Clinical epigenetics and restoring of metabolic health in severely obese patients undergoing batriatric and metabolic surgery

Epigenetic-sensitive mechanisms, mainly DNA methylation, mirror the relationship between environmental and genetic risk factors able to affect the sensitiveness to development of obesity and its comorbidities. Bariatric and metabolic surgery may reduce obesity-related cardiovascular risk through tissue-specific DNA methylation changes. Among the most robust results, differential promoter methylation of ACACA, CETP, CTGF, S100A8, and S100A9 genes correlated significantly with the levels of mRNA before and after gastric bypass surgery (RYGB) in obese women. Additionally, promoter hypermethylation of NFKB1 gene was significantly associated with reduced blood pressure in obese patients after RYGB suggesting useful non-invasive biomarkers. Of note, sperm-related DNA methylation signatures of genes regulating the central control of appetite, such as MC4R, BDNF, NPY, and CR1, and other genes including FTO, CHST8, and SH2B1 were different in obese patients as compared to non-obese subjects and patients who lost weight after RYGB surgery. Importantly, transgenerational studies provided relevant evidence of the potential effect of bariatric and metabolic surgery on DNA methylation. For example, peripheral blood biospecimens isolated from siblings born from obese mothers before bariatric surgery showed different methylation signatures in the insulin receptor and leptin signaling axis as compared to siblings born from post-obese mothers who underwent surgery. This evidence suggests that bariatric and metabolic surgery of mothers may affect the epigenetic profiles of the offspring with potential implication for primary prevention of severe obesity. We update on tissue-specific epigenetic signatures as potential mechanisms underlying the restoration of metabolic health after surgery suggesting useful predictive biomarkers

Bariatric Surgery Reduces Oxidative Stress by Blunting 24-h Acute Glucose Fluctuations in Type 2 Diabetic Obese Patients

OBJECTIVE - We evaluated the efficacy of malabsorptive bariatric surgery on daily blood glucose fluctuations and oxidative stress in type 2 diabetic obese patients. RESEARCH DESIGN AND METHODS - The 48-h continuous subcutaneous glucose monitoring was assessed in type 2 diabetic patients before and 1 month after biliopancreatic diversion (BPD) (n = 36), or after diet-induced equivalent weight loss (n = 20). The mean amplitude of glycemic excursions and oxidative stress (nitrotyrosine) were evaluated during continuous subcutaneous glucose monitoring. During a standardized meal, glucagon-like peptide (GLP)-1, glucagon, and insulin were measured. RESULTS - Fasting and postprandial glucose decreased equally in surgical and diet groups. A marked increase in GLP-1 occurred during the interprandial period in surgical patients toward the diet group (P < 0.01). Glucagon was more suppressed during the interprandial period in surgical patients compared with the diet group (P < 0.01). Mean amplitude of glycemic excursions and nitrotyrosine levels decreased more after BPD than after diet (P < 0.01). CONCLUSIONS - Oxidative stress reduction after biliopancreatic diversion seems to be related to the regulation of glucose fluctuations resulting from intestinal bypass. © 2010 by the American Diabetes Association

A modified Rives–Stoppa technique with composite mesh (FLaPp) in large incisional hernia: a multicentric retrospective cohort study

Background Large incisional hernias (LIH) are challenging conditions, often necessitating complex surgical procedures such as transversus abdominis muscle release (TAR). We evaluated the feasibility and effectiveness of tension-free abdominal wall repair of LIH with an innovative modified Rives–Stoppa procedure employing a composite free lateral polypropylene (FLaPp) prosthesis. Methods Symptomatic patients affected by LIH and treated with FLaPp composite prosthesis between April 2010 and December 2016 were retrospectively analyzed. The FLaPp prosthesis is made up of two layers: an internal layer based on a polypropylene film that can be used in contact with the intestinal loops to address the posterior peritoneal defect, and an external layer based on a macroporous lightweight mesh, with which a classic repair according to Rives–Stoppa is carried out. Results Forty-three patients were enrolled in the study. All hernias were W3. Early complications were seroma (16.3%), hematoma (11.6%), wound infection (7.0%), and bowel injury (2.3%). Late complications were sinus tract (4.7%), occasional pain (2.3%), and stiff abdomen (9.3%). The median operative time was 126 min and median hospitalization was 8 days. At the median follow-up of 40 months (range 37.5–117), the recurrence rate was 9.3% (4/43). Conclusion Use of FLaPp mesh with a tension-free surgical approach is an effective strategy for managing LIH in selected cases with the presence of a posterior defect, with low rates of complications and recurrences

CXCL4 in undifferentiated connective tissue disease at risk for systemic sclerosis (SSc) (previously referred to as very early SSc)

The aim of the study was to evaluate CXCL4 levels in undifferentiated connective tissue disease at risk for SSc (UCTD-SSc-risk) and confirm its increase and investigate its prognostic value. Serum CXCL4 levels were measured in 45 patients and 24 controls. CXCL4 was significantly higher in UCTD-SSc-risk patients than in controls. It resulted higher in patients with a shorter disease duration and in those lacking capillaroscopic alterations. We confirm that CXCL4 levels are increased in UCTD-risk-SSc patients. Further studies are needed to investigate the role of CXCL4 assessment in UCTD-risk-SSc

Metabolomic fingerprinting of renal disease progression in Bardet-Biedl syndrome reveals mitochondrial dysfunction in kidney tubular cells.

Chronic kidney disease (CKD) is a major clinical sign of patients with Bardet-Biedl syndrome (BBS), especially in those carrying BBS10 mutations. Twenty-nine patients with BBS and 30 controls underwent a serum-targeted metabolomic analysis. In vitro studies were conducted in two kidney-derived epithelial cell lines, where Bbs10 was stably deleted (IMCD3-Bbs10-/-cells) and over-expressed. The CKD status affected plasmatic metabolite fingerprinting in both patients with BBS and controls. Specific phosphatidylcholine and acylcarnitines discriminated eGFR decline only in patients with BBS. IMCD3-Bbs10-/ cells displayed intracellular lipidaccumulation, reduced mitochondrial potential membrane and citrate synthase staining. Mass-Spectrometry-based analysis revealed that human BBS10 interacted with six mitochondrial proteins, in vitro. In conclusion, renal dysfunction correlated with abnormal phosphatidylcholine and acylcarnitines plasma levels in patients with BBS; in vitro, Bbs10 depletion caused mitochondrial defects while human BBS10 interacted with several mitochondria-related proteins, suggesting an unexplored role of this protein