Browsing by Author "Ory, Daniel S."

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    Bariatric Surgery–Induced Cardiac and Lipidomic Changes in Obesity‐Related Heart Failure with Preserved Ejection Fraction
    (Wiley, 2018) Mikhalkova, Deana; Holman, Sujata R.; Jiang, Hui; Sagir, Mohammed; Novak, Eric; Coggan, Andrew R.; O'Connor, Robert; Bashir, Adil; Jamal, Ali; Ory, Daniel S.; Schaffer, Jean E.; Eagon, J. Christopher; Peterson, Linda R.; Kinesiology, School of Physical Education and Tourism Management
    Objective To determine the effects of gastric bypass on myocardial lipid deposition and function and the plasma lipidome in women with obesity and heart failure with preserved ejection fraction (HFpEF). Methods A primary cohort (N = 12) with HFpEF and obesity underwent echocardiography and magnetic resonance spectroscopy both before and 3 months and 6 months after bariatric surgery. Plasma lipidomic analysis was performed before surgery and 3 months after surgery in the primary cohort and were confirmed in a validation cohort (N = 22). Results After surgery‐induced weight loss, Minnesota Living with Heart Failure questionnaire scores, cardiac mass, and liver fat decreased (P < 0.02, P < 0.001, and P = 0.007, respectively); echo‐derived e′ increased (P = 0.03), but cardiac fat was unchanged. Although weight loss was associated with decreases in many plasma ceramide and sphingolipid species, plasma lipid and cardiac function changes did not correlate. Conclusions Surgery‐induced weight loss in women with HFpEF and obesity was associated with improved symptoms, reverse cardiac remodeling, and improved relaxation. Although weight loss was associated with plasma sphingolipidome changes, cardiac function improvement was not associated with lipidomic or myocardial triglyceride changes. The results of this study suggest that gastric bypass ameliorates obesity‐related HFpEF and that cardiac fat deposition and lipidomic changes may not be critical to its pathogenesis.
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    Whole exome sequencing and functional characterization increase diagnostic yield in siblings with a 46, XY difference of sexual development (DSD)
    (Elsevier, 2021) Luna, Sofia E.; Wegner, Daniel J.; Gale, Sarah; Yang, Ping; Hollander, Abby; St. Dennis-Feezle, Lori; Nabhan, Zeina M.; Ory, Daniel S.; Cole, F. Sessions; Wambach, Jennifer A.; Pediatrics, School of Medicine
    Pathogenic biallelic variants in HSD17B3 result in 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3) deficiency, variable disruption of testosterone production, and phenotypic diversity among 46, XY individuals with differences of sexual development (DSDs). We performed quad whole exome sequencing (WES) on two male siblings with microphallus, perineal hypospadias, and bifid scrotum and their unaffected parents. Both male siblings were compound heterozygous for a rare pathogenic HSD17B3 variant (c.239 G > A, p.R80Q) previously identified among individuals with 17β-HSD3 deficiency and a HSD17B3 variant (c.641A > G, p.E214 G) of uncertain significance. Following WES, the siblings underwent hCG stimulation testing with measurement of testosterone, androstenedione, and dihydrotestosterone which was non-diagnostic. To confirm pathogenicity of the HSD17B3 variants, we performed transient transfection of HEK-293 cells and measured conversion of radiolabeled androstenedione to testosterone. Both HSD17B3 variants decreased conversion of radiolabeled androstenedione to testosterone. As pathogenic HSD17B3 variants are rare causes of 46, XY DSD and hCG stimulation testing may not be diagnostic for 17β-HSD3 deficiency, WES in 46, XY individuals with DSDs can increase diagnostic yield and identify genomic variants for functional characterization of disruption of testosterone production.