Adipocyte exosomes induce transforming growth factor beta pathway dysregulation in hepatocytes: a novel paradigm for obesity-related liver disease.

BACKGROUND: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) has been attributed to increased systemic inflammation and insulin resistance mediated by visceral adipose tissue (VAT), although the exact mechanisms are undefined. Exosomes are membrane-derived vesicles containing messenger RNA, microRNA, and proteins, which have been implicated in cancer, neurodegenerative, and autoimmune diseases, which we postulated may be involved in obesity-related diseases. We isolated exosomes from VAT, characterized their content, and identified their potential targets. Targets included the transforming growth factor beta (TGF-ß) pathway, which has been linked to NAFLD. We hypothesized that adipocyte exosomes would integrate into HepG2 and hepatic stellate cell lines and cause dysregulation of the TGF-ß pathway. METHODS: Exosomes from VAT from obese and lean patients were isolated and fluorescently labeled, then applied to cultured hepatic cell lines. After incubation, culture slides were imaged to detect exosome uptake. In separate experiments, exosomes were applied to cultured cells and incubated 48-h. Gene expression of TGF-ß pathway mediators was analyzed by polymerase chain reaction, and compared with cells, which were not exposed to exosomes. RESULTS: Fluorescent-labeled exosomes integrated into both cell types and deposited in a perinuclear distribution. Exosome exposure caused increased tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and integrin ανß-5 expression and decreased matrix metalloproteinase-7 and plasminogen activator inhibitor-1 expression in to HepG2 cells and increased expression of TIMP-1, TIMP-4, Smad-3, integrins ανß-5 and ανß-8, and matrix metalloproteinase-9 in hepatic stellate cells. CONCLUSIONS: Exosomes from VAT integrate into liver cells and induce dysregulation of TGF-ß pathway members in vitro and offers an intriguing possibility for the pathogenesis of NAFLD.

Predicting sleep apnea in morbidly obese adolescents undergoing bariatric surgery.

INTRODUCTION: In adults, the association between obesity and obstructive sleep apnea (OSA) is established, and many are concerned OSA increases surgical risk. Pre-operative screening for OSA is standard, and this is also the case in adolescent bariatric surgery. We noted many of our patients were without significant OSA, despite being obese. We reviewed our experience with screening polysomnography (PSG) to determine any predictive variables or complications. METHODS: All bariatric surgery patients from our hospital who had undergone PSG were included, and were stratified into 'OSA' or 'no OSA' by obstructive apnea-hypopnea index (OAHI), as well as by sex. RESULTS: A total of 49 adolescents enrolled during the study period: 10 males and 39 females. OSA prevalence was 42.9 %; males 80 %, females 33.3 %. Height, weight, body mass index (BMI), and prevalence of hypertension were significantly higher in patients with OSA. By sex, females also had more metabolic syndrome and witnessed apneas, while only weight and BMI remained significant in males. There were no peri-operative complications. CONCLUSIONS: Despite uniform obesity, less than half our adolescents had significant OSA on PSG. As no modeling exists to predict OSA in morbidly obese adolescents, we continue to recommend routine PSG, especially in higher weight and BMI patients, and those with hypertension.

Prevalence of Chronic Gastritis or Helicobacter pylori Infection in Adolescent Sleeve Gastrectomy Patients Does Not Correlate with Symptoms or Surgical Outcomes.

BACKGROUND: In adults undergoing gastric bypass surgery, it is routine practice to perform pre-operative testing for Helicobacter pylori infection. Evidence suggests that infection impairs anastomotic healing and contributes to complications. There currently are no data for adolescents undergoing bariatric procedures. Despite few patients with pre-operative symptoms, we noted occasional patients with H. pylori detected after sleeve gastrectomy. We reviewed our experience with our adolescent sleeve gastrectomy cohort to determine the prevalence of H. pylori infection, its predictive factors, and association with outcomes. We hypothesized that H. pylori infection would be associated with pre-operative symptoms, but not surgical outcomes. METHODS: All patients undergoing sleeve gastrectomy at our hospital were included. We conducted a chart review to determine pre- or post-operative symptoms of gastroesophageal reflux disease GERD or gastritis, operative complications, and long-term anti-reflux therapy after surgery. Pathology reports were reviewed for evidence of gastritis and H. pylori infection. RESULTS: 78 adolescents had laparoscopic sleeve gastrectomy from January 2010 through July 2014. The prevalence of chronic gastritis was 44.9% (35/78) and 11.4% of those patients had H. pylori (4/35). Only one patient with H. pylori had pre-operative symptoms, and only 25.7% (9/35) of patients with pathology-proven gastritis had symptoms. One staple line leak occurred but this patient did not have H. pylori or gastritis. Mean patient follow-up was 10 (3-26) mos. CONCLUSIONS: There is a moderate prevalence of gastritis among adolescents undergoing sleeve gastrectomy, but only a small number of these patients had H. pylori infection. Neither the presence of chronic gastritis nor H. pylori infection correlated with symptoms or outcomes. Thus, in the absence of predictive symptomology or adverse outcome in those who are infected, we advocate for continued routine pathologic evaluation without the required need for pre-operative determination unless or until H. pylori infection is associated with adverse surgical outcomes.