Diet change affects intestinal microbiota restoration and improves vertical sleeve gastrectomy outcome in diet-induced obese rats

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

Rapid perioperative changes in the quantitative properties of plasma lipases and lipoproteins in morbidly obese surgical patients'

Background: The impact of bariatric surgery on abnormalities in blood lipids and lipoprotein metabolism during the perioperative period has been poorly studied. Objective: We studied the impact of bariatric surgery on the composition and quantitative properties of lipoproteins and the activity of lipases in the plasma of perioperative morbidly obese patients. Methods: We examined the plasma lipoproteins and lipolytic activities of 34 morbidly obesepatients one month before surgery (OB), pre-anaesthesia (-S), post-anaesthesia ( S), and one day and one month after open Roux-en-Y gastric bypass (RYGB) surgery. Results: Surgical injury induced acute stress, as evidenced by transitory hyperglycaemia and elevated plasma levels of stress hormones. Lipid profiles revealed a significant reduction during surgery and the day after in the plasma levels of total cholesterol (p < 0.0001), which was mainly due to a decrease in low-density lipoprotein cholesterol (cLDL) and was confirmed with a significant reduction in the plasma levels of LDL (approximately 26% reduction). Significant (p < 0.0001) changes were detected in the plasma levels of high-density lipoprotein cholesterol (cHDL) as well as a significant decrease (approximately 19% reduction) in the plasma levels of HDL. A significant (p < 0.0001) rise was noted in the plasma levels of both Lipoprotein Lipase (LPL) (approximately 2.6-fold increase) and hepatic lipase (HL) (approximately 2.2-fold increase) on the day after surgery, occurring simultaneously with the maximum increase in C-reactive protein (CRP) and a day after the peak values for non-esterified fatty acid (NEFA), adrenocorticotropin hormone (ACTH), cortisol and glucose. Conclusion: The present study reveals unreported quantitative perioperative changes in plasma lipases and lipoproteins and related metabolic determinants that may contribute to the adaptive metabolic response to RYGB-induced stress

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.This research has received funding from the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III of the Spanish Ministry for Health and Consumer Affairs (PI030024, PI030042, PI070079 and PI11/01159

Diabetes Is the Main Factor Accounting for Hypomagnesemia in Obese Subjects

OBJECTIVE: Type 2 diabetes (T2DM) and obesity are associated with magnesium deficiency. We aimed to determine whether the presence of type 2 diabetes and the degree of metabolic control are related to low serum magnesium levels in obese individuals. METHODS: A) Case-control study: 200 obese subjects [50 with T2DM (cases) and 150 without diabetes (controls)] prospectively recruited. B) Interventional study: the effect of bariatric surgery on serum magnesium levels was examined in a subset of 120 obese subjects (40 with type 2 diabetes and 80 without diabetes). RESULTS: Type 2 diabetic patients showed lower serum magnesium levels [0.75±0.07 vs. 0.81±0.06 mmol/L; mean difference -0.06 (95% CI -0.09 to -0.04); p<0.001] than non-diabetic patients. Forty-eight percent of diabetic subjects, but only 15% of non-diabetic subjects showed a serum magnesium concentration lower than 0.75 mmol/L. Significant negative correlations between magnesium and fasting plasma glucose, HbA1c, HOMA-IR, and BMI were detected. Multiple linear regression analysis showed that fasting plasma glucose and HbA1c independently predicted serum magnesium. After bariatric surgery serum magnesium increased only in those patients in whom diabetes was resolved, but remain unchanged in those who not, without difference in loss weight between groups. Changes in serum magnesium negatively correlated with changes in fasting plasma glucose and HbA1c. Absolute changes in HbA1c independently predicted magnesium changes in the multiple linear regression analysis. CONCLUSIONS: Our results provide evidence that the presence of diabetes and the degree of metabolic control are essential in accounting for the lower levels of magnesium that exist in obese subjects

Guia de pràctica clínica: abordatge del tractament del dolor neuropàtic

Dolor neuropàtic; Epidemiologia; Hospital; Atenció primàriaDolor neuropático; Epidemiología; Hospital; Atención primariaNeuropathic pain; Epidemiology; Hospital; Primary careLa Guia pretén estructurar i consensuar l'atenció dels malalts amb dolor neuropàtic dins del nostre territori. S'especifiquen intervencions preventives i terapèutiques, així com a quin nivell el malalts han de ser atesos en funció de la seva situació clínica i la seva complexitat, els fluxos i metodologia bàsica de derivacions. Es vol potenciar un abordatge transversal i integral del dolor neuropàtic, que abasta l'atenció primària i l'atenció especialitzada hospitalària, i promoure la continuïtat assistencial entre ambdós nivells assistencials, tenint en compte intervencions i criteris compartits, per tal de disminuir la variabilitat de la pràctica clínica i millorar la qualitat i seguretat del pacient

Rapid perioperative changes in the quantitative properties of plasma lipases and lipoproteins in morbidly obese surgical patients'

Background: The impact of bariatric surgery on abnormalities in blood lipids and lipoprotein metabolism during the perioperative period has been poorly studied. Objective: We studied the impact of bariatric surgery on the composition and quantitative properties of lipoproteins and the activity of lipases in the plasma of perioperative morbidly obese patients. Methods: We examined the plasma lipoproteins and lipolytic activities of 34 morbidly obesepatients one month before surgery (OB), pre-anaesthesia (-S), post-anaesthesia ( S), and one day and one month after open Roux-en-Y gastric bypass (RYGB) surgery. Results: Surgical injury induced acute stress, as evidenced by transitory hyperglycaemia and elevated plasma levels of stress hormones. Lipid profiles revealed a significant reduction during surgery and the day after in the plasma levels of total cholesterol (p < 0.0001), which was mainly due to a decrease in low-density lipoprotein cholesterol (cLDL) and was confirmed with a significant reduction in the plasma levels of LDL (approximately 26% reduction). Significant (p < 0.0001) changes were detected in the plasma levels of high-density lipoprotein cholesterol (cHDL) as well as a significant decrease (approximately 19% reduction) in the plasma levels of HDL. A significant (p < 0.0001) rise was noted in the plasma levels of both Lipoprotein Lipase (LPL) (approximately 2.6-fold increase) and hepatic lipase (HL) (approximately 2.2-fold increase) on the day after surgery, occurring simultaneously with the maximum increase in C-reactive protein (CRP) and a day after the peak values for non-esterified fatty acid (NEFA), adrenocorticotropin hormone (ACTH), cortisol and glucose. Conclusion: The present study reveals unreported quantitative perioperative changes in plasma lipases and lipoproteins and related metabolic determinants that may contribute to the adaptive metabolic response to RYGB-induced stress

Linear correlations of fasting plasma glucose and HbA1c with serum magnesium in the whole population from the cross sectional case-control study.

<p>White circles, non-diabetic patients (fasting plasma glucose: r = −0.155, p = 0.059; HbA1c: r = −0.302, p = 0.002); black circles, type 2 diabetic patients (fasting plasma glucose: r = −0.484, p<0.001; HbA1c: r = −0.389, p = 0.010).</p

Three and 6-months evolution after RYGBP of serum magnesium concentrations in non-diabetic subjects, and both type 2 diabetic obese patients who resolve and not resolve their diabetes.

<p>No differences in EBWL (excess body weight loss) was observed between type 2 diabetic subjects who resolved and not resolved their diabetes at 3-months (38.39±8.10 <i>vs.</i> 35.38±14.69%, p = 0.480), nor 6-months (50.87±12.05 <i>vs.</i> 48.77±17.27%; p = 0.687) of follow up.</p

Hepatic CD36 downregulation parallels steatosis improvement in morbidly obese undergoing bariatric surgery

[Background] The notion that hepatic expression of genes involved in lipid metabolism is altered in obese patients is relatively new and its relationship with hepatic steatosis and cardiometabolic alterations remains unclear. [Objective] We assessed the impact of Roux-en-Y gastric bypass surgery (RYGB) on the expression profile of genes related to metabolic syndrome in liver biopsies from morbidly obese individuals using a custom-made, focused cDNA microarray, and assessed the relationship between the expression profile and hepatic steatosis regression. [Materials and methods] Plasma and liver samples were obtained from patients at baseline and 12 months after surgery. Samples were assayed for chemical and gene expression analyses, as appropriate. Gene expression profiles were assessed using custom-made, focused TaqMan low-density array cards. [Results] RYGB-induced weight loss produced a favorable reduction in fat deposits, insulin resistance (estimated by homeostasis model assessment of insulin resistance (HOMA-IR)), and plasma and hepatic lipid levels. Compared with the baseline values, the gene expression levels of key targets of lipid metabolism were significantly altered: CD36 was significantly downregulated (−40%; P=0.001), whereas APOB (+27%; P=0.032) and SCARB1 (+37%; P=0.040) were upregulated in response to surgery-induced weight reduction. We also observed a favorable reduction in the expression of the PAI1 gene (−80%; P=0.007) and a significant increase in the expression of the PPARA (+60%; P=0.014) and PPARGC1 genes (+36%; P=0.015). Notably, the relative fold decrease in the expression of the CD36 gene was directly associated with a concomitant reduction in the cholesterol (Spearman’s r=0.92; P=0.001) and phospholipid (Spearman’s r=0.76; P=0.04) contents in this tissue. [Conclusions] For the first time, RYGB-induced weight loss was shown to promote a favorable downregulation of CD36 expression, which was proportional to a favorable reduction in the hepatic cholesterol and phospholipid contents in our morbidly obese subjects following surgery.This work was funded by the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (ISCIII) FIS grants CP13/00070 (to JJ) and PI11/01159 and PI15/00190 (to JP-O), and FEDER ‘Una manera de hacer Europa’; and by LaMarató 2016 (303/C/2016) (to JJ). JJ is recipient of a Miguel Servet Type 1 contract (CP13/00070; ISCIII). KAM-L is recipient of a AGAUR grant FI-DGR2014 (Generalitat de Catalunya). CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) is a project of the Instituto de Salud Carlos III. Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau is accredited by the Generalitat de Catalunya as Centre de Recerca de Catalunya (CERCA).Peer reviewe