A metabolic dependency of EBV can be targeted to hinder B cell transformation.

After infection of B cells, Epstein-Barr virus (EBV) engages host pathways that mediate cell proliferation and transformation, contributing to the propensity of the virus to drive immune dysregulation and lymphomagenesis. We found that the EBV protein EBNA2 initiates nicotinamide adenine dinucleotide (NAD) de novo biosynthesis by driving expression of the metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1) in infected B cells. Virus-enforced NAD production sustained mitochondrial complex I activity, to match adenosine triphosphate (ATP) production with bioenergetic requirements of proliferation and transformation. In transplant patients, IDO1 expression in EBV-infected B cells, and a serum signature of increased IDO1 activity, preceded development of lymphoma. In humanized mice infected with EBV, IDO1 inhibition reduced both viremia and lymphomagenesis. Virus-orchestrated NAD biosynthesis is therefore a druggable metabolic vulnerability of EBV-driven B cell transformation, opening therapeutic possibilities for EBV-related diseases.

Factors Associated With Weight Loss After Laparoscopic Adjustable Gastric Banding in Adolescents With Severe Obesity.

Childhood obesity is associated with many comorbidities. Bariatric surgery is known to be efficient for reducing weight in adolescents. Objectives: The primary outcome was to identify somatic or psychosocial factors associated with success at 24 months after a laparoscopic adjustable gastric banding (LAGB) procedure in our cohort of adolescents with severe obesity. Secondary endpoints were to describe weight loss outcomes, comorbidity resolution, and complications. Methods: We have retrospectively reviewed medical records of patients who had LAGB placed between 2007 and 2017. Factors associated with success at 24 months after LAGB were researched, with success being defined as positive percentage of excess weight loss (%EWL) at 24 months. Results: Forty-two adolescents underwent a LAGB procedure, the mean %EWL was 34.1% at 24 months, with improvement in most comorbidities and without major complications. Having lost weight before surgery was associated with success, whereas a high body mass index at surgery was associated with a higher risk of failure. No other factor was found to be associated with success. Conclusion: Comorbidities mostly improved 24 months after LAGB and no major complication occurred. Having lost weight before surgery was associated with a successful surgery, whereas a high body mass index at surgery increases the risk of failure.

Lower Circulating Sertoli and Leydig Cell Hormone Levels During Puberty in Obese Boys: A Cross-sectional Study.

CONTEXT: Alterations in semen characteristics and circulating Sertoli and Leydig cell hormones have been described in obese male adults. Whether hormonal alterations occur before adulthood has not been fully evaluated. OBJECTIVE: We describe circulating Sertoli and Leydig cell hormone levels in overweight-obese (ow/ob) boys through childhood and adolescence in a cross-sectional study. METHODS: Monocentric study in the Pediatric Endocrinology Unit of Angers University Hospital. Three hundred and fifty-one obese and overweight boys aged 5-19 years underwent physical examination, dual-energy X-ray absorptiometry for body composition, oral glucose tolerance test on insulin and glucose, and measurements of follicle-stimulating hormone, luteinizing hormone, anti-Müllerian hormone (AMH), inhibin B, testosterone, and estradiol. Hormonal levels were compared with normative data obtained from 652 healthy nonoverweight nonobese boys of similar age or Tanner stage. RESULTS: Median inhibin B and testosterone levels during puberty were significantly lower in ow/ob than in healthy boys (1) from age >12 years and thereafter for inhibin B, and (2) from age >14 years and thereafter for testosterone. At Tanner stages 4 and 5, 26%, 31%, and 18% of inhibin B, testosterone, and AMH values were below the 5th percentile in ow/ob subjects (P < .01). In multiple regression analyses, estradiol and total bone mineral density Z-score were negative predictors of inhibin B, fat mass percentage was a negative predictor of testosterone, and insulin was a negative predictor of AMH. CONCLUSION: Lower Sertoli and Leydig cell hormone levels during puberty were observed in the ow/ob boys.