Antonio Iannelli

Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients.

T-cell regulation in adipose tissue provides a link between inflammation and insulin resistance. Because of alterations in adipose tissue T-cell composition in obesity, we aimed to identify the antigen-presenting cells in adipose tissue of obese mice and patients with insulin resistance. Dendritic cells (DCs) and T cells were studied in mice and in two cohorts of obese patients. In lean mice, only CD11c+ DCs were detected in adipose tissue. Adoptive transfer of naive CD4+ T cells in Rag1−/− mice led to a predominant Th1 response in adipose tissue. In contrast, during obesity DCs (human CD11c+CD1c+ and mouse CD11chighF4/80low) accumulated in adipose tissue. CD11chighF4/80low DCs from obese mice induced Th17 differentiation. In patients, the presence of CD11c+CD1c+ DCs correlated with the BMI and with an elevation in Th17 cells. In addition, these DCs led to ex vivo Th17 differentiation. CD1c gene expression further correlated with homeostatic model assessment-insulin resistance in the subcutaneous adipose tissue of obese patients. We show for the first time the presence and accumulation of specific DCs in adipose tissue in mouse and human obesity. These DCs were functional and could be important regulators of adipose tissue inflammation by regulating the switch toward Th17 cell responses in obesity-associated insulin resistance.

Internal Hernia after Laparoscopic Roux-en-Y Gastric Bypass for Morbid Obesity

Background: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) is associated with a relatively high incidence of internal hernias (IH) when compared to the open operation. Methods: A search in PubMed MEDLINE from January 1994 through January 2006 was performed (keywords: obesity, laparoscopy, gastric bypass and internal hernia). Results: 26 studies with a total of 11,918 patients were considered. 300 cases of IH occurred (rate 2.51%). IH occurred 116 times at the level of the transverse colon mesentery (69%), 30 at the Petersens space (18%), and 22 at the entero-enterostomy site (13%). 142 re-operations were performed laparoscopically (85.6%), and 24 by laparotomy (14.4%). Bowel resection was done in 5 cases (4.7%). Mortality was 1.17%. Conclusions: IH after LRYGBP has an incidence of 2.51%. Closure of mesenteric defects with non-absorbable running suture and antecolic Roux limb are recommended. Surgical exploration for suspicion of IH after LRYGBP should be first done by laparoscopy.

The inflammatory C-reactive protein is increased in both liver and adipose tissue in severely obese patients independently from metabolic syndrome, Type 2 diabetes, and NASH.

OBJECTIVE:C-Reactive Protein (CRP), a nonspecific marker of inflammation that is moderately elevated in obesity, metabolic syndrome (MS), and type 2 diabetes, has been proposed as a surrogate marker of nonalcoholic steatohepatitis (NASH). Its clinical usefulness in the diagnosis of NASH was evaluated in severely obese patients without or with MS, diabetes, and NASH and the potential roles of the liver and of the adipose tissue in CRP production were characterized.METHODS:Severely obese patients without NASH (without MS [N = 13], with MS [N = 11], or with MS and diabetes [N = 7]) and with NASH (without [N = 8] or with [N = 7] MS) were studied. For each patient, liver and adipose tissue biopsies were collected during a bariatric surgery and were used to determine the CRP gene expression by real-time PCR. The role of interleukin-6 (IL6) and lipopolysaccharide in CRP expression was also evaluated in subcutaneous adipose tissue obtained during cosmetic abdominoplasty.RESULTS:Plasma CRP levels were elevated in severely obese patients independently from the presence or absence of MS, diabetes, or NASH. CRP gene expression was not only increased in livers but also in adipose tissues of obese patients compared with controls subjects. In human adipose tissue, CRP mRNA levels were positively correlated with those of IL-6 and the CRP expression was enhanced in vitro by IL-6 and lipopolysaccharide.CONCLUSION:Plasma CRP levels are not predictive of the diagnosis of NASH in severely obese patients. The liver but also the adipose tissue can produce CRP, a process which could be dependent on IL6. Therefore, both tissues might contribute to the elevated plasma CRP levels found in obesity. In addition, the large amount of body fat may well produce an important part of the circulating CRP, further limiting its clinical usefulness in the evaluation of NASH in severely obese patients.

Mast cells and cellularity of the colonic mucosa correlated with fatigue and depression in irritable bowel syndrome

Background: A subset of patients with irritable bowel syndrome (IBS) have an increased number of mast cells (MCs) in the colonic mucosa. Psychological factors are believed to contribute to the course of IBS. Aims: To examine associations between fatigue, depression and MCs of the colonic mucosa in IBS. Methods: Colonic biopsies were taken from 50 Rome II IBS patients, 21 healthy controls and 11 depressed/fatigued patients without IBS. The cellularity of the lamina propria was determined as the number of inflammatory cells per high power field (hpf) through a 400× microscope. The Fatigue Impact Scale (FIS) and the short form Beck Depression Inventory (BDI) evaluated the severity of fatigue and depression. Results: IBS patients had a significant increase in the cellularity of the lamina propria compared with controls or with depressed patients (mean (SD) 94.5 (48–110) vs 68 (58–82) and 78 (87–90) cells per hpf, p = 0.005 and p = 0.05, respectively), in particular of MCs (9.3 (5.6–11.7) vs 4.0 (2.7–6.8) and 4.3 (2.8–7.8) cells per hpf, p = 0.001 and p = 0.005, respectively). Both the FIS and BDI scores were significantly higher in IBS or in depressed patients than in controls (p<0.001). In IBS, the FIS score correlated significantly with the cellularity of the lamina propria (r = 0.51, p<0.0001) and MCs (r = 0.64, p<0.0001). In IBS, the BDI score correlated significantly with MCs (r = 0.29, p = 0.03). Conclusions: Elevated MCs counts are a key feature of the low-grade inflammatory infiltrate in the caecal mucosa of IBS. Fatigue and depression are associated with mucosal cell counts, in particular MCs, suggesting that psychological factors are associated with the low-grade inflammatory infiltrate in IBS.

Hepatic expression patterns of inflammatory and immune response genes associated with obesity and NASH in morbidly obese patients.

Background Obesity modulates inflammation and activation of immune pathways which can lead to liver complications. We aimed at identifying expression patterns of inflammatory and immune response genes specifically associated with obesity and NASH in the liver of morbidly obese patients. Methodology/Principal Findings Expression of 222 genes was evaluated by quantitative RT-PCR in the liver of morbidly obese patients with histologically normal liver (n = 6), or with severe steatosis without (n = 6) or with NASH (n = 6), and in lean controls (n = 5). Hepatic expression of 58 out of 222 inflammatory and immune response genes was upregulated in NASH patients. The most notable changes occurred in genes encoding chemokines and chemokine receptors involved in leukocyte recruitment, CD and cytokines involved in the T cell activation towards a Th1 phenotype, and immune semaphorins. This regulation seems to be specific for the liver since visceral adipose tissue expression and serum levels of MCP1, IP10, TNFα and IL6 were not modified. Importantly, 47 other genes were already upregulated in histologically normal liver (e.g. CRP, Toll-like receptor (TLR) pathway). Interestingly, serum palmitate, known to activate the TLR pathway, was increased with steatosis. Conclusion/Significance The liver of obese patients without histological abnormalities already displayed a low-grade inflammation and could be more responsive to activators of the TLR pathway. NASH was then characterized by a specific gene signature. These findings help to identify new potential actors of the pathogenesis of NAFLD.

A new composite model including metabolic syndrome, alanine aminotransferase and cytokeratin-18 for the diagnosis of non-alcoholic steatohepatitis in morbidly obese patients

Aliment Pharmacol Ther 2010; 32: 1315–1322

Regular coffee but not espresso drinking is protective against fibrosis in a cohort mainly composed of morbidly obese European women with NAFLD undergoing bariatric surgery

BACKGROUND & AIMS The aim of this study was to determine the influence of coffee and other caffeinated drinks on liver fibrosis of severely obese European patients. METHODS A specific questionnaire exploring various types of coffee (regular filtrated coffee and espresso), caffeinated drinks, and chocolate was filled in by 195 severely obese patients. All patients had liver biopsies that were analyzed according to the NASH Clinical Research Network Scoring System. Univariate and multivariate analyses of significant fibrosis were performed. RESULTS Caffeine came mainly from coffee-containing beverages (77.5%). Regular coffee and espresso were consumed in 30.8% and 50.2% of the patients, respectively. Regular coffee, espresso, and total caffeine consumption was similar between patients with and without NASH. While consumption of espresso, caffeinated soft drinks, and chocolate was similar among patients, with respect to the level of fibrosis, regular coffee consumption was lower in patients with significant fibrosis (F ≥2). According to logistic regression analysis, consumption of regular coffee was an independent protective factor for fibrosis (OR: 0.752 [0.578-0.980], p=0.035) in a model including level of AST (OR: 1.04 [1.004-1.076], p=0.029), presence of NASH (OR: 2.41 [1.007-5.782], p=0.048), presence of the metabolic syndrome (NS), and level of HOMA-IR (NS). Espresso, but not regular coffee consumption was higher in patients with lower HDL cholesterol level, higher triglyceride level, and the metabolic syndrome. CONCLUSIONS Consumption of regular coffee but not espresso is an independent protective factor for liver fibrosis in severely obese European patients.

Can laparoscopy reduce hospital stay in the treatment of crohn's disease?

PURPOSE: The aim of this article was to investigate the safety, outcome, length of stay, and cost of hospital admission in patients with Crohns disease who underwent laparoscopy compared with open surgery. METHODS: Among 51 consecutive patients with inflammatory bowel disease (1996–2000), 46 with Crohns disease were included in this nonrandomized prospective study. Of these, 20 patients underwent laparoscopic surgery and 26 underwent open surgery. Data collected included the following information: age, gender, body mass index, diagnosis, duration of disease, preoperative medical treatment, previous abdominal surgery, present indication for surgery, and procedure performed (comparability measures), as well as conversion to open surgery, operating time, time to resolution of ileus, morbidity, duration of hospital stay, and cost of hospital admission (outcome measures). RESULTS: There was no significant difference with respect to comparability measures between the laparoscopic and the open-surgery groups. There was no mortality. There was no intraoperative complication in either group and no conversion in the laparoscopic group. Operating time was significantly longer in the laparoscopic group (302 minutes)vs. the open group (244.7 minutes) (P<0.05), but this difference disappeared when data were adjusted for the extra time required to perform the laparoscopic hand-sewn anastomoses (288.2 minutesvs. 244.7 minutes). Bowel function returned more quickly in the laparoscopic groupvs. the open group in terms of passage of flatus (3.7vs. 4.7 days) (P<0.05) and resumption of oral intake (4.2vs. 6.3 day) (P<0.01). There were significantly fewer postoperative complications in the laparoscopic group (9.5 percent)vs. the open group (18.5 percent) (P<0.05); the length of stay was significantly shorter in the laparoscopic group (8.3 days)vs. the open group (13.2 days) (P<0.01); and the cost of hospital admission was significantly lower in the laparoscopic group (

C-reactive protein levels in relation to various features of non-alcoholic fatty liver disease among obese patients

6106, United States dollars)vs. the open group (

Laparoscopic sleeve gastrectomy and gastroesophageal reflux

9829, United States dollars) (P<0.05). CONCLUSION: There is a reduction in the postoperative ileus, length of stay, cost of hospital admission, and postoperative complication rate in the laparoscopic group. Laparoscopic surgery for Crohns disease is safe, and it is potentially more cost-effective than traditional open surgery.