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Abdesselem H.,Foundation Medicine | Madani A.,Foundation Medicine | Hani A.,Foundation Medicine | Al-Noubi M.,Foundation Medicine | And 13 more authors.
Journal of Biological Chemistry | Year: 2016

The expansion of fat mass in the obese state is due to increased adipocyte hypertrophy and hyperplasia. The molecular mechanism that drives adipocyte hyperplasia remains unknown. The NAD+-dependent protein deacetylase sirtuin 1 (SIRT1), a key regulator of mammalian metabolism, maintains proper metabolic functions in many tissues, counteracting obesity. Here we report that differentiated adipocytes are hyperplastic when SIRT1 is knocked down stably in mouse 3T3-L1 preadipocytes. This phenotype is associated with dysregulated adipocyte metabolism and enhanced inflammation. We also demonstrate that SIRT1 is a key regulator of proliferation in preadipocytes. Quantitative proteomics reveal that the c-Myc pathway is altered to drive enhanced proliferation in SIRT1-silenced 3T3-L1 cells. Moreover, c-Myc is hyperacetylated, levels of p27 are reduced, and cyclin-dependent kinase 2 (CDK2) is activated upon SIRT1 reduction. Remarkably, differentiating SIRT1-silenced preadipocytes exhibit enhanced mitotic clonal expansion accompanied by reduced levels of p27 as well as elevated levels of CCAAT/enhancer-binding protein β (C/EBPβ) and c-Myc, which is also hyperacetylated. c-Myc activation and enhanced proliferation phenotype are also found to be SIRT1- dependent in proliferating mouse embryonic fibroblasts and differentiating human SW872 preadipocytes. Reducing both SIRT1 and c-Myc expression in 3T3-L1 cells simultaneously does not induce the adipocyte hyperplasia phenotype, confirming that SIRT1 controls adipocyte hyperplasia through c-Myc regulation. A better understanding of the molecular mechanisms of adipocyte hyperplasia will open new avenues toward understanding obesity. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.


Al-Rasheid N.,University College London | Gray R.,Whittington Hospital | Sufi P.,Whittington Hospital | Marina-Gonzalez N.,University College London | And 4 more authors.
Obesity Surgery | Year: 2014

We determined whether persistent nausea and vomiting (N/V) symptoms following Roux-en-Y gastric bypass surgery is due to elevated systemic glucagon-like peptide-1 (GLP-1) and leptin in female non-diabetic subjects. Subjects with N/V post-Roux-en-Y gastric bypass (RYGB) surgery had significantly elevated fasting GLP-1 levels compared to that with post-operative asymptomatic subjects and to morbidly obese, obese and lean subjects not undergoing surgery. Weight loss, glycaemia, insulin and post-prandial GLP-1 levels were similar in all post-operative subjects. Despite comparable BMI, leptin was significantly lower in symptomatic subjects. Furthermore, leptin secretion from subcutaneous adipose tissue was inhibited by GLP-1 (0.1–1.0 nM; n = 6). Persistent N/V following RYGB surgery is associated with elevated fasting GLP-1, but lower leptin levels. The latter may be a consequence of the direct GLP-1 inhibition of leptin secretion from adipose tissue. © 2014, The Author(s).


Farooq A.,Qatar Orthopaedic and Sports Medicine Hospital | Knez W.L.,Qatar Orthopaedic and Sports Medicine Hospital | Knez K.,Qatar Orthopaedic and Sports Medicine Hospital | Al-Noaimi A.,Supreme Council of Health | And 3 more authors.
Mediators of Inflammation | Year: 2013

Recent studies from the Gulf region suggest that compared to men, women have a greater risk of developing metabolic syndrome (MeS). Objective. To investigate gender differences in body composition, adipokines, inflammatory markers, and aerobic fitness in a cohort of healthy Qatari adults. Participants. Healthy Qatari (n=58) were matched for age, gender, and body mass index. Methods. Body composition and regional fat distribution were determined by dual-energy X-ray absorptiometry and computerized tomography. Laboratory assessments included serum levels of fasting glucose, insulin, lipid profile analysis, adipokines, and inflammatory markers. Subjects were also evaluated for aerobic fitness. Results. Women had more adipose tissue in the total abdominal (P=0.04) and abdominal subcutaneous (P=0.07) regions compared to men. Waist circumference and indices of insulin sensitivity were similar; however, women had a more favourable lipid profile than men. Serum adiponectin and leptin levels were significantly higher in women, whereas inflammatory profiles were not different between men and women. Aerobic fitness was lower in women and was associated with abdominal fat accumulation. Conclusion. In premenopausal women, higher levels of adiponectin may support maintenance of insulin sensitivity and normolipidemia despite greater adiposity. However, poor aerobic fitness combined with abdominal fat accumulation may explain their greater future risk of MeS compared with men. © 2013 Abdulaziz Farooq et al.


- Proposed dividend of EUR 1.05 per share (2015: EUR 0.85 per share) marks an increase of 23.5% - Revenues up 7.2% in financial year 2016 to EUR 1,375.5m - Adjusted EBITDA climbs to EUR 307.8m; at constant exchange rates to EUR 311.3m - Adjusted earnings per share after non-controlling interests increased from EUR 3.41 to EUR 4.22 - Focus on core business: sale of the Life Science Research Division completed as of October 31, 2016 Gerresheimer AG brought financial year 2016 to a successful close and sees strong growth prospects for the years ahead. Gerresheimer is one of the leading partners to the pharma and healthcare industry worldwide and manufactures glass and plastic pharma and cosmetics packaging. "2016 was a successful year for us. We delivered on our guidance for all key performance indicators and have grown substantially. Moreover, we further sharpened our focus on our core business. Going forward, we will continuously expand our development capabilities and product portfolio for the biotech and specialty pharma industry. In addition, we aim to further increase our profitability. The Company is ready for the challenges in the next years ahead," said Uwe Röhrhoff, CEO of Gerresheimer AG. As of October 31, 2016, Gerresheimer sold its Life Science Research Division-the laboratory glassware business. In accordance with International Financial Reporting Standards (IFRS), the division is therefore classified as a discontinued operation. In simple terms, from the time of classification as a discontinued operation, all income and expense items in the consolidated income statement are adjusted for the current year and retrospectively for all comparative periods to be reported upon and are shown in a separate item. Gerresheimer increased revenues in financial year 2016 (December 1, 2015 to November 30, 2016) by 7.2% to EUR 1,375.5m. On an organic basis, revenues went up by 2.9% to EUR 1,383.1m, within the target range of EUR 1,400m plus or minus EUR 25m. Notable revenue growth was generated with inhalers, plastic pharma packaging, injection vials and cosmetic glass. Adjusted EBITDA climbed in financial year 2016 to EUR 307.8m and at constant exchange rates to EUR 311.3m-at the upper end of the guidance range of EUR 305m plus or minus EUR 10m. The adjusted EBITDA margin was for the first time above the 22% mark, at 22.4% compared with a prior-year figure of 20.5%. Net income increased by 49.3% to EUR 168.2m, notably due to the sale of the Life Science Research Division. Adjusted earnings per share after non-controlling interests rose from EUR 3.41 to EUR 4.22. At 15.8% excluding the Life Science Research Division, average net working capital as a percentage of revenues likewise exceeded the Company's expectations. Net financial debt was scaled back by EUR 89.3m to EUR 788.2m, mainly due to the proceeds from the sale of the Life Science Research Division. Leverage, the ratio of net financial debt to adjusted EBITDA, was reduced from 2.9 to 2.6. Gerresheimer's capital expenditure in financial year 2016, at EUR 113.2m compared with EUR 125.8m in the prior year, corresponded to 8.2% of revenues at constant exchange rates excluding the Life Science Research Division. The Company continued to invest in standardizing and modernizing the machinery park in the glass segment. It also modernized the German cosmetic glass plant in Tettau and further expanded decorating capacity. Expansion continued at the Peachtree City plant in the USA, which produces medical plastic systems such as asthma inhalers. "We are optimistic for the future and continue to invest in key growth markets, even though the beginning of financial year 2016/17 appears to be more difficult than the start of the prior year. Our dividend proposal, representing a 23.5% increase to EUR 1.05 per share, reflects the significant improvement in our financial performance indicators," Uwe Röhrhoff added. Gerresheimer's expectations for financial year 2017 are set out in the following, in each case based on constant exchange rates. For the US dollar-which is expected to have the largest currency impact on the Group currency, accounting for about a third of Group revenues in 2017-Gerresheimer has assumed an exchange rate of approximately USD 1.10 to EUR 1.00. In financial year 2017, Gerresheimer anticipates Group revenues of around EUR 1.43bn (plus or minus EUR 25m) on a constant exchange rate basis, compared with EUR 1,375.5m in 2016. Adjusted EBITDA is expected to increase from EUR 308m in 2016 to some EUR 320m (plus or minus EUR 10m) in financial year 2017. Based on the improvement in adjusted EBITDA, adjusted earnings per share after non-controlling interests-the basis of Gerresheimer AG's dividend policy-is projected to rise to a figure in the range EUR 4.20 per share to EUR 4.55 per share (2016 adjusted for the discontinued operation comprising the Life Science Research Division: EUR 4.07 per share). Largely due to the favorable growth prospects and as a result of the initiatives to boost productivity and quality, capital expenditure in the financial year 2017 is expected to amount to around 8% of revenues at constant exchange rates. The Company's expectations through to the end of 2018 are as follows: At the Annual General Meeting on April 26, 2017, the Management Board and Supervisory Board will be jointly proposing that a dividend of EUR 1.05 per share be paid out for financial year 2016. This represents an increase of 23.5% against the prior-year dividend. The dividend ratio amounts to 24.9% of adjusted net income after non-controlling interests. The Annual Report is available here: http://www.gerresheimer.com/en/investor-relations/reports Corss reference: Full press release including table is available at: http://www.presseportal.de/nr/9072/dokument


Diboun I.,Cornell College | Mathew S.,Cornell College | Al-Rayyashi M.,Cornell College | Elrayess M.,Life science research division | And 7 more authors.
BMC Plant Biology | Year: 2015

Background: Dates are tropical fruits with appreciable nutritional value. Previous attempts at global metabolic characterization of the date metabolome were constrained by small sample size and limited geographical sampling. In this study, two independent large cohorts of mature dates exhibiting substantial diversity in origin, varieties and fruit processing conditions were measured by metabolomics techniques in order to identify major determinants of the fruit metabolome. Results: Multivariate analysis revealed a first principal component (PC1) significantly associated with the dates' countries of production. The availability of a smaller dataset featuring immature dates from different development stages served to build a model of the ripening process in dates, which helped reveal a strong ripening signature in PC1. Analysis revealed enrichment in the dry type of dates amongst fruits with early ripening profiles at one end of PC1 as oppose to an overrepresentation of the soft type of dates with late ripening profiles at the other end of PC1. Dry dates are typical to the North African region whilst soft dates are more popular in the Gulf region, which partly explains the observed association between PC1 and geography. Analysis of the loading values, expressing metabolite correlation levels with PC1, revealed enrichment patterns of a comprehensive range of metabolite classes along PC1. Three distinct metabolic phases corresponding to known stages of date ripening were observed: An early phase enriched in regulatory hormones, amines and polyamines, energy production, tannins, sucrose and anti-oxidant activity, a second phase with on-going phenylpropanoid secondary metabolism, gene expression and phospholipid metabolism and a late phase with marked sugar dehydration activity and degradation reactions leading to increased volatile synthesis. Conclusions: These data indicate the importance of date ripening as a main driver of variation in the date metabolome responsible for their diverse nutritional and economical values. The biochemistry of the ripening process in dates is consistent with other fruits but natural dryness may prevent degenerative senescence in dates following ripening. Based on the finding that mature dates present varying extents of ripening, our survey of the date metabolome essentially revealed snapshots of interchanging metabolic states during ripening empowering an in-depth characterization of underlying biology. © 2015 Diboun et al.


Alsaadi K.,Anti Doping Laboratory Qatar | Voss S.C.,Anti Doping Laboratory Qatar | Kraiem S.,Anti Doping Laboratory Qatar | Alwahaibi A.,Anti Doping Laboratory Qatar | And 9 more authors.
Drug Testing and Analysis | Year: 2015

This study investigated the effect of Ramadan on the haematological and steroid module of the Athletes Biological Passport (ABP) of the World Anti-Doping Agency (WADA). Nine healthy physically active subjects were tested in the morning and afternoon for two days before and three days during Ramadan. Sample collection and all analyses were performed according to WADA technical documents. Although there were significant changes in the haemoglobin concentration during Ramadan, especially during the first fasting week, none of the subjects in this study exceeded the individually calculated thresholds of the ABP. No significant effects on testosterone/epitestosterone (T/E) ratio were observed but only the afternoon specific gravity (SG) of the urine was elevated. Thus, when urinary steroid concentrations are required, SG corrections need to be performed. The haematological and the steroid module of the ABP can be reliably applied during Ramadan as the observed changes are only marginal. © 2015 John Wiley & Sons, Ltd.


PubMed | Anti Doping Laboratory Qatar, Life Science Research Division and Qatar University
Type: Journal Article | Journal: Drug testing and analysis | Year: 2015

This study investigated the effect of Ramadan on the haematological and steroid module of the Athletes Biological Passport (ABP) of the World Anti-Doping Agency (WADA). Nine healthy physically active subjects were tested in the morning and afternoon for two days before and three days during Ramadan. Sample collection and all analyses were performed according to WADA technical documents. Although there were significant changes in the haemoglobin concentration during Ramadan, especially during the first fasting week, none of the subjects in this study exceeded the individually calculated thresholds of the ABP. No significant effects on testosterone/epitestosterone (T/E) ratio were observed but only the afternoon specific gravity (SG) of the urine was elevated. Thus, when urinary steroid concentrations are required, SG corrections need to be performed. The haematological and the steroid module of the ABP can be reliably applied during Ramadan as the observed changes are only marginal.


PubMed | Life science Research Division
Type: Journal Article | Journal: Current vascular pharmacology | Year: 2016

Adipose tissue (AT) is now widely accepted as a key secretary organ, as well as an energy storage depot. It secretes a series of cytokines, hormones and bioactive molecules: adipokines. Adiponectin is an abundant systemic adipokine that uniquely is reduced in obesity and increases on weight loss, is anti-inflammatory, promotes insulin sensitivity and affords cardiometabolic protection. It was considered a true adipokine, in that it is exclusively generated by the adipocytes of the adipose tissue. However, recent evidence points to it being secreted by a range of other organs. This review summarizes the non-adipose sources of adiponectin especially that derived from the endothelium, its vasoprotective role and intracellular signalling pathways. Endothelium derived adiponectin may potentially be a new target for clinical intervention in cardiovascular disease.

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