Mitochondrial respiration is decreased in visceral but not subcutaneous adipose tissue in obese individuals with fatty liver disease

Adipose tissue (commonly called body fat) can be found under the skin (subcutaneous) or around internal organs (visceral). Dysfunction of adipose tissue can cause insulin resistance and lead to excess delivery of fat to other organs such as the liver. Herein, we show that dysfunction specifically in visceral adipose tissue was associated with fatty liver disease

UP-REGULATION OF STRESS-INDUCED LIGANDS IS ASSOCIATED WITH ENHANCED HEPATOCYTE APOPTOSIS AND FIBROSIS IN PATIENTS WITH NASH

60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases -- OCT 30-NOV 03, 2009 -- Boston, MAWOS: 000270456001033…Amer Assoc Study Liver Di

Longitudinal evaluation of efficacy, safety and nutritional status during one-year treatment with the duodenal-jejunal bypass liner

Abstract Background: The endoscopic duodenal-jejunal bypass liner (DJBL) represents a novel temporary endoscopic approach for treatment of obesity-associated type 2 diabetes. Recent results from the German DJBL registry confirmed substantial positive metabolic effects of the DJBL in type 2 diabetes. However, the last Food and Drug Administration trial was stopped due to a high occurrence of hepatic abscesses (3.5%). Objectives: Here, we analyzed time courses of development of co-morbidities, nutritive changes, and occurrence of adverse events during the 1-year treatment phase with the DJBL in the German DJBL registry. Methods: Sixty-six patients from the registry were analyzed for efficacy, safety, and nutritional status. Patient data sets were analyzed at implantation, 3 and 6 months after implantation, and at explantation visits. Results: Weight, body mass index, glycated hemoglobin, and low-density lipoprotein cholesterol primarily declined during the first 3 months after implantation, whereas systolic and diastolic blood pressure were predominantly reduced during the second half of the treatment phase. Severe DJBL-associated side effects were mainly documented at the explantation visit (intestinal obstruction [1.7%], dislocation [1.7%], and liver abscess [1.7%]). Measurements of serum concentrations of ferritin, albumin, vitamin B12, folic acid, 25-hydroxyvitamin D3 (25 OH-Vit-D3), and calcium provided suggestive evidence of a possible decrease of nutritional absorption of vitamins and trace elements by the DJBL. Conclusions: The DJBL demonstrates high efficacy with substantial improvement of all parameters of the metabolic syndrome and the potential for reduction of comedications in overweight patients with type 2 diabetes. These registry results are important to optimize recommendations for adaptation of concomitant medication, surveillance of adverse events, nutritional status and supplementation, and adaptation of the implantation period of the DJBL. [Epub 2018 Mar 9

Trends in BMI, Glycemic Control and Obesity-Associated Comorbidities After Explantation of the Duodenal-Jejunal Bypass Liner (DJBL)

Background A novel-approach for treatment of obesity and diabetes mellitus type 2 (T2DM) is represented by the endoscopic duodenal-jejunal bypass liner (DJBL). Recent data from the German DJBL registry provide evidence for substantial efficacy of the DJBL during the implantation period in obese patients with T2DM. However, little is known about the trends of glycemic control, BMI, and comorbidities after explantation of the DJBL, which have been investigated in the registry in this report. Methods Patients were selected from the registry if they had a dataset at implantation, explantation, and at least one time point after explantation of the DJBL (n =?77). We also investigated a subgroup of patients with available data at least 1 year (–2 weeks) after explantation of the DJBL (n =?32). Results For a mean BMI at implantation and a mean follow-up period, an increase of BMI of 2.1 kg/m2 (CI 0.8–3.2; p =?0.013) had to be expected (for HbA1c 0.3% (CI ??0.0–0.7; p =?n.s.), respectively). In the subgroup analysis, HbA1c and BMI increased after explantation of the DJBL but stayed significantly below baseline levels. Meanwhile, the mean number of antidiabetic drugs slightly increased. There was deterioration seen for blood pressure and LDL cholesterol over the postexplantation period to approximately baseline levels (or higher). Conclusion With this data, we show that improvement of HbA1c and BMI can be partly maintained over a time of nearly 1-year postexplantation of the DJBL. However, for HbA1c, this may be biased by intensified medical treatment and effects deteriorated with time after explantation. These results suggest that implantation of the DJBL needs to be integrated in a long-term weight management program as most of other interventions in obese patients with T2DM

Adaptation of Hepatic Mitochondrial Function in Humans with Non-Alcoholic Fatty Liver Is Lost in Steatohepatitis

SummaryThe association of hepatic mitochondrial function with insulin resistance and non-alcoholic fatty liver (NAFL) or steatohepatitis (NASH) remains unclear. This study applied high-resolution respirometry to directly quantify mitochondrial respiration in liver biopsies of obese insulin-resistant humans without (n = 18) or with (n = 16) histologically proven NAFL or with NASH (n = 7) compared to lean individuals (n = 12). Despite similar mitochondrial content, obese humans with or without NAFL had 4.3- to 5.0-fold higher maximal respiration rates in isolated mitochondria than lean persons. NASH patients featured higher mitochondrial mass, but 31%–40% lower maximal respiration, which associated with greater hepatic insulin resistance, mitochondrial uncoupling, and leaking activity. In NASH, augmented hepatic oxidative stress (H2O2, lipid peroxides) and oxidative DNA damage (8-OH-deoxyguanosine) was paralleled by reduced anti-oxidant defense capacity and increased inflammatory response. These data suggest adaptation of the liver (“hepatic mitochondrial flexibility”) at early stages of obesity-related insulin resistance, which is subsequently lost in NASH

Role of ECLS in Managing Post-Myocardial Infarction Ventricular Septal Rupture

Objectives: The aim of this study was to analyze outcomes in patients undergoing surgery for ventricular septal rupture (VSR) after myocardial infarction (MI) and the preoperative use of extracorporeal life support (ECLS) as a bridge to surgery. Methods: We included patients undergoing surgery for VSR from January 2009 until June 2021 from two centers in Germany. Patients were separated into two groups, those with and without ECLS, before surgery. Pre- and intraoperative data, outcome, and survival during follow-up were evaluated. Results: A total of 47 consecutive patients were included. Twenty-five patients were in the ECLS group, and 22 were in the group without ECLS. All the ECLS-group patients were in cardiogenic shock preoperatively. Most patients in the ECLS group were transferred from another hospital [n = 21 (84%) vs. no-ECLS (n = 12 (57.1%), p = 0.05]. We observed a higher number of postoperative bleeding complications favoring the group without ECLS [n = 6 (28.6%) vs. n = 16 (64%), p p = 1.0. Total in-hospital mortality was 38.3%. There was no significant difference in in-hospital mortality [n = 6 (27.3%) vs. n = 12 (48%), p = 0.11] and survival at last follow-up between the groups (p = 0.50). Conclusion: We detected no statistical difference in the in-hospital and long-term mortality in patients who received ECLS as supportive therapy after MI-induced VSR compared to those without ECLS. ECLS could be an effective procedure applied as a bridge to surgery in patients with VSR and cardiogenic shock