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

Retrieval of the gastric specimen following laparoscopic sleeve gastrectomy. Experience on 275 cases.

Severe obesity leads to a high incidence of complications and a decrease in life expectancy, especially among younger adults. Laparoscopic sleeve gastrectomy (LSG) first intended as the first step of biliopancreatic diversion with duodenal switch is gaining a per-se procedure role because of its effectiveness on weight loss and comorbidity resolution. Different techniques have been described for specimen extraction in LSG. In this article we report the technique adopted in 275 LSGs performed in our department. In the first 120 LSGs performed from 2007, the specimen was extracted through a mini laparotomy. In the following 155 cases the technique has been simplified: the grasped specimen has been withdrawn through the 15 mm trocar site. We registered in the fist group six cases of wound infection (5%), ten cases of hematoma (8.3%) and four cases of port site hernia (3.3%). In the second group only one case of hematoma (0.6%, p = 0.01) but no cases of wound infection (p = 0.01) or port site hernia, (p = 0.03) although we registered a specimen perforation during retrieval in 16 patients, were reported. The technique described in the 155 cases of the control group has shown to be more effective than the technique we used in the case group, allowing significantly lower operative time (112.9 ± 1.0 vs 74.9 ± 9.1 p < 0.001) and complications, and providing unchanged costs

Cardiac Hypertrophy: from Pathophysiological Mechanisms to Heart Failure Development

Cardiac hypertrophy develops in response to increased workload to reduce ventricular wall stress and maintain function and efficiency. Pathological hypertrophy can be adaptive at the beginning. However, if the stimulus persists, it may progress to ventricular chamber dilatation, contractile dysfunction, and heart failure, resulting in poorer outcome and increased social burden. The main pathophysiological mechanisms of pathological hypertrophy are cell death, fibrosis, mitochondrial dysfunction, dysregulation of Ca2+-handling proteins, metabolic changes, fetal gene expression reactivation, impaired protein and mitochondrial quality control, altered sarcomere structure, and inadequate angiogenesis. Diabetic cardiomyopathy is a condition in which cardiac pathological hypertrophy mainly develop due to insulin resistance and subsequent hyperglycaemia, associated with altered fatty acid metabolism, altered calcium homeostasis and inflammation. In this review, we summarize the underlying molecular mechanisms of pathological hypertrophy development and progression, which can be applied in the development of future novel therapeutic strategies in both reversal and prevention