High-protein diet more effectively reduces hepatic fat than low-protein diet despite lower autophagy and FGF21 levels.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent and nutrition intervention remains the most important therapeutic approach for NAFLD. Our aim was to investigate whether low- (LP) or high-protein (HP) diets are more effective in reducing liver fat and reversing NAFLD and which mechanisms are involved. METHODS: 19 participants with morbid obesity undergoing bariatric surgery were randomized into two hypocaloric (1500-1600 kcal/day) diet groups, a low protein (10E% protein) and a high protein (30E% protein), for three weeks prior to surgery. Intrahepatic lipid levels (IHL) and serum fibroblast growth factor 21 (FGF21) were measured before and after the dietary intervention. Autophagy flux, histology, mitochondrial activity and gene expression analyses were performed in liver samples collected during surgery. RESULTS: IHL levels decreased by 42.6% in the HP group, but were not significantly changed in the LP group despite similar weight loss. Hepatic autophagy flux and serum FGF21 increased by 66.7% and 42.2%, respectively, after 3 weeks in the LP group only. Expression levels of fat uptake and lipid biosynthesis genes were lower in the HP group compared with those in the LP group. RNA-seq analysis revealed lower activity of inflammatory pathways upon HP diet. Hepatic mitochondrial activity and expression of ß-oxidation genes did not increase in the HP group. CONCLUSIONS: HP diet more effectively reduces hepatic fat than LP diet despite of lower autophagy and FGF21. Our data suggest that liver fat reduction upon HP diets result primarily from suppression of fat uptake and lipid biosynthesis.

The novel adipokine WISP1 associates with insulin resistance and impairs insulin action in human myotubes and mouse hepatocytes.

AIMS/HYPOTHESIS: Wingless-type (Wnt) inducible signalling pathway protein-1 (WISP1) has been recently identified as a proinflammatory adipokine. We examined whether WISP1 expression and circulating levels are altered in type 2 diabetes and whether WISP1 affects insulin signalling in muscle cells and hepatocytes. METHODS: Serum and visceral adipose tissue (VAT) biopsies, for analysis of circulating WISP1 levels by ELISA and WISP1 mRNA expression by real-time quantitative RT-PCR, were collected from normal-weight men (control group, n = 33) and obese men with (n = 46) and without type 2 diabetes (n = 56) undergoing surgery. Following incubation of primary human skeletal muscle cells (hSkMCs) and murine AML12 hepatocytes with WISP1 and insulin, insulin signalling was analysed by western blotting. The effect of WISP1 on insulin-stimulated glycogen synthesis and gluconeogenesis was investigated in hSkMCs and murine hepatocytes, respectively. RESULTS: Circulating WISP1 levels were higher in obese men (independent of diabetes status) than in normal-weight men (mean [95% CI]: 70.8 [55.2, 86.4] ng/l vs 42.6 [28.5, 56.6] ng/l, respectively; p < 0.05). VAT WISP1 expression was 1.9-fold higher in obese men vs normal-weight men (p < 0.05). Circulating WISP1 levels were positively associated with blood glucose in the OGTT and circulating haem oxygenase-1 and negatively associated with adiponectin levels. In hSkMCs and AML12 hepatocytes, recombinant WISP1 impaired insulin action by inhibiting phosphorylation of insulin receptor, Akt and its substrates glycogen synthase kinase 3ß, FOXO1 and p70S6 kinase, and inhibiting insulin-stimulated glycogen synthesis and suppression of gluconeogenic genes. CONCLUSIONS/INTERPRETATION: Circulating WISP1 levels and WISP1 expression in VAT are increased in obesity independent of glycaemic status. Furthermore, WISP1 impaired insulin signalling in muscle and liver cells.

A 30 mm sized gastrojejunostomy may lead to a lower rate of therapy failure in comparison to a 45 mm sized gastrojejunostomy following laparoscopic Roux-en-Y gastric bypass.

Background: In bariatric surgery the laparoscopic Roux-en-Y gastric bypass (LRYGB) has been proven to be a safe and effective approach. Currently the optimal size of the linear-stapled gastrojejunostomy (GJ) and its impact on weight loss are not known due to a lack of clinical trials on that topic. We aimed to provide evidence on the impact of the GJ size in terms of gastric bypass weight loss. Methods: Patients who underwent LRYGB due to morbid obesity were retrospectively analyzed from January 2013 to January 2016. While the procedure was completely standardized, one surgeon continued using the 45 mm sized linear stapler to perform GJ while the other switched to using a 30 mm cartridge. Results: 277 patients were female (78%) and 77 males. The average age was 41.7 ± 12.3 years. In 118 cases a 30 mm sized GJ was conducted. 236 individuals received a 45 mm sized GJ. In terms of gender, age, length of biliary and alimentary limb both groups were homogenous. Individuals with a 30 mm sized GJ had a statistical significant lower rate of therapy failure (Excess weight loss <25%, 25-49%, ≥50% after 3 years, P value χ2 for trend <0.035).The excess weight loss did not significant differ between both groups. Conclusions: A 30 mm sized GJ may lead to a lower rate of therapy failure in comparison to a 45 mm sized GJ following laparoscopic Roux-en-Y gastric bypass. Prospective trials are mandatory to confirm our findings.

Broadband Zero-Power Wakeup MEMS Device for Energy-Efficient Sensor Nodes.

A zero-power wakeup scheme for energy-efficient sensor applications is presented in this study based on a piezoelectric MEMS energy harvester featuring wafer-level-integrated micromagnets. The proposed setup overcomes a hybrid assembly of magnets on a chip-level, a major drawback of similar existing solutions. The wakeup device can be excited at low frequencies by frequency up-conversion, both in mechanical contact and contactless methods due to magnetic force coupling, allowing various application scenarios. In a discrete circuit, a wakeup within 30−50 ms is realized in frequency up-conversion at excitation frequencies < 50 Hz. A power loss in the off state of 0.1 nW renders the scheme virtually lossless. The potential extension of battery lifetime compared to cyclical wakeup schemes is discussed for a typical wireless sensor node configuration.

Hepatic Wnt1 Inducible Signaling Pathway Protein 1 (WISP-1/CCN4) Associates with Markers of Liver Fibrosis in Severe Obesity.

Liver fibrosis is a critical complication of obesity-induced fatty liver disease. Wnt1 inducible signaling pathway protein 1 (WISP1/CCN4), a novel adipokine associated with visceral obesity and insulin resistance, also contributes to lung and kidney fibrosis. The aim of the present study was to investigate the role of CCN4 in liver fibrosis in severe obesity. For this, human liver biopsies were collected from 35 severely obese humans (BMI 42.5 ± 0.7 kg/m2, age 46.7 ± 1.8 y, 25.7% males) during bariatric surgery and examined for the expression of CCN4, fibrosis, and inflammation markers. Hepatic stellate LX-2 cells were treated with human recombinant CCN4 alone or in combination with LPS or transforming growth factor beta (TGF-ß) and examined for fibrosis and inflammation markers. CCN4 mRNA expression in the liver positively correlated with BMI and expression of fibrosis markers COL1A1, COL3A1, COL6A1, αSMA, TGFB1, extracellular matrix turnover enzymes TIMP1 and MMP9, and the inflammatory marker ITGAX/CD11c. In LX-2 cells, the exposure to recombinant CCN4 caused dose-dependent induction of MMP9 and MCP1. CCN4 potentiated the TGF-ß-mediated induction of COL3A1, TIMP1, and MCP1 but showed no interaction with LPS treatment. Our results suggest a potential contribution of CCN4 to the early pathogenesis of obesity-associated liver fibrosis.

Banding the Pouch with a Non-adjustable Ring as Revisional Procedure in Patients with Insufficient Results After Roux-en-Y Gastric Bypass: Short-term Outcomes of a Multicenter Cohort Study.

BACKGROUND: After laparoscopic Roux-en-Y gastric bypass (RYGB), approximately 10-35% of patients with morbid obesity regain weight after an initial good result or fail to achieve a sufficient amount of weight loss. Patients in which conservative measures are not successful may potentially benefit from revisional surgery. OBJECTIVE: To evaluate the effect of a non-adjustable ring placed around the gastric pouch in patients with insufficient weight loss or weight regain after RYGB. SETTING: Four specialized bariatric hospitals in The Netherlands, Germany, and Switzerland. METHODS: From 2011 to 2017, 79 patients underwent revisional surgery using a non-adjustable silicone ring because of insufficient results after RYGB. Data on weight loss and complications up to 2 years after revisional surgery was collected and analyzed retrospectively. RESULTS: A follow-up percentage of 86% after 1 year and 61% after 2 years was achieved. In 75% of patients, further weight regain was prevented. Percentage total body weight loss improved by 7 to 26% 1 year after revisional surgery and remained stable during 2 years of follow-up. The additional weight loss effect of placing a non-adjustable ring was more pronounced in patients with an initial good result after primary RYGB. Eighteen (23%) rings were removed, most often due to dysphagia. CONCLUSION: Especially for patients who experience weight regain after initial good weight loss, placing a non-adjustable silicone ring around the gastric pouch results in modest improvements in weight loss. To prevent the risk of ring removal due to dysphagia, surgeons should take notice not to place the ring too tight around the gastric pouch during revisional surgery.

Effects of High and Low Protein Diets on Inflammatory Profiles in People with Morbid Obesity: A 3-Week Intervention Study.

Nutritional interventions in morbidly obese individuals that effectively reverse a pro-inflammatory state and prevent obesity-associated medical complications are highly warranted. Our aim was to evaluate the effect of high (HP) or low (LP) protein diets on circulating immune-inflammatory biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), chemerin, omentin, leptin, total adiponectin, high molecular weight adiponectin, and fetuin-A. With this aim, 18 people with morbid obesity were matched into two hypocaloric groups: HP (30E% protein, n = 8) and LP (10E% protein, n = 10) for three weeks. Biomarkers were measured pre and post intervention and linear mixed-effects models were used to investigate differences. Consuming HP or LP diets resulted in reduced CRP (HP: -2.2 ± 1.0 mg/L, LP: -2.3 ± 0.9 mg/L) and chemerin (HP: -17.9 ± 8.6 ng/mL, LP: -20.0 ± 7.4 ng/mL), with no statistically significant differences by diet arm. Participants following the LP diet showed a more pronounced decrease in leptin (-19.2 ± 6.0 ng/mL) and IL-6 (-0.4 ± 0.1 pg/mL) and an increase in total adiponectin (1.6 ± 0.6 µg/mL). Changes were also observed for the remaining biomarkers to a smaller degree by the HP than the LP hypocaloric diet, suggesting that a LP hypocaloric diet modulates a wider range of immune inflammatory biomarkers in morbidly obese individuals.

Simulation-Based Training - Evaluation of the Course Concept "Laparoscopic Surgery Curriculum" by the Participants.

INTRODUCTION: The learning curve in minimally invasive surgery is much longer than in open surgery. This is thought to be due to the higher demands made on the surgeon's skills. Therefore, the question raised at the outset of training in laparoscopic surgery is how such skills can be acquired by undergoing training outside the bounds of clinical activities to try to shorten the learning curve. Simulation-based training courses are one such model. METHODS: In 2011, the surgery societies of Germany adopted the "laparoscopic surgery curriculum" as a recommendation for the learning content of systematic training courses for laparoscopic surgery. The curricular structure provides for four 2-day training courses. These courses offer an interrelated content, with each course focusing additionally on specific topics of laparoscopic surgery based on live operations, lectures, and exercises carried out on bio simulators. RESULTS: Between 1st January, 2012 and 31st March, 2016, a total of 36 training courses were conducted at the Vivantes Endoscopic Training Center in accordance with the "laparoscopic surgery curriculum." The training courses were attended by a total of 741 young surgeons and were evaluated as good to very good during continuous evaluation by the participants. CONCLUSION: Training courses based on the "laparoscopic surgery curriculum" for acquiring skills in laparoscopy are taken up and positively evaluated by young surgeons.

Status of bariatric surgery in Germany--results of the nationwide survey on bariatric surgery 2005-2007.

BACKGROUND: Most studies on bariatric surgery outcomes are performed as clinical trials or reflect the clinical experience in single centers. The status of bariatric surgery in Germany has been examined with the cooperation of clinics and hospitals at the Institute of Quality Assurance in Surgery at the Ottovon-Guericke University of Magdeburg (Germany) since January 1, 2005. METHODS: In this prospective multicenter observational study, the data obtained for all primary bariatric procedures, including all repeated operations, performed on consecutive patients with morbid obesity at participating hospitals from 2005 to 2007 were prospectively collected using an internet online data registry. Perioperative characteristics such as the spectrum of diagnostic measurements, type of surgical procedures, and short- and long-term outcomes were investigated. RESULTS: During the study period 3,123 surgical procedures were performed. In 2005 and 2006, gastric banding (GB) was the operation performed most frequently, followed by the Roux-en-Y gastric bypass (RYGBP). In 2007, a RYGBP was carried out in 42.1% of all bariatric procedures. Among all patients, 74.4% were female. The mean BMI ranged from 48.5 kg/m2 in 2005 to 48.0 kg/m2 in 2007. Follow-up data after 12 months were available for 63.8% of the patients operated in 2005 and 2006. The mortality was 0.1% (30 days) and 0.16% (overall). CONCLUSION: As indicated by the worldwide trend, there is an ongoing change from GB to sleeve gastrectomy (SG) and malabsorptive procedures. The BMI of German bariatric surgical patients is substantially higher than that of patients from most other countries. There were no differences in overall outcomes during follow-up as compared to published studies.