Population studies have linked insulin resistance to systemic low-grade chronic inflammation and have reported elevated levels of inflammatory cytokines such as TNFα, IL-1β and IL-6, individually or in certain combinations, in adipose tissues or in the serum. We undertook this comprehensive study to simultaneously evaluate the expression of several pro-inflammatory and anti-inflammatory cytokines in serum and in the visceral and subcutaneous adipose tissues from obese patients undergoing bariatric surgery. We observed that several inflammatory cytokines implicated in obesity-associated inflammation showed no significant difference in protein or gene expression between obese patients with or without diabetes and control groups. IL1B gene expression was significantly elevated in the visceral adipose tissues of obese patients, but did not correlate with their diabetes status. Despite the significant increase in IL1B expression in the obese group, a significant proportion of obese patients did not express TNFA, IL1B or IL6 in visceral adipose tissues. Certain inflammatory cytokines showed correlation with the chemokine CCL2 and VEGF-A in visceral adipose tissues. Our findings suggest that the inflammatory cytokine profile in metabolic syndrome is more complex than what is currently perceived and that chronic inflammation in obese patients likely results from incremental contribution from different cytokines and possibly other inflammatory mediators from within and outside the adipose tissues. It is possible that this obesity associated chronic inflammation is not predicted by a single mediator, but rather includes a large spectrum of possible profiles.

Objectives: Craniopharyngiomas are rare low-grade tumors located in the hypothalamic and/or pituitary region. Hypothalamic involvement and treatment resulting in hypothalamic damage are known to lead to development of "hypothalamic obesity" (HyOb) in 50% of cases. The management of HyOb, associated with eating disorders and rapid comorbidities, is an important issue. Bariatric surgery is the most effective therapy for weight loss in patients with severe exogenous obesity. The aim of this systematic review and meta-analysis was to determine the 12-month outcome of bariatric surgery for HyOb due to craniopharyngioma treatment. Methods and Results:Relevant studies were identified by searches of the MEDLINE and EMBASE databases until January 2013. A total of 21 cases were included: 6 with adjustable gastric banding, 8 with sleeve gastrectomy, 6 with Roux-en-Y gastric bypass, and 1 with biliopancreatic diversion. After data pooling, mean weight difference was Ϫ20.9 kg after 6 months (95% confidence interval [CI], Ϫ35.4, Ϫ6.3) and Ϫ15.1 kg after 12 months (95% CI, Ϫ31.7, ϩ1.4). The maximal mean weight loss was achieved by the gastric bypass group: Ϫ31.0 kg (95% CI, Ϫ77.5, ϩ15.5) and Ϫ33.7 kg (95% CI, Ϫ80.7, ϩ13.3) after 6 and 12 months, respectively. Conclusions:In this largest ever published study on the effect of bariatric surgery on obesity after craniopharyngioma treatment, we observed an important weight loss after 1 year of follow-up. Larger studies are warranted to establish appropriate selection criteria and the best surgical technique to perform bariatric surgery. (J Clin Endocrinol Metab 98: 2239 -2246, 2013) C raniopharyngiomas are benign, slow-growing tumors that are located within the sellar and parasellar region of the central nervous system. There are 2 histological types: the adamantinomatous tumors, mostly seen in children, which arise from epithelial remnants of the Rathke's pouch; and the squamous papillary form, seen in adults. The incidence rate ranges from 0.5 to 2 per million subjects/year, with a peak between 5 and 14 years of age, although craniopharyngiomas can occur at any age (1).Tumor resection, with or without radiotherapy, represents the therapeutic standard of care. After treatment, obesity and eating disorders are observed in 40 -50% of patients (2-4). Weight gain is also observed at diagnosis before treatment in some patients. Risk factors for the development of obesity after treatment of craniopharyngioma include younger age at diagnosis, presence of endocrinopathy whatever type, initial symptoms of intracranial hypertension, greater body mass index (BMI) at diagnosis, familial predisposition for obesity, and hypothalamic involvement. In addition, pterional surgery, multiple surgery, and hypothalamic irradiation with doses greater than 51 Gy have been associated with the development of obesity (3,(5)(6)(7).The cause of weight gain in this setting is incompletely understood, but it is believed to be due to "endogenous" mechanisms, rather than the more common form of "exogenous" obesit...

Gonadotrophin deficiency is a common finding in adolescents with PSIS and is frequently associated with other PHDs. However its severity is variable, ranging from complete gonadotrophin deficiency to normogonadotrophic amenorrhoea. The occurrence of gonadotrophin deficiency in 33% of children with apparently isolated GHD and PSIS has important implications for the counselling and follow-up of these patients.

To enhance efficacy of forthcoming type 1 diabetes (T1D) clinical trials, combination therapies (CTs) are envisaged. In this study, we showed that efficacy of a CT, using anti-CD3 antibody and glutamic acid decarboxylase of 65 kd (GAD65)-expressing plasmid, to reverse new-onset T1D was dependent upon the genetic background. Synergism between both treatments was only observed in the RIP-LCMV-GP but not in the nonobese diabetic (NOD) or RIP-LCMV-NOD models. Efficacy was associated with an expansion of bystander suppressor regulatory T cells (Tregs) recognizing the C-terminal region of GAD65 and secreting interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and interferon-γ (IFN-γ). In addition, we found that frequency and epitope specificity of GAD65-reactive CD4+ T cells during antigen priming at diabetes onset and Tregs detected after CT correlated. Consequently, NOD mice harbored significantly lower levels of GAD65-reactive CD4+ T cells than RIP-LCMV-GP before and after treatment. Our results demonstrate that antigen-specific T cells available at treatment may differ between various major histocompatibility complex (MHC) and genetic backgrounds. These cells play a major role in shaping T-cell responses following antigen-specific immune intervention and determine whether a beneficial Tregs response is generated. Our findings hold important implications to understand and predict the success of antigen-based clinical trials, where responsiveness to immunotherapy might vary from patient to patient.