals from the Spanish National Health Service that included 9270 consecutive women with singleton pregnancies and without a former diagnosis of diabetes mellitus who delivered 4793 male and 4477 female newborns. Logistic regression analyses were performed to predict the effect of body mass index (BMI) category and glucose tolerance on macrosomia, large for gestational age newborns (LGA) and small for gestational age newborns (SGA) Separate analyses according to foetal sex were carried out for each outcome. The results were adjusted for maternal age, gestational age and pregnancy-induced hypertension. Results: There were significant differences between males and females in the percentage of infants who had macrosomia, LGA or SGA. Maternal BMI category was positively associated with the risk of macrosomia and LGA in both male and female newborns. In addition, there was a negative association between maternal BMI and SGA that only reached significance in males. In contrast, gestational diabetes was only a predictor of macrosomia exclusively in male fetuses (OR 1.67, 95% CI 1.12 to 2.49) Conclusions: There is sexual dimorphism in the risk of abnormal birth weight attributed to maternal glucose tolerance status. A closer surveillance of foetal growth might be warranted in pregnant women with abnormal glucose tolerance carrying a male fetus.

Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers)., CIBEROBN is an initiative of ISCIII and CEAS Foundation, Spain.