All Publications

  • Change in practice of RRSO consults and procedures during the COVID-19 pandemic O'Mara, A., Kurian, A., Benedict, C., Diver, E. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2022: S275
  • Risk-reducing salpingo-oophorectomy consults and practices during the COVID-19 pandemic Gynecologic Oncology Reports O'Mara, A. E., Benedict, C., Kurian, A. W., Wagner, S. K., Diver, E. J. 2022
  • Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity JOURNAL OF CLINICAL INVESTIGATION O'Mara, A. E., Johnson, J. W., Linderman, J. D., Brychta, R. J., McGehee, S., Fletcher, L. A., Fink, Y. A., Kapuria, D., Cassimatis, T. M., Kelsey, N., Cero, C., Sater, Z., Piccinini, F., Baskin, A. S., Leitner, B. P., Cai, H., Millo, C. M., Dieckmann, W., Walter, M., Javitt, N. B., Rotman, Y., Walter, P. J., Ader, M., Bergman, R. N., Herscovitch, P., Chen, K. Y., Cypess, A. M. 2020; 130 (5): 2209-2219


    BACKGROUNDMirabegron is a β3-adrenergic receptor (β3-AR) agonist approved only for the treatment of overactive bladder. Encouraging preclinical results suggest that β3-AR agonists could also improve obesity-related metabolic disease by increasing brown adipose tissue (BAT) thermogenesis, white adipose tissue (WAT) lipolysis, and insulin sensitivity.METHODSWe treated 14 healthy women of diverse ethnicities (27.5 ± 1.1 years of age, BMI of 25.4 ± 1.2 kg/m2) with 100 mg mirabegron (Myrbetriq extended-release tablet, Astellas Pharma) for 4 weeks in an open-label study. The primary endpoint was the change in BAT metabolic activity as measured by [18F]-2-fluoro-d-2-deoxy-d-glucose (18F-FDG) PET/CT. Secondary endpoints included resting energy expenditure (REE), plasma metabolites, and glucose and insulin metabolism as assessed by a frequently sampled intravenous glucose tolerance test.RESULTSChronic mirabegron therapy increased BAT metabolic activity. Whole-body REE was higher, without changes in body weight or composition. Additionally, there were elevations in plasma levels of the beneficial lipoprotein biomarkers HDL and ApoA1, as well as total bile acids. Adiponectin, a WAT-derived hormone that has antidiabetic and antiinflammatory capabilities, increased with acute treatment and was 35% higher upon completion of the study. Finally, an intravenous glucose tolerance test revealed higher insulin sensitivity, glucose effectiveness, and insulin secretion.CONCLUSIONThese findings indicate that human BAT metabolic activity can be increased after chronic pharmacological stimulation with mirabegron and support the investigation of β3-AR agonists as a treatment for metabolic disease.TRIAL NCT03049462.FUNDINGThis work was supported by grants from the Intramural Research Program of the NIDDK, NIH (DK075112, DK075116, DK071013, and DK071014).

    View details for DOI 10.1172/JCI131126

    View details for Web of Science ID 000571121100015

    View details for PubMedID 31961826

    View details for PubMedCentralID PMC7190915

  • Pheochromocytoma and Paraganglioma Patients With Poor Survival Often Show Brown Adipose Tissue Activation JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Sater, Z., Jha, A., Hamimi, A., Mandl, A., Hartley, I. R., Gubbi, S., Patel, M., Gonzales, M., Taieb, D., Civelek, A., Gharib, A. M., Auh, S., O'Mara, A. E., Pacak, K., Cypess, A. M. 2020; 105 (4): 1176-85


    Pheochromocytomas/paragangliomas (PPGLs) are neuroendocrine tumors that can secrete norepinephrine (NE). Brown adipose tissue (BAT) activation is mediated through the action of NE on β-adrenoceptors (β-ARs). In some malignancies, BAT activation is associated with higher cancer activity.To study the relationship between BAT activation and PPGL clinical outcomes.A retrospective case-control study that included 342 patients with PPGLs who underwent 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (18F-FDG PET/CT) imaging at the National Institutes of Health (NIH). We excluded all patients with parasympathetic tumors and those who underwent 18F-FDG PET/CT after PPGL resection. Scans of 205 patients were reviewed by 2 blinded nuclear medicine physicians; 16 patients had BAT activation on 18F-FDG PET/CT [7.80%; age 27.50 (15.00-45.50) years; 10 female/6 male; body mass index [BMI] 24.90 [19.60-25.35] kg/m2). From the remaining 189 patients, we selected 36 matched controls (age 34.4 [25.4-45.5] years; 21 female/15 male; BMI 25.0 [22.0-26.0] kg/m2).Overall survival.The presence of active BAT on 18F-FDG PET/CT was associated with decreased overall survival when compared with the control group (HRz 5.80; 95% CI, 1.05-32.05; P = 0.02). This association remained significant after adjusting for the SDHB mutation. Median plasma NE in the BAT group was higher than the control group [4.65 vs 0.55 times above the upper limit of normal; P < 0.01]. There was a significant association between higher plasma NE levels and mortality in PPGLs in both groups.Our findings suggest that the detection of BAT activity in PPGL patients is associated with higher mortality. We suggest that BAT activation could either be reflecting or contributing to a state of increased host stress that may predict poor outcome in metastatic PPGL.

    View details for DOI 10.1210/clinem/dgz314

    View details for Web of Science ID 000525950100134

    View details for PubMedID 31903484

    View details for PubMedCentralID PMC7059996

  • Sexual Dimorphisms in Adult Human Brown Adipose Tissue OBESITY Fletcher, L. A., Kim, K., Leitner, B. P., Cassimatis, T. M., O'Mara, A. E., Johnson, J. W., Halprin, M. S., McGehee, S. M., Brychta, R. J., Cypess, A. M., Chen, K. Y. 2020; 28 (2): 241-246


    This study aimed to quantify and compare the amount, activity, and anatomical distribution of cold-activated brown adipose tissue (BAT) in healthy, young, lean women and men.BAT volume and 18 F-fluorodeoxyglucose uptake were measured by positron emission tomography and computerized tomography in 12 women and 12 men (BMI 18.5-25 kg/m2 , aged 18-35 years) after 5 hours of exposure to their coldest temperature before overt shivering.Women had a lower detectable BAT volume than men (P = 0.03), but there was no difference after normalizing to body size. The mean BAT glucose uptake and relative distribution of BAT did not differ by sex. 18 F-fluorodeoxyglucose uptake consistent with BAT was observed in superficial dorsocervical adipose tissue of 6 of 12 women but only 1 of 12 men (P = 0.02). This potential BAT depot would pose fewer biopsy risks than other depots.Despite differences in adiposity and total BAT volume, we found that healthy, lean, young women and men do not differ in the relative amount, glucose uptake, and distribution of BAT. Dorsocervical 18 F-fluorodeoxyglucose uptake was more prevalent in women and may be a remnant of interscapular BAT seen in human newborns. Future studies are needed to discern how BAT contributes to whole-body thermal physiology and body weight regulation in women and men.

    View details for DOI 10.1002/oby.22698

    View details for Web of Science ID 000508645300007

    View details for PubMedID 31970907

    View details for PubMedCentralID PMC6986330

  • The Selective Human Beta 3 Adrenergic Receptor Mirabegron Potently Activates Lipolysis in Human White Adipocytes Cero, C., Johnson, J. W., O'Mara, A., Linderman, J. D., Cypess, A. M. AMER DIABETES ASSOC. 2019
  • Whole Body and Regional Quantification of Active Human Brown Adipose Tissue Using F-18-FDG PET/CT JOVE-JOURNAL OF VISUALIZED EXPERIMENTS Kim, K., Huang, S., Fletcher, L. A., O'Mara, A. E., Tal, I., Brychta, R. J., Cypess, A. M., Chen, K. Y., Leitner, B. P. 2019


    In endothermic animals, brown adipose tissue (BAT) is activated to produce heat for defending body temperature in response to cold. BAT's ability to expend energy has made it a potential target for novel therapies to ameliorate obesity and associated metabolic disorders in humans. Though this tissue has been well studied in small animals, BAT's thermogenic capacity in humans remains largely unknown due to the difficulties of measuring its volume, activity, and distribution. Identifying and quantifying active human BAT is commonly performed using 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography and computed tomography (PET/CT) scans following cold-exposure or pharmacological activation. Here we describe a detailed image-analysis approach to quantify total-body human BAT from 18F-FDG PET/CT scans using an open-source software. We demonstrate the drawing of user-specified regions of interest to identify metabolically active adipose tissue while avoiding common non-BAT tissues, to measure BAT volume and activity, and to further characterize its anatomical distribution. Although this rigorous approach is time-consuming, we believe it will ultimately provide a foundation to develop future automated BAT quantification algorithms.

    View details for DOI 10.3791/58469

    View details for Web of Science ID 000466500600012

    View details for PubMedID 30985755

  • Stimulation of the beta(3)-Adrenergic Receptor via Mirabegron Induces Lipolysis and Thermogenesis in Human Adipocytes Cero, C., O'Mara, A., Johnson, J. W., Baskin, A. S., Linderman, J. D., Cypess, A. AMER DIABETES ASSOC. 2018
  • Physiological Responses to Daily Use of Beta-Three Adrenergic Receptor Agonist, Mirabegron O'Mara, A., Cypess, A., Cero, C., Johnson, J. W., Linderman, J. D., Leitner, B., Fletcher, L., Brychta, R., Kapuria, D., Mcgehee, S., Rotman, Y. AMER DIABETES ASSOC. 2018
  • Functional and Developmental Heterogeneity in Human Adipose Tissue Depots Johnson, J. W., Cero, C., O'Mara, A., Linderman, J. D., Baskin, A. S., Cypess, A. AMER DIABETES ASSOC. 2018