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Pisani D.F.,University of Nice Sophia Antipolis | Pisani D.F.,French National Center for Scientific Research | Pisani D.F.,French Institute of Health and Medical Research | Beranger G.E.,University of Nice Sophia Antipolis | And 32 more authors.
FASEB Journal | Year: 2016

Brown adipose tissue (BAT) is essential for adaptive thermogenesis and dissipation of caloric excess through the activity of uncoupling protein (UCP)-1.BATin humans is of great interest for thetreatment of obesityand related diseases. In this study, the expression of Twikrelated acid-sensitive K+ channel (TASK)-1 [a pH-sensitive potassium channel encoded by the potassium channel, 2-pore domain, subfamily K,member 3 (Kcnk3) gene] correlated highly with Ucp1 expression in obese and coldexposedmice. In addition, Task1-nullmice, compared with their controls, became overweight, mainly because of an increase in white adipose tissue mass and BAT whitening. Task1-/--mouse-derived brown adipocytes, compared with wild-typemouse-derived brown adipocytes, displayed an impaired β3-adrenergic receptor response that was characterized by a decrease in oxygen consumption, Ucp1 expression, and lipolysis. This phenotype was thought tobe caused by an exacerbation of mineralocorticoid receptor (MR) signaling, given that it was mimicked by corticoids and reversed by an MR inhibitor. We concluded that the K+ channel TASK1 controls the thermogenic activity in brown adipocytes through modulation of β-adrenergic receptor signaling. © FASEB.

Ritz P.,Toulouse University Hospital Center | Ritz P.,University Paul Sabatier | Topart P.,Clinique de lAnjou | Benchetrit S.,Center Pericaud | And 7 more authors.
Surgery for Obesity and Related Diseases | Year: 2014

Background: The benefits and risks of bariatric surgery are debated in older patients. The objective of this study was to compare the weight changes and adverse outcomes in patients>60 years and in younger ones. Methods: The French SOFFCO registry was screened for gastric bypass (RYGB), gastric banding (LAGB), or sleeve gastrectomy (SG) performed between 2007 and 2010. Adverse outcomes and weight changes (%) over 12 months were compared between patients<40 years (N = 1379), between 40-59 years (N = 1065), and>60 years (N = 164). Results: After a RYGB surgical (12.3 versus 3.8%; P = .03) and nonsurgical (7.0% versus .8%; P = .01) complications were more prevalent in patients above 60 years than in those below 40. No increased prevalence of surgical and nonsurgical complications was seen after a LAGB or a SG. Weight loss (% of initial weight) was lower after a LAGB than after a RYGB or a SG. After LAGB weight loss (%) did not differ between patients above 60 years and those aged<40 (difference 1.7±1.5%, P = .26). After a RYGB weight loss (%) was lower in patients aged>60 years (-5.6±1.7%, P = .001) than in those aged<40 years. After a SG, weight loss (%) was lower in patients aged>60 years (-7.0±2.6%, P = .01) than in those aged<40 years. Conclusion: Bariatric surgery can be a short-term effective and safe therapeutic option in elderly patients. LAGB or SG appears to be an alternative strategy to RYGB, with lower adverse outcome rate. © 2014 American Society for Bariatric Surgery.

Noppe G.,Section of Endocrinology | Noppe G.,Sophia Childrens Hospital | Noppe G.,Obesity Center | Van Rossum E.F.C.,Section of Endocrinology | And 8 more authors.
Hormone Research in Paediatrics | Year: 2014

Background: Cortisol is produced in a circadian rhythm controlled by the hypothalamus-pituitary-adrenal axis, making it cumbersome to measure long-term cortisol exposure. Hair has proven to be a reliable matrix for long-term cortisol measurement in adults and can be used as diagnostic tool for (cyclic) Cushing's syndrome. The diagnostic applicability in children has not been studied, nor have the effects of development and hair care been evaluated in children. We aimed to establish reference ranges of hair cortisol concentrations (HCC) in healthy children and to evaluate the effects of age, gender, puberty and characteristics of hair care. Methods: In 128 healthy children aged 4-14 years, HCC were measured in a small 3-cm hair lock from the back of the head. Results: HCC increased with age (p = 0.04) up to age 10 years, with a mean of 5.0, 5.8, 6.8 and 8.5 pg/mg at age 4-5, 6-7, 8-9 and 10-14 years, respectively. Children aged 4-7 years had significantly lower HCC compared to healthy adults (p = 0.007). We did not find any influence of gender, puberty or hair care characteristics on hair cortisol. Conclusion: HCC can be reliably measured in childhood, and reference ranges increase with age. HCC in children are not dependent on hair care or hair characteristics. © 2014 S. Karger AG, Basel.

Han S.-M.,CHA Medical University | Kim W.W.,Obesity Center | Moon R.,Cleveland Clinic | Rosenthal R.J.,Cleveland Clinic
Obesity Surgery | Year: 2013

Laparoscopic sleeve gastrectomy (LSG) is an effective procedure for treating morbid obesity, and the majority of female patients who received LSG were at childbearing age. Female patients, who successfully lost weight following LSG and became pregnant, need to be evaluated carefully. Information was gathered, through prospectively maintained database and phone interview, on women who underwent LSG from May 2003 to July 2011. A total of 136 women underwent LSG in this period. There were 13 (9.6 %) pregnancies in 12 patients after LSG. The age before surgery was 28.3 ± 4.0. The mean weight and body mass index (BMI) before LSG were 95.3 ± 9.4 kg and 35.1 ± 3.5 kg/m2, respectively. The average time from LSG to the first live birth was 32.0 ± 19.1 months. Mean BMI decreased significantly after LSG, from 35.1 ± 3.5 to 24.9 ± 2.3 kg/m2 at conception. The mean percentage of excess body mass index loss was 85.8 ± 16.7 % at conception and 42.7 ± 25.1 % at delivery. Gained weight during pregnancy was 15.1 ± 5.2 kg. The mean gestational age and birth weight were 39.0 ± 1.6 weeks and 3,229.0 ± 505.9 g. In two cases (15.4 %), cesarean section was performed. No cases of pregnancy-induced hypertension and diabetes developed. Major congenital anomalies and neonatal deaths were not recorded. Larger study with longer follow-up is needed to evaluate the effect of LSG in pregnancies. However, these findings show that LSG seems to be a safe option for morbidly obese women in their reproductive period. © 2013 Springer Science+Business Media New York.

Matsuo Y.,University of Leipzig | Matsuo Y.,Takasaki General Medical Center | Matsuo Y.,Gunma University | Oberbach A.,University of Leipzig | And 13 more authors.
Obesity | Year: 2013

Objective HDL regulates endothelial function via stimulation of nitric oxide production. It is documented that endothelial function is impaired in obese adolescents, and improved by lifestyle interventions (LI). Design and Methods HDL function in obese adolescents and the impact of LI or Roux-en-Y gastric bypass surgery (RYGB) was assessed. HDL was isolated from 14 adolescents with normal body mass index (HDLcontrol), 10 obese (HDL obese) before and after 6 month LI, and five severe obese adolescents before and one year after RYGB. HDL-mediated phosphorylation of endothelial nitric oxide synthase (eNOS)-Ser1177, eNOS-Thr495, and PKC-ßII was evaluated. In addition the HDL proteome was analyzed. Results HDLobese-mediated eNOS-Ser1177 phosphorylation was reduced, whereas eNOS-Thr495 phosphorylation increased significantly when compared to HDLcontrol. No impact of obesity was observed on PKC-ßII phosphorylation. LI and RYGB had no impact on HDL-mediated phosphorylation of eNOS and PKC-ßII. A principle component plot analysis of the HDL particle separated controls and severe obese, whereas the interventions did not trigger sufficient differences to the HDL proteome to permit distinction. Conclusion These results demonstrated that HDL-function is impaired in obese adolescents, and that LI or RYGB did not correct this dysfunction. This might be an argument for developing earlier prevention strategies in obese adolescents to avoid HDL dysfunction. Copyright © 2013 The Obesity Society.

Abramo A.,Anestesia e Rianimazione Universitaria | Di Salvo C.,Anestesia e Rianimazione Universitaria | Baldi G.,Anestesia e Rianimazione Universitaria | Marini E.,Anestesia e Rianimazione Universitaria | And 4 more authors.
Obesity Surgery | Year: 2012

Background: Anesthesia is able to modulate the balance between proinflammatory and anti-inflammatory cytokine production during surgery. The aim of this study is to assess the effect of three anesthesia approaches, total intravenous anesthesia (TIVA), inhalation anesthesia, and xenon anesthesia, on sieric levels of nitric oxide (NO), IL6, IL10, and TNFα in obese patients undergoing Roux-en-Y laparoscopic gastric bypass. Methods: Thirty adult morbidly obese patients (BMI > 35) scheduled for Roux-en-Y laparoscopic gastric bypass were randomly recruited and allocated to TIVA (N = 10), inhalation anesthesia (SEV, N = 10), and xenon anesthesia (XE, N = 10). Exclusion criteria were ASA IV, age <18 or >60 years, and Mallampati IV. Opioid dosage and ventilation parameters were standardized. Sieric levels of NO, IL6, IL10, and TNFα were assessed at T0 (before induction of anesthesia), T1 (end of surgery), and T2 (12 h after the end of surgery). We compared the relative cytokine level variations (delta) at T1 and T2 and the cytokine exposure levels calculated as the area under the curve (AUC) between T0 and T2 in the XE and non-XE (SEV + TIVA) groups. Results: At T1, we found a significant ΔIL10 (reduction) and ΔTNFα (reduction) between XE and SEV (p < 0.05) and XE and TIVA (p < 0.05) groups. At T2, ΔIL10 was still significant. Furthermore, we found a reduced AUC value for TNFα in the XE group. Conclusions: Xenon anesthesia seems able to inhibit postoperative proinflammatory cytokine imbalance in morbidly obese patients undergoing Roux-en-Y laparoscopic gastric bypass; the reduced ΔTNFα at T1 and the reduced global exposition to TNFα in the XE group may explain the reduced ΔIL10 at T1 and T2. © 2011 Springer Science + Business Media, LLC.

Gall J.M.,Boston Medical Center | Wang Z.,Boston Medical Center | Bonegio R.G.,Boston Medical Center | Havasi A.,Boston Medical Center | And 4 more authors.
Journal of the American Society of Nephrology | Year: 2015

Proximal tubule (PT) cells are critical targets of acute ischemic injury. Elimination of the mitochondrial fusion protein mitofusin 2 (Mfn2) sensitizes PT cells to apoptosis in vitro. However, the role of PT Mfn2 in ischemic AKI in vivo is unknown. To test its role, we evaluated the effects of conditional KO of PT Mfn2 (cKO-PT-Mfn2) on animal survival after transient bilateral renal ischemia associated with severe AKI. Forty-eight hours after ischemia, 28% of control mice survived compared with 86% of cKO-PT-Mfn2 animals (P<0.001 versus control). Although no significant differences in histologic injury score, apoptosis, or necrosis were detected between genotypes, cKO-PT-Mfn2 kidneys exhibited a 3.5-fold increase in cell proliferation restricted to the intrarenal region with Mfn2 deletion. To identify the signals responsible for increased proliferation, primary PT cells with Mfn2 deficiency were subjected to stress by ATP depletion in vitro. Compared with normal Mfn2 expression, Mfn2 deficiency significantly increased PT cell proliferation and persistently activated extracellular signal-regulated kinase 1/2 (ERK1/2) during recovery from stress. Furthermore, stress and Mfn2 deficiency decreased the interaction between Mfn2 and Ras detected by immunoprecipitation, and purified Mfn2 dose-dependently decreased Ras activity in a cell-free assay. Ischemia in vivo also reduced the Mfn2-RAS interaction and increased both RAS and p-ERK1/2 activity in the renal cortical homogenates of cKO-PT-Mfn2 mice. Our results suggest that, in contrast to its proapoptotic effects in vitro, selective PT Mfn2 deficiency accelerates recovery of renal function and enhances animal survival after ischemic AKI in vivo, partly by increasing Ras-ERK-mediated cell proliferation. Copyright © 2015 by the American Society of Nephrology.

Langerak T.,Rotterdam University | Langerak T.,Obesity Center | Van Den Dries L.W.J.,Rotterdam University | Wester V.L.,Rotterdam University | And 8 more authors.
Clinical Endocrinology | Year: 2015

Objective Patients infected with the human immunodeficiency virus (HIV) have an increased risk of metabolic complications such as dyslipidaemia, insulin resistance and hypertension; symptoms that are also associated with an excess of the hormone cortisol. We studied the relationship between long-term cortisol levels and metabolic syndrome (MetS) in HIV-infected patients. Design Cross-sectional study performed at the outpatient clinic of infectious diseases of the Erasmus MC, University Medical Center Rotterdam, the Netherlands. Methods Fasting blood samples and anthropometric data were collected in 126 HIV-infected patients. An ELISA-based technique was used to determine long-term cortisol levels in scalp hair. Cortisol levels were compared to 191 healthy controls. Results A higher risk of MetS was observed in HIV patients with a low hair cortisol (odds ratio lower vs upper tertile 4·23, P = 0·04). Hair cortisol levels were not significantly different between HIV patients and healthy controls (16·4 pg/mg vs 13·5 pg/mg; P = 0·14). Conclusion The risk of MetS was significantly higher in HIV-infected patients in the lowest hair cortisol group compared with patients in the highest hair cortisol group. This finding contrasts with results from studies in uninfected individuals where a high cortisol level in hair is associated with metabolic syndrome. The results of this study suggest that these metabolic complications might be related to relative cortisol hypersensitivity in HIV patients. © 2015 John Wiley & Sons Ltd.

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