Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). Steatosis, the hallmark feature of NAFLD, occurs when the rate of hepatic fatty acid uptake from plasma and de novo fatty acid synthesis is greater than the rate of fatty acid oxidation and export (as triglyceride within VLDL). Therefore, an excessive amount of intrahepatic triglyceride represents an imbalance between complex interactions of metabolic events. The presence of steatosis is associated with a constellation of adverse alterations in glucose, fatty acid and lipoprotein metabolism. It is likely that abnormalities in fatty acid metabolism, in conjunction with adipose tissue, hepatic, and systemic inflammation, are key factors involved in the development of insulin resistance, dyslipidemia and other cardiometabolic risk factors associated with NAFLD. However, it is not clear whether NAFLD causes metabolic dysfunction or whether metabolic dysfunction is responsible for IHTG accumulation, or possibly both. Understanding the precise factors involved in the pathogenesis and pathophysiology of NAFLD will provide important insights into the mechanisms responsible for the cardiometabolic complications of obesity.

Nonalcoholic Fatty Liver Disease (NAFLD) is the hepatic manifestation of metabolic syndrome, and its rising prevalence parallels the rise in obesity and diabetes. Historically thought to result from overnutrition and sedentary lifestyle, recent evidence suggests that diets high in sugar (from sucrose and/or high fructose corn syrup (HFCS)) not only increases the risk for NAFLD, but also, nonalcoholic steatohepatitis (NASH). Here we review the experimental and clinical evidence that fructose precipitates fat accumulation in the liver, due to both increased lipogenesis and impaired fat oxidation. Recent evidence suggests that the predisposition to fatty liver is linked with metabolism of fructose by fructokinase C, resulting in ATP consumption, nucleotide turnover and uric acid generation that mediate fat accumulation. Alterations in gut permeability, microbiome, and associated endotoxemia contributes to the risk of NAFLD and NASH. Early clinical studies suggest that reducing sugary beverages and total fructose intake, especially from added sugars, may have a significant benefit on reducing hepatic fat accumulation. We suggest larger, more definitive trials to determine if lowering sugar/HFCS intake, and/or blocking uric acid generation, may help reduce NAFLD and its downstream complications of cirrhosis and chronic liver disease.

Nonalcoholic fatty liver disease (NAFLD) and alterations in hepatic lipoprotein kinetics are common metabolic complications associated with obesity. Lifestyle modification involving diet-induced weight loss and regular exercise decreases intrahepatic triglyceride (IHTG) content and very low density lipoprotein (VLDL) triglyceride (TG) secretion rate. The aim of this study was to evaluate the weight loss-independent effect of following the physical activity guidelines recommended by the Department of Health and Human Services on IHTG content and VLDL kinetics in obese persons with NAFLD. Eighteen obese people (BMI: 38.1 ± 4.6 kg/m2) with NAFLD were randomized to 16 weeks of exercise training (45-55% V̇O2peak, 30-60 min × 5 days/week; n = 12) or observation (control; n = 6). Magnetic resonance spectroscopy and stable isotope tracer infusions in conjunction with compartmental modeling were used to evaluate IHTG content and hepatic VLDL-TG and apolipoprotein B-100 (apoB-100) secretion rates. Exercise training resulted in a 10.3 ± 4.6 % decrease in IHTG content (p<0.05), but did not change total body weight (103.1 ± 4.2 kg before and 102.9 ± 4.2 kg after training) or percent body fat (38.9 ± 2.1 % before and 39.2 ± 2.1 % after training). Exercise training did not change the hepatic VLDL-TG secretion rate (17.7 ± 3.9 μmol/min before and 16.8 ± 5.4 μmol/min after training) or VLDL-apoB-100 secretion rate (1.5 ± 0.5 nmol/min before and 1.6 ± 0.6 nmol/min after training). Conclusions: Following the Department of Health and Human Services recommended physical activity guidelines has small but beneficial effects on IHTG content, but does not improve hepatic lipoprotein kinetics, in obese persons with NAFLD.

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ObjectiveRoux-en-Y gastric bypass (RYGB) surgery causes greater weight loss than laparoscopic adjustable gastric banding (LAGB). We tested the hypothesis that RYGB has weight loss-independent effects on taste perception which influence eating behavior and contribute to the greater weight loss.Design and MethodsSubjects were studied before and after ~20% weight loss induced by RYGB (n=17) or LAGB (n=10). We evaluated: taste sensitivity for sweet, salty and savory stimuli; sucrose and monosodium glutamate (MSG) preferences; sweetness palatability; eating behavior; and expression of taste-related genes in biopsies of fungiform papillae.ResultsWeight loss induced by both procedures caused the same decrease in: preferred sucrose concentration (−12±10%), perceived sweetness of sucrose (−7±5%), cravings for sweets and fast-foods (−22 ±5%), influence of emotions (−27±5%) and external food cues (−30±4%) on eating behavior, and expression of α-gustducin in fungiform papillae (all P-values <0.05). RYGB, but not LAGB, shifted sweetness palatability from pleasant to unpleasant when repetitively tasting sucrose (P=0.05). Neither procedure affected taste detection thresholds or MSG preferences.ConclusionsLAGB and RYGB cause similar alterations in eating behaviors, when weight loss is matched. These changes in eating behavior were not associated with changes in taste sensitivity, suggesting other, as yet unknown, mechanisms are involved.

Remimazolam can be administered safely under the supervision of endoscopists for outpatient colonoscopy, and it allows faster recovery of neuropsychiatric function compared with placebo (midazolam rescue) and midazolam. (Clinical trial registration number: NCT02290873.).

Objective: Personality influences lifestyle behaviors. Therefore, certain personality traits could contribute to obesity and the response to behaviorally based weight loss therapy. Purpose: The aims of this study were to test the hypothesis that personality characteristics differ between lean and obese persons in the community, obese persons in the community and obese persons seeking weight loss therapy by enrolling in a comprehensive weight loss program, and in obese persons who were successful and unsuccessful in achieving behavioral therapy-induced weight loss. Methods: The Temperament and Character Inventory was administered to 264 lean (body mass index (BMI) o25 kg/m 2 ) and 56 obese (BMIX35 kg/m 2 ) subjects from the St Louis community and 183 obese patients (BMI ¼ 44710 kg/m 2 ) enrolled in the Washington University Weight Management Program (WUWMP), which involved weekly group behavioral therapy and diet education sessions for 22 weeks. Results: Compared with lean subjects, obese subjects in the community scored higher in novelty seeking (19.775.9 vs 16.276.0, Po0.05), lower in Persistence (4.171.8 vs 4.871.7, Po0.05) and lower in self-directedness (32.177.6 vs 34.376.6, Po0.05.) Patients enrolled in the WUWMP scored higher than obese persons in the general population in both Reward Dependence (17.174.2 vs 15.774.3, Po0.05) and cooperativeness (36.975.4 vs 34.576.2, Po0.05). Patients who were successful in losing weight (410% weight loss) after 22 weeks of behavioral therapy scored lower in novelty seeking than those who were unsuccessful in losing weight (o5% weight loss) (17.675.9 vs 20.275.9, Po0.05). Discussion: These results suggest that personality traits differ between lean and obese persons, and between obese persons who enroll and who do not enroll in a comprehensive weight management program. Moreover, high scores in novelty seeking are associated with decreased success in achieving behavioral therapy-induced weight loss.

Our meta-analysis indicates that targeted biopsies with acetic acid chromoendoscopy, electronic chromoendoscopy by using narrow-band imaging, and endoscope-based CLE meet the thresholds set by the ASGE PIVI, at least when performed by endoscopists with expertise in advanced imaging techniques. The ASGE Technology Committee therefore endorses using these advanced imaging modalities to guide targeted biopsies for the detection of dysplasia during surveillance of patients with previously nondysplastic BE, thereby replacing the currently used random biopsy protocols.