bluuebunny/crossref_metadata_2025_split huggingface dataset:
OR23-3 Hunger Hormone Asprosin Activates Orexigenic Neurons via SK Currents
Authors: Feng Bing , Greenway Frank , Harms Jerney , Liu Hesong , Wang Chunmei , Xu Pingwen , He Yanlin 
Published: November 2022

Abstract
Neurons that co-express the orexigenic agouti-related protein (AgRP) and neuropeptide Y (NPY) are indispensable for normal feeding behavior. Firing activities of AgRP/NPY neurons dynamically fluctuate with energy status and coordinate appropriate feeding behavior to meet nutritional demands. We previously demonstrated that asprosin, a recently discovered fasting-induced glucogenic and orexigenic hormone, crosses the blood-brain barrier and directly activates the orexigenic AgRP/NPY neurons via a cyclic cAMP-dependent pathway. However, intrinsic mechanisms on how asprosin regulates AgRP/NPY neural activities during the fed-to-fasted transition are not fully understood. In the satiated mice with low circulating levels of asprosin, we found that AgRP/NPY neurons expressed high levels of the small conductance calcium-activated potassium channel 3 (SK3) and were inhibited by SK3-mediated potassium currents. Conversely, in 24 hour-fasting mice with high levels of asprosin, AgRP/NPY neurons expressed low levels of SK3 and were activated via inhibition of SK3-mediated potassium currents. Notably, the stimulatory effects of asprosin on AgRP/NPY neurons were blunted in mice with SK3 selectively deleted in the AgRP/NPY neurons, further supporting a mediating role of SK3.
Moreover, we also identified protein tyrosine phosphatase receptor δ (Ptprd), a membrane-bound phosphatase receptor, as the orexigenic asprosin-receptor. Deletion of Ptprd in AgRP/NPY neurons abolished asprosin's stimulatory effect on SK3-mediated currents and protected mice from diet-induced obesity.
Lastly, increased circulating levels of asprosin promoted hyperphagia, body weight gain, and glucose intolerance. On the other hand, anti-asprosin antibody treatment decreased food intake and body weight by inhibiting AgRP/NPY and other orexigenic hypothalamic neurons via SK currents stimulation.
In summary, our data support a model that asprosin acts on Ptprd expressed by AgRP/NPY neurons to inhibit SK3 current, further activating AgRP/NPY neurons to increase food intake and body weight. Our findings also provided preclinical evidence that asprosin-neutralizing antibodies could be used to treat obesity.
Presentation: Monday, June 13, 2022 11:45 a.m. - 12:00 p.m.
PSUN113 Evaluating The Efficacy Of Anti-Obesity Medications In a Multidisciplinary Weight Management Clinic At a VA Medical Center
Authors: Goettemoeller Travis , Mazhar Hiba , Chippior Jessica , Rajpal Aman 
Published: November 2022

Abstract

Objective
Anti-obesity medications have been shown to be effective in multiple randomized clinical trials, but there is limited data on the efficacy of these medications in the veteran population. This study was aimed to evaluate the effectiveness of anti-obesity medications in a multidisciplinary weight management clinic at our VA medical center.

Methods
This was a retrospective, descriptive study of 98 patients seen in a multidisciplinary weight management clinic at our VA medical center between January 1, 2019 and October 31, 2021. General requirements to be seen in the clinic were a BMI &gt;30 or BMI &gt;27 with comorbid conditions. Patients seen at least twice in the clinic were included in the study. Patients who received anti-obesity medications (phentermine-topiramate, naltrexone-bupropion, or GLP-1 receptor agonist (liraglutide or semaglutide)) had weights recorded at medication start date and at 2-4 months, 4-8 months, 8-10 months, and 10-14 months intervals. Baseline BMI, HbA1c, LDL-C and triglycerides were recorded at the medication start and followed up at similar intervals.

Results
There were 98 participants (56% males) within this study, with mean age of 54.9 years, mean baseline weight of 127.3 kg, and BMI of 43.5. Of all 98 patients seen in the clinic (regardless of being on anti-obesity medicine), 85 experienced some weight loss with 39 losing at least 5% of their body weight. The average weight loss from first to last visit was 4.1%. There were 72 patients who received anti-obesity medications for at least 3 consecutive months, including 12 patients who were subsequently trialed on a second class of anti-obesity medication. There were 35 trials of Qsymia, 43 trials of GLP-1 receptor agonists, and 6 trials of naltrexone-bupropion. For those patients receiving medications, average weight loss at 2-4 months was 3.7% (N=73), 4-8 months was 4.9% (N=58), 8-10 months was 6.0% (N=32), and 10-14 months was 5.5% (N=29). The percentage of patients able to lose at least 5.0% of their weight was 30.1% at 2-4 months, 43.1% at 4-8 months, 68.8% at 8-10 months, and 51.7% at 10-14 months. There was a decrease noted in HbA1c and LDL-C at all time periods, while there was no change in triglycerides.

Conclusion
Our data shows the effectiveness of anti-obesity medications in a veteran population seen in a multidisciplinary weight management clinic, though to a lesser extent as compared to clinical trials. Given the higher prevalence of multiple chronic conditions seen in veterans when compared to the general population, these patients have additional challenges when trying to achieve their weight loss goals. Further study must be performed to determine the long-term effectiveness and tolerability of these medications in this population. The differential effects among the anti-obesity medications should also be investigated further.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN121 Nonalcoholic Steatohepatitis (NASH), Race/Ethnicity, and Gender in Adult US Population of NHANES 17-18
Authors: Friedman Theodore , Shaheen Magda , Schrode Katrina , Kermah Dulcie , Zarrinpar Ali , Puri Vishwajeet , Najjar Sonia 
Published: November 2022

Abstract
Nonalcoholic steatohepatitis (NASH) is a more severe form of non-alcoholic liver disease (NAFLD) that is characterized by inflammation and liver damage. Previous studies have identified a strong association between NAFLD and race/ethnicity, but there has been less investigation of a racial disparity specifically in NASH. We tested the association between NASH and race/ethnicity in the adult US population of NHANES 17-18 (n=5492). Hepatic steatosis (HS) was diagnosed by FibroScan® using controlled attenuation parameter (CAP) values (stages): S0 &lt;238, S1 (mild)=238-259, S2 (moderate)=260-290, S3 (severe) &gt;290. Participants with moderate/severe steatosis without the exclusion criteria (elevated transferrin level &gt;50%, chronic hepatitis B, chronic hepatitis C, excessive alcohol use, or prescription medications that might cause HS) were considered to have NAFLD (n=3,292). Subjects with NAFLD and a HAIR score (defined by HOMA-IR, hypertension, and ALT) of ≥ 2 were considered to have NASH, as opposed to simple NAFLD. Data were analyzed using Chi square and multinomial regression adjusting for the other independent variables [demographics: (age, gender, education, poverty), physical activity, smoking, waist-hip ratio, body mass index, triglyceride, cholesterol, glucose, HbA1c, C-reactive protein (hsCRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and healthy eating index (HEI)] using SAS (Release V.9.1.3, 2002; SAS) and including sample weights and design. The overall prevalence of NASH was 7.6% and it varied by race/ethnicity. Mexican Americans had the highest prevalence (10.6%), followed by other Hispanics (9.1%); Non-Hispanic Whites had the lowest prevalence (6.8%) (p&lt;0.05). Females had lower prevalence (4.8%) than males (10.4%) (p&lt;0.05). Among males, Mexican Americans had the highest prevalence (14.3%), followed by Blacks (11.3%), and other race had the lowest prevalence (7.7%). In the overall adjusted model, Blacks had lower odds of NASH relative to Non-Hispanic Whites [Adjusted Odds Ratio (AOR)=0.4, 95% confidence interval (CI)=0.3-0.6, p&lt;0.05)]. Although Mexican Americans had higher odds of NASH relative to Non-Hispanic Whites, it was not statistically significant (AOR=1.9, 95%CI=0.9-3.9, p=0.09). Among males and females, there was no statistical association between NASH and race/ethnicity (p&gt;0.05). We concluded that the prevalence of NASH was highest among Mexican American males relative to the other groups. Targeted interventions for Mexican American males are needed to increase awareness, management and prevention related to NASH.
Grants: R01MD012579, R24DA017298, U54MD007598, S21MD000103, UL1TR001881
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
RF36 | PSUN79 Prolonged Stimulation of β-Adrenergic Receptors in Human Brown and White Adipocytes Increases and then Decreases Metabolic Activity
Authors: Katz Jacqueline M , Pierce Anne E , Zhu Alexander R , Cero Cheryl , Cypess Aaron M 
Published: November 2022

Abstract

Background
Obesity results from excess adipose triglyceride storage and leads to multiple life-threatening complications that may be amenable to novel pharmacological therapies. Both human white and brown adipocytes express β1-, β2-, and β3-adrenergic receptors (β-AR's), and stimulation of each activates converging signaling pathways that regulate essential metabolic and cellular functions. Clinical data indicate that acute and chronic stimulation of the β3-AR with the selective agonist mirabegron increases lipolysis and thermogenesis, thereby making β3-AR activation a promising target to improve obesity-related metabolic disease.

Purpose
In this study, we evaluated in vitro the short-term and prolonged activation of β3-ARs via mirabegron and compared the effects to the activation of β1- and β2-AR.

Methods
Functional cellular assays such as lipolysis and cellular respiration, were measured in immortalized human white (hWA) and brown (hBA) adipocytes derived from the superficial and deep neck depots, respectively. Cells were treated for 6 h (short-term) and 24 h (prolonged) with mirabegron (β3-AR agonist), dobutamine (β1-AR agonist), terbutaline (β2-AR agonist) and isoproterenol (non-selective β-AR agonist). One-way ANOVA was used for statistical analysis.

Findings
In hWA, only short-term activation of the β2-AR induced lipolysis (1.8-fold increase, P=0.0002), while in hBA, both the β2-AR (1.5-fold increase, P=0.04) and β3-AR (1.6 fold increase, P=0.002) increased lipolysis with 6h treatment, as compared to the vehicle. By 24h, lipolysis was blunted in both cell types, likely due to agonist-induced desensitization and downregulation. Distinct from the lipolytic effects ofβ-AR activation, the basal oxygen consumption rate (OCR) was not significantly different among hBA and hWA treated acutely and chronically with each of the three selective β-ARs and positive control isoproterenol. However, in hBA only, prolonged activation of all three β-AR's lowered maximal mitochondrial respiration (isoproterenol: 25% decrease, P=0.0004; dobutamine: 25% decrease, P=0.0003; terbutaline: 26% decrease, P=0.0004; mirabegron: 38% decrease, P&lt;0.0001, respectively). No significant changes in OCR parameters were detected in hWA.

Conclusion
In hBA, acute stimulation of either the β2-AR or β3-AR induces lipolysis. Prolonged exposure to β-agonists comparably lowers maximal cellular respiration, suggesting that all β-AR's are subject to agonist-induced desensitization. Moreover, continuous activation of lipolysis may deplete the intracellular fatty acid pool necessary for mitochondrial oxidative respiration. These responses will need to be addressed before novel adrenergic activators can be utilized to reduce triglyceride stores and treat obesity-related metabolic disease.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:00 p.m. - 1:05 p.m.
PSAT038 A Case of Spontaneous Atraumatic Unilateral Adrenal Hemorrhage
Authors: Bilbatua Martha , Amori Renee 
Published: November 2022

Abstract

Background
Adrenal hemorrhage is a rare disorder with an incidence of 0.1 to 1% for which a cause is identified in most cases. It is usually classified as traumatic or atraumatic, unilateral or bilateral and can result in serious consequences such as adrenal crisis and death if not diagnosed and treated properly. We describe a patient with an atraumatic unilateral adrenal hemorrhage without a known coagulopathy Case presentation: A 51-year-old man with history of COPD and Reynaud's phenomenon presented to the hospital for severe right upper quadrant pain. CT of the abdomen demonstrated a right adrenal hemorrhage of 5.2×4.0×2.6 cm in size, for which Endocrinology was consulted. The patient denied recent trauma or anticoagulation use. Physical examination exhibited generalized abdominal tenderness, without hypotension, or symptoms of acute adrenal insufficiency. Biochemical evaluation showed an AM Cortisol level of 14.3 ug/dL (4.2 - 22.4 ug/dL) and ACTH 67.1 pg/mL (7.2 - 63.3 pg/mL). MRI abdomen showed a decrease in size of the hemorrhage measuring 3.1×1.7×5.2 cm. He was referred to Hematology/Oncology to evaluate for coagulopathy which was unrevealing. About one month from hospital discharge, the patient reported voice hoarseness and was diagnosed with moderately differentiated keratinizing squamous cell carcinoma of larynx. Ten months later PET-CT scan showed hypermetabolic laryngeal mass with bilateral cervical lymphadenopathy without evidence of adrenal gland metastasis with resolution of adrenal hemorrhage, indicative that the hemorrhagic episode is unrelated to this newly diagnosed malignancy.

Discussion
Adrenal hemorrhage is a rare disorder that overall is associated with a 10-20% mortality rate, it is usually classified as traumatic and no traumatic. Most times it is caused by secondary disorders such as trauma, surgery, anticoagulants, infections, but in rare instances is idiopathic. Clinical manifestations of adrenal hemorrhages vary depending on extension of the hemorrhage and early diagnosis is crucial for better outcomes. As per current guidelines, assessment for adrenal insufficiency including hemodynamics, biochemical evaluation and imaging is paramount. To date, clear etiology of primary adrenal hemorrhage is lacking. This case demonstrated an unusual presentation of idiopathic unilateral adrenal hemorrhage without evidence of adrenal insufficiency.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
RF21 | PSAT78 The beta3-Adrenergic Receptor as a Target for the Prevention of Glucocorticoid-induced Adipose Tissue Dysfunction in Rodents
Authors: Gado Manuel , Heinrich Annett , Wiedersich Denise , Bornstein Stefan R , Rauner Martina , Hofbauer Lorenz C , Henneicke Holger 
Published: November 2022

Abstract
Glucocorticoids (GC) are an integral part of anti-inflammatory therapy. However, their therapeutic effectiveness is limited by their deleterious adverse effects such as the development of obesity, diabetes, and cardiometabolic disease. GC-induced obesity arises from excessive fat accumulation in white adipose tissue (WAT) as well as suppressed thermogenic function of brown adipose tissue (BAT). The sympathetic nervous system (SNS) plays a key role in the regulation of both WAT as well as BAT biology. As part of this project, we investigate the interaction between SNS and GC signaling in the adipose organ.
To that end, we modulated the SNS activity in adipose tissues of mice by altering the housing temperature of corticosterone-treated mice and respective controls to either 29°C, 22°C, or 13°C. Following the four-week treatment course, GC-treated mice housed at 29°C and 22°C gained more weight and accumulated more visceral and subcutaneous white fat than their temperature-matched controls. Interestingly, maintaining mice in the 13°C environment protected animals from GC-induced weight gain and obesity. Additionally, cold adaptation effectively prevented the development of GC-driven hyperglycemia, hyperinsulinemia and hyperleptinemia, all of which were readily observed at 29°C and 22°C. Furthermore, the sympathetic innervation as well as the thermogenic capacity of BAT were preserved in cold-acclimated mice in spite of corticosterone treatment, whereas mice housed at higher temperatures showed marked suppression of the thermogenic function in BAT following GC exposure. To further test whether sympathetic activation is responsible for the prevention of GC-induced dysmetabolism by prolonged adaption to cold, we investigated the effect of a pharmacological β3-AR agonist, CL316,243 during GC excess. Similar to cold exposure, selective activation of the β3-AR not only averted the development of GC-induced fat accumulation and hyperinsulinemia, but also preserved the thermogenic capacity in BAT despite exposure to supra-physiological levels of corticosterone.
Taken together, our data indicate that both cold-acclimation as well as β3-AR activation counteract GC-induced obesity, adipose tissues dysfunction, and related metabolic comorbidities. Thus, targeting the β3-AR may represent a potential therapeutic approach to alleviate GC-induced metabolic abnormalities.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 12:42 p.m. - 12:47 p.m.
LBODP022 A Rare Case Of Hypercalcemia: Mycobacterium Avium Complex Induced Hypercalcemia
Authors: Aluko Oluwatomisin A , Akinbamijo Kasopefoluwa , Malmberg Ifeoluwa , SYEED M E H M O O D A , Rather Manzoor 
Published: November 2022

Abstract

Background
Primary hyperparathyroidism and malignancy accounts for 90% of cases of hypercalcemia. Other causes of hypercalcemia are granulomatous diseases of which tuberculosis and sarcoidosis account for most. We report on a patient with acquired immunodeficiency syndrome (AIDS) presenting with new-onset hypercalcemia secondary to mycobacterium avium complex (MAC) infection.

Clinical Case
A 36-year-old man diagnosed with HIV-1/AIDS on ART presented to the hospital 3 months after initial diagnosis with worsening abdominal pain, nausea and vomiting, cough, weight loss and night sweats. He had presented to an outside facility with similar complaints, he had EGD done, was started on Augmentin and Azithromycin, and was awaiting biopsy results. On arrival he was afebrile and without palpable lymphadenopathy. He was found to have a high serum calcium (12.4 mg/dL, n 8.6-10.2 mg/dL) and acute kidney injury (AKI) (creatinine 1.7 mg/dL, n 0.6-1.3 mg/dL). His CD4 count had increased from 17 at time of diagnosis to 80 cells/μL (n 443-1,471 cells/μL). Workup for hypercalcemia revealed an elevated phosphorus (5.2 mg/dL, n 2.5-5. 0 mg/dL), low PTH (&lt;1 pg/mL, n 12-88 pg/mL), elevated 1,25 Vit D level (112 pg/ml, n 20- 79 pg/ml), low PTHrP (8 pg/ml, n 14-27 pg/ml). TSH was mildly elevated (8 uIU/ml, n 0.35-5.50 uIU/ml) with normal free T4 levels. CT scan done on admission revealed bulky retroperitoneal and mesenteric root adenopathy with hepatosplenomegaly initially concerning for lymphoma. Patient was started on intravenous hydration and bisphosphonate was administered. He underwent laparoscopic lymph node biopsy and bronchoscopy with pathology report showing numerous acid-fast organisms, negative for malignancy. AFB culture was positive for MAC. Prednisone was started after biopsy with improvement in serum calcium (calcium 9.4 mg/dL). He was treated with Azithromycin and Ethambutol and discharged home a week after.

Conclusion
Granulomatous diseases like MAC, an AIDS-defining illness, cause hypercalcemia via activation of macrophages which express extrarenal 1- alpha -hydroxylase. It converts vitamin D to its active form 1,25(OH)2 vitamin D causing its excess, leading to hypercalcemia. Other potential causes of hypercalcemia such as malignancy must be ruled out as seen in our patient who had classic B symptoms with imaging suggestive of lymphoma. Treatment of hypercalcemia in granulomatous disease is aimed at treatment of the underlying disorder. It responds well to glucocorticoids and bisphosphonates.
Presentation: No date and time listed
LBODP023 Popular Supplements Containing Plant Extracts With High Biotin Content Can Severely Impact Parathyroid Hormone (PTH) Measurements Leading To A False Suspicion Of Primary Hyperparathyroidism (PHP).
Authors: Wozniak Zofia , Seroczynska Barbara 
Published: November 2022

Abstract

Introduction
Biotin interference has been recognised as an important factor to take into consideration when analysing discrepancies in laboratory test results of hormone measurements in a 2020 AACC guideline. 1 Little attention has been given yet to possible interference with compound supplements including plant extracts with high biotin content.

Clinical Case
A 64 year old woman has been observed in the outpatient clinic for hypothyroidism and Cushing syndrome resolved with adrenalectomy. Routine laboratory check monitoring vitamine D supplementation revealed parathyroid hormone (PTH) elevation- 138 pg/ml with slightly depressed vitamin D level- 24 ng/ml and calcium and phosphorus within normal limits (Ca- 9.3 mg/dl, Pi-2.88 mg/dl). Vitamin D supplementation has been elevated to 4000 IU per day and the PTH and vitamin D levels re-checked after 3 months. Vitamin D was still deficient- 27 ng/ml, PTH was 129 pg/ml. Two months later the patient was hospitalised to evaluate her post-cushing status and the results of Ca, Pi, PTH and vitamin D were reported to be within the normal ranges. Suspecting biotin interference the patient was advised to re- check the PTH levels in two different laboratories and the results differed significantly and were: 72 pg/ml checked with ECLIA method and 137 pg/ml for CMIA method. Suspecting biotin interference patient's history was re-evaluated for supplements and a compound supplement has been identified containing high quantities of pumpkin seed extract (260 mg/capsule) which contains substantial quantities of biotin. Identification of this confounding factor spared the patient further diagnostic procedures.

Conclusion
It is useful to consider other non-obvious sources of biotin in the form of compound supplements and plant extracts when encountering conflicting results of hormone measurements.1. AAC Guidance Document on Biotin Interference in Laboratory Tests. Journal of Applied Laboratory Medicine, 2020 May 1;5(3): 575-587.
Presentation: No date and time listed