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

Predictive value of the advanced lipoprotein profile and glycated proteins on diabetic retinopathy

This study aimed to assess whether the advanced characteristics of serum lipoprotein subclasses could better predict the risk of developing diabetic retinopathy (DR) and its severity compared to other established risk factors in subjects with type 1 (T1D) and type 2 (T2D) diabetes. This observational, cross-sectional substudy analyzed DR-related data from 309 T1D and 264 T2D subjects. The advanced lipoprotein and glycoprotein profile was determined by nuclear magnetic resonance (NMR) spectroscopy (Liposcale test). NMR analysis of lipoproteins revealed that T1D subjects with DR showed standard non-HDL particles, despite higher IDL lipid concentrations. Notably, IDL lipids were elevated in T1D subjects with worsened DR. VLDL and LDL were smaller, whereas HDL triglycerides were increased in DR compared with non-DR. On the other hand, the T2D subjects with DR showed altered characteristics in the LDL fraction, mainly revealed by a significant decrease in smaller LDL and a reduction in LDL-C. Moreover, the glycoprotein profile did not reveal significant changes among DR groups, regardless of the type of diabetes. However, lipoprotein characteristics and glycoproteins unveiled by NMR analysis did not improve the predictive value of conventional lipids or other traditional, well-established biomarkers of DR in our cohorts

Predictive Value of the Advanced Lipoprotein Profile and Glycated Proteins on Diabetic Retinopathy

This study aimed to assess whether the advanced characteristics of serum lipoprotein subclasses could better predict the risk of developing diabetic retinopathy (DR) and its severity compared to other established risk factors in subjects with type 1 (T1D) and type 2 (T2D) diabetes. This observational, cross-sectional substudy analyzed DR-related data from 309 T1D and 264 T2D subjects. The advanced lipoprotein and glycoprotein profile was determined by nuclear magnetic resonance (NMR) spectroscopy (Liposcale test). NMR analysis of lipoproteins revealed that T1D subjects with DR showed standard non-HDL particles, despite higher IDL lipid concentrations. Notably, IDL lipids were elevated in T1D subjects with worsened DR. VLDL and LDL were smaller, whereas HDL triglycerides were increased in DR compared with non-DR. On the other hand, the T2D subjects with DR showed altered characteristics in the LDL fraction, mainly revealed by a significant decrease in smaller LDL and a reduction in LDL-C. Moreover, the glycoprotein profile did not reveal significant changes among DR groups, regardless of the type of diabetes. However, lipoprotein characteristics and glycoproteins unveiled by NMR analysis did not improve the predictive value of conventional lipids or other traditional, well-established biomarkers of DR in our cohorts.This work was funded by the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (Madrid, Spain), grant PI15/0625 (to D.M. and E.C.), PI17/01362 (to N.A.), and PI17/00232 (to J.J.), FEDER “Una manera de hacer Europa,” and by Fundació La Marató de TV3 2016 (303/C/2016) (201602.30.31) (to N.A. and J.J.). J.J. was a recipient of a Miguel Servet Type 2 contract (CPII18/00004; ISCIII). This research was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red-CIBERDEM (CB15/00071), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación. 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)

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

Bariatric surgery and diet change in rats

[eng] An unbalanced, unhealthy diet is one of the main causes leading to obesity and the apparition of comorbidities. Bariatric surgery is currently the most effective and durable treatment against obesity. Despite being a commonly performed technique is still much investigated, as the mechanisms by which the weight is reduced and the comorbidities are improved are still largely unknown. Implementing healthier dietary habits after BS appears to be decisive to maintain the obtained benefits, besides the mechanistic restriction of the BS. On the other hand, dieting alone is also described to have beneficial effects if well implemented. Based on this information, we established the following hypothesis: A high-fat diet will induce modifications on a rodent model, such as increasing adiposity, unbalancing the gut microbiota, and modifying the fatty acid composition of several organs. The deleterious effects produced by the high-fat diet will be partly improved by either vertical sleeve gastrectomy or by a change of diet, while the combination of both actions will have a synergistic effect and a better outcome than both actions alone. To explore this hypothesis the following objectives were formulated: • Identify the major modifications caused by the HFD on adiposity, gut microbiota composition, and fatty acid composition in tissues. • Study the effects caused by VSG when the high-fat diet is continued. • Study the effects caused by a change of diet alone. • Study the effects caused by a combination of VSG and a change of diet

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

Hepatic and Visceral Adipose Tissue 11bHSD1 Expressions are Markers of Body Weight Loss After Bariatric Surgery

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

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