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This study investigated the effect of nicotinamide (NAM) supplementation on the development of brain inflammation and microglial activation in a mouse model of type 1 diabetes mellitus. C57BL/6J male mice, which were made diabetic with five consecutive, low-dose (55 mg/kg i.p.) streptozotocin (STZ) injections. Diabetic mice were randomly distributed in different experimental groups and challenged to different doses of NAM (untreated, NAM low-dose, LD, 0.1%; NAM high-dose, HD, 0.25%) for 25 days. A control, non-diabetic group of mice was used as a reference. The NAD+ content was increased in the brains of NAM-treated mice compared with untreated diabetic mice (NAM LD: 3-fold; NAM HD: 3-fold, p-value < 0.05). Immunohistochemical staining revealed that markers of inflammation (TNFα: NAM LD: −35%; NAM HD: −46%; p-value < 0.05) and microglial activation (IBA-1: NAM LD: −29%; NAM HD: −50%; p-value < 0.05; BDKRB1: NAM LD: −36%; NAM HD: −37%; p-value < 0.05) in brains from NAM-treated diabetic mice were significantly decreased compared with non-treated T1D mice. This finding was accompanied by a concomitant alleviation of nuclear NFκB (p65) signaling in treated diabetic mice (NFκB (p65): NAM LD: −38%; NAM HD: −53%, p-value < 0.05). Notably, the acetylated form of the nuclear NFκB (p65) was significantly decreased in the brains of NAM-treated, diabetic mice (NAM LD: −48%; NAM HD: −63%, p-value < 0.05) and inversely correlated with NAD+ content (r = −0.50, p-value = 0.03), suggesting increased activity of NAD+-dependent deacetylases in the brains of treated mice. Thus, dietary NAM supplementation in diabetic T1D mice prevented brain inflammation via NAD+-dependent deacetylation mechanisms, suggesting an increased action of sirtuin signaling.

Purpose Obesity, a worldwide health problem, is linked to an abnormal gut microbiota and is currently most efectively treated by bariatric surgery. Our aim was to characterize the microbiota of high-fat fed Sprague–Dawley rats when subjected to bariatric surgery (i.e., vertical sleeve gastrectomy) and posterior refeeding with either a high-fat or control diet. We hypothesized that bariatric surgery followed by the control diet was more efective in reverting the microbiota modifcations caused by the high-fat diet when compared to either of the two factors alone. Methods Using next-generation sequencing of ribosomal RNA amplicons, we analyzed and compared the composition of the cecal microbiota after vertical sleeve gastrectomy with control groups representing non-operated rats, control fed, high-fat fed, and post-operative diet-switched animals. Rats were fed either a high-fat or control low-fat diet and were separated into three comparison groups after eight weeks comprising no surgery, sham surgery, and vertical sleeve gastrectomy. Half of the rats were then moved from the HFD to the control diet. Using next-generation sequencing of ribosomal RNA amplicons, we analyzed the composition of the cecal microbiota of rats allocated to the vertical sleeve gastrectomy group and compared it to that of the non-surgical, control fed, high-fat fed, and post-operative diet-switched groups. Additionally, we correlated diferent biological parameters with the genera exhibiting the highest variation in abundance between the groups. Results The high-fat diet was the strongest driver of altered taxonomic composition, relative microbial abundance, and diversity in the cecum. These efects were partially reversed in the diet-switched cohort, especially when combined with sleeve gastrectomy, resulting in increased diversity and shifting relative abundances. Several highly-afected genera were correlated with obesity-related parameters. Conclusions The dysbiotic state caused by high-fat diet was improved by the change to the lower fat, higher fber control diet. Bariatric surgery contributed signifcantly and additively to the diet in restoring microbiome diversity and complexity. These results highlight the importance of dietary intervention following bariatric surgery for improved restoration of cecal diversity, as neither surgery nor change of diet alone had the same efects as when combined. This work was supported by the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (ISCIII) (PI11/01159, PI15/00190 and PI15/00332 to JAB-F and JP-O), was co-fnanced by European Union Funds, Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa”. Additional funding from the Stockholm Health Authority grant # SLL 20160933 was awarded to KIU

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. 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. The DIO group had higher and significant weight gain than the C group at the time of surgery (p

Cortisolemia and 11βHSD1 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.

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.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.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 p0.0001, respectively) and in anaemia parameters (e.g., folate, cobalamin and transferrin, p = 0.0002, p0.0001 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.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.

Although intermediate metabolism is known to follow circadian rhythms, little information is available on the variation in lipase activities (lipoprotein and hepatic lipase, LPL and HL, respectively) and lipids throughout the year. In a cross-sectional study, we collected and analysed blood from 245 healthy students (110 men and 135 women) between 18 and 25 years old from the University of Barcelona throughout the annual campaign (March, May, October and December) of the blood bank. All subjects gave their written informed consent to participate. All blood samples were taken after breakfast at 8:00 and 11:00 am. Plasma glucose, total plasma protein, triacylglycerides (TAG), free fatty acids (FFA), free cholesterol and esterified cholesterol (FC and TC, respectively), cholesterol in low-density lipoproteins (cLDL), cholesterol in high-density lipoproteins (cHDL), phospholipids (PL) and lipase activities (LPL and HL) were determined. Cosinor analysis was used to evaluate the presence (significance of fit cosine curve to data and variance explained by rhythm) and characteristics of possible 12-month rhythms (acrophase, MESOR and amplitude). Statistically significant seasonal rhythms were detected for all the variables studied except proteins, with most of them peaking in the winter season. The lowest value for cLDL and the HL occurs in summer, while for cHDL and the LPL it is in winter. These findings demonstrate for the first time that in physiological conditions, plasma LPL and HL activities and lipids follow seasonal rhythms. The metabolic significance of this pattern is discussed.

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

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 tri-glycerides, 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 anti-atherogenic 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 (similar to-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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Cortisolemia and 11βHSD1 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.A group of 34 patients with morbid obesity and 22 nonobese subjects were recruited. Initial hypothalamus-pituitary-adrenal (HPA) basal activity and 11βHSD1 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.Body weight loss was accompanied by a downshift in basal HPA activity and 11βHSD1 expression in SAT. In patients with morbid obesity, 11βHSD1 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 11βHSD1 expression in SAT.Body weight loss after bariatric surgery is accompanied by a downshift in basal HPA activity. Hepatic and VAT 11βHSD1 expressions in morbid obesity are predictors of body weight loss.

We have investigated the differences between metabolically "healthy" morbidly obese patients and those with comorbidities.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.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.The morbidly obese "healthy" individual is not really metabolically healthy, but morbidly obese individuals with diabetes and dyslipidemia are more metabolically imbalanced.

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