bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI001 Tanycytic Thyroid-stimulating Hormone Receptor Activation Increases Blood-Hypothalamus Barrier Permeability And Induces Appetite In Female Mice
Authors: Kannangara Hasni Suhasha , Jocoll Burgess , Miyashita Sari , Gumerova Anisa , Korkmaz Funda , Witztum Ronit , Sims Steven , Cheliadinova Uliana , Pevnev Georgii , Moldavski Ofer , Frolinger Tal , Yuen Tony , Ryu Vitaly , Zaidi Mone 
Published: October 2023

Abstract
Disclosure: H.S. Kannangara: None. B. Jocoll: None. S. Miyashita: None. A. Gumerova: None. F. Korkmaz: None. R. Witztum: None. S. Sims: None. U. Cheliadinova: None. G. Pevnev: None. O. Moldavski: None. T. Frolinger: None. T. Yuen: None. V. Ryu: None. M. Zaidi: None.
In addition to its well-known action to trigger thyroid hormone production, thyroid-stimulating hormone (TSH) is released in the brain, and its receptor (TSHR) has been found in brain sites, including the tanycytes of the third ventricle, that regulate ingestive behavior and convey metabolic information across the blood-hypothalamus barrier (BHB). Our recent work highlights largely undiscovered role for TSHRs in the tanycytes. Here, we tested the hypothesis that tanycytic TSHR activation triggers rapid remodeling of BHB vascular permeability inducing appetite. We compared hypothalamic vascular permeability of food deprived (FD) and ad libitum fed (AL) Tshr+/- and their wild type (WT) counterparts exploiting transmission electron microscopy studies and immunofluorescence for constitutive tight junction protein Claudin-1 and homodimer glycoprotein MECA-32, primarily expressed in tanycytes and endothelial cells, respectively. Fasting significantly increased the organization of tanycytic honeycomb pattern of Claudin-1 and fenestral MECA-32-associated diaphragms in the median eminence and arcuate nucleus implying decreased BHB vascular permeability in Tshr+/- mice. Transmission electron microscopy confirmed immunofluorescence results. In a separate gain-of-function experiment, TSHR activation by the small molecule MS438 increased BHB vascular permeability as evidenced by decreased Claudin-1 and MECA-32 immunostaining. Tanycytic TSHR activation significantly increased both food foraging and intake as during one-hour refeeding after FD. Surprisingly, refeeding restored neuronal activation marker c-Fos expression in the paraventricular nucleus of the hypothalamus, parabrachial nucleus and nucleus of the solitary tract, though failed to do so in the paraventricular nucleus and nucleus of the solitary tract of MS438-injected mice. Collectively, these data infer that modulation of tanycytic TSHRs plays an important role in BHB plasticity in relation with ingestive behavior.
Presentation: Friday, June 16, 2023
FRI009 Microbiome Affects Host Metabolic Homeostasis Via Differential Regulation Of Gene Expression In The Endocrine System
Authors: Milhouse Wynne , Ren Hongxia 
Published: October 2023

Abstract
Disclosure: W. Milhouse: None. H. Ren: None.
Dysbiosis has been implicated in many metabolic disorders, but the exact role of microbiota is not completely understood. To address this question, we used germ-free (GF) and conventional (CON) mouse models to examine the expression of genes critical for endocrine regulation of metabolic homeostasis. Samples of the mediobasal hypothalamus (MBH) were obtained from 18 germ-free and 18 conventional C57BL/6 mice (n=9 males, 9 females). Each gene transcript was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). We also collected the serum from both cohorts and measured ad libitum insulin and leptin concentrations by enzyme-linked immunosorbent assay (ELISA). Our results showed that, in the MBH, GF mice had increased expression of neuropeptides involved in feeding regulation, i.e., Neuropeptide Y (Npy) and Proopiomelanocortin (Pomc), compared to CON mice (p &lt; 0.0001). Furthermore, CON mice had increased expression of a negative regulator of leptin signaling, Suppressor of cytokine signaling 3 (Socs3), in the MBH. Consistently, serum leptin in CON male mice was higher than that of male GF mice (p &lt; 0.001). In the gut samples, the GF cohort demonstrated increased expression of gut hormones that promote satiety, such as Peptide yy (Pyy) and Cholecystokinin (Cck), respectively (p &lt; 0.05 and p &lt; 0.0001). The absence of a microbiome had differing effects on the expression of incretin hormones and the G protein-coupled receptors (GPCRs) that stimulate their secretion. In the jejunum, ileum, and colon of CON mice, expression of Glucagon-like peptide 1 (Glp-1) was increased compared to that of GF mice (p &lt; 0.001, p &lt; 0.05, and p &lt; 0.0001, respectively). Conversely, Glucose-dependent insulinotropic polypeptide (Gip) showed increased expression in the duodenum of male and female GF mice (p &lt; 0.0001). G protein-coupled receptor 119 (Gpr119) and G protein-coupled receptor 120 (Gpr120) showed increased expression only in the colon of female GF mice (p &lt; 0.0001 and p &lt; 0.01, respectively). Germ-free and conventional mice demonstrated comparable ad libitum insulin concentrations. We conclude that the increased expression of Pomc, Gip, Cck, and Pyy and the increased leptin sensitivity in GF mice contribute to the lean phenotype observed in these mice. The additional increase in Npy and decrease in Glp-1 likely play a compensatory role in regulating energy consumption and expenditure. Thus, the microbiome may impinge upon diverse effectors of the neuroendocrine and enteroendocrine systems to regulate host metabolism, influencing energy consumption and expenditure in the development of obesity.
Presentation: Friday, June 16, 2023
FRI031 A Novel Strategy To Detect Leptin Receptor (Lepr, fa) Mutation In Obesity And Diabetic Animal Model (Zucker Rats)
Authors: Xu Xinyun , Hu Xinge , Ma Guodong , Wang Tiannan , Wang Jayne , Chen Guoxun , Zhao Ling , Chen Jiangang 
Published: October 2023

Abstract
Disclosure: X. Xu: None. X. Hu: None. G. Ma: None. T. Wang: None. J. Wang: None. G. Chen: None. L. Zhao: None. J. Chen: None.
Globally, diabetes is among the leading causes of premature morbidity and mortality. Early intervention is crucial to achieve optimal outcomes and minimize the burden of diabetes. Animal models are indispensable tools to investigate etiology and explore novel strategies for diabetes treatment and prevention. Zucker strain and its derivatives, Zucker Fatty (ZF) and Zucker Diabetic Fatty (ZDF) rats, are one of the most used rodent models to study diabetes and diabetes-associated metabolic disorders. Homozygous Zucker rats with leptin receptor gene mutation (Lepr, fa-/-) spontaneously develop obesity, hypercholesterolemia, and hyperlipidemia. The wildtype (fa+/+) and heterozygous (fa+/-) littermates phenotypically are indistinguishable. Furthermore, early stages of diabetes are asymptomatic, and the obese phenotype is not appreciable in homogenous (fa-/-) Zucker rats until week 4 of age. Therefore, a rapid, cost-effective, and reliable genotyping method is essential to differentiate homozygous (fa-/-) rats from either wildtype (fa+/+) or heterozygotes (fa+/-) in early interventional studies. We reported a tetra-primer Amplification-Refractory Mutation System (ARMS)—PCR approach to detect leptin receptor fa mutation using genome DNA collected from ear and tail tissues of Zucker rats. Three different types of amplicon patterns are easily identified by agarose gel electrophoresis. Wildtype (fa+/+) genotype displays a 401 bp and a 201 bp amplicon band; heterozygous (fa+/-) consists of a 401 bp, a 263 bp, and a 201 bp amplicon band on the gel; homozygous (fa-/-) comes up with two bands of 401 bp and 263 bp. The genotypes identified by our tetra-primer ARMS—PCR method are further confirmed by sequence analysis. This method requires neither DNA purification nor restriction enzyme digestion, which is suitable for research exploring gene-environment interaction, as well as implementing appropriate intervention approaches in the research areas of diabetes and metabolic diseases.
Presentation: Friday, June 16, 2023
FRI051 Lean Mass And Fat Mass Across Different Age Groups In The Thai Population
Authors: Charoenngam Nipith , Theerakulpisut Daris , Sribenjalak Dueanchonnee , Pongchaiyakul Chatlert 
Published: October 2023

Abstract
Disclosure: N. Charoenngam: None. D. Theerakulpisut: None. D. Sribenjalak: None. C. Pongchaiyakul: None.
Introduction: Lean mass and fat mass have been shown to influence the risks of cardio-metabolic disorders. While obesity is defined as body mass index (BMI) of more than 30 kg/m2 in White, Hispanic, and Black individuals and 25 kg/m2 in Asian individuals, the cut-off values for lean mass and fat mass in different populations are less well-defined as data on reference values of lean mass (LM) and fat mass (FM), especially in the Southeast Asians, are limited. In this study, we aimed to determine the normative values of LM and FM across different age groups in the Thai population. Methods: Male and female consecutive community-dwelling individuals aged 20 - 90 years were recruited from Srinagarind Hospital, Khon Kaen, Thailand between 2010 and 2015. LM and FM were measured using dual energy x-ray absorptiometry on a Lunar Prodigy bone densitometer (GE Healthcare, Madison, WI). Lean mass index (LMI) and fat mass index (FMI) were calculated [LMI = LM (kg)/height (m)2, FMI = FM (kg)/height (m)2]. Percentiles of each variable stratified by age and sex were calculated. SPSS version 27 (SPSS Inc., Chicago, IL) was used to perform statistical analysis. Results: A total of 832 individuals (334 males and 498 females) were included in the study. The mean ± SD age, LM, FM, LMI and FMI were 50.0 ± 16.2 years, 38.9 ± 8.0 kg, 15.5 ± 7.7 kg, 15.6 ± 2.3 kg/m2 and 6.4 ± 3.3 kg/m2, respectively. In males, the median LM decreased from with age from 49.4 kg in 20 - 29 years group to 42.3 kg in ≥70 years group. The median LMI was relatively unchanged from age 20 - 59 years at 17.7 - 18.0 kg/m2 and dropped to 16.4 kg/m2 in ≥70 years group. The median FM and FMI increased with age from 6.3 kg and 2.5 kg/m2 in 20 - 29 years group to 11.9 kg and 4.6 kg/m2 in 60 - 69 years group and dropped to 10.3 kg and 4.1 kg/m2 in ≥70 years group. In females, the median LM peaked at age 30 - 39 years at 34.6 kg and decreased with age to 30.8 kg in ≥70 years group. The median LMI peaked at age 40 - 49 years at 14.6 kg/m2 and decreased with age to 13.8 kg/m2 in ≥70 years group. The median FM and FMI peaked at age 50 - 59 years at 20.7 kg and 9.0 kg/m2 and decreased with age to 15.9 kg and 7.1 kg/m2 in ≥70 years group. Conclusion: We generated age-stratified normative values of LM, FM, LMI and FMI from the cross-sectional data of community-dwelling Thai individuals. We observed that LM achieved its peak during early adulthood (age 20 - 29 years in males and 30 - 39 years in females) and decreased with older age. On the other hand, an inverse-U shaped association between FM and age was observed as FM achieved its peak at age 60 - 69 years in males and 50 - 59 in females and decreased with older age.
Presentation: Friday, June 16, 2023
FRI060 Real World Experience Of Weight Management In Low Socioeconomic Community Clinic
Authors: West Brittany Ann , Mon Sann 
Published: October 2023

Abstract
Disclosure: B.A. West: None. S. Mon: None.
Pilot Study: Real-world experience of weight management in low socioeconomic community clinic
Introduction: Management of obesity and unhealthy behaviors is an essential step in patients with Prediabetes and T2DM, particularly those with socioeconomic status (SES) in whom obesity is more prevalent. While several behavior interventions targeting obesity exist, a successful adaptation of interventions in routine care is challenging especially in those with low SES. We examined the real word experience of weight loss management in our community clinic. Method: Retrospective chart review of consecutive patients seen in an endocrinology clinic at a hospital-based community clinic. Result: A total of 23 female patients, average age 48.4 ± 10.8 years, with average BMI 37.4 ± 6.9 kg/m2, were provided comprehensive lifestyle counseling focusing on nutrition, exercise, sleep health at each visits along with semaglutide at the highest tolerable dose of 2.4 mg/dl weekly. Within 6 months from the initiation of semaglutide and the weight loss intervention, 11/23 (48%) patients lost weight by &gt;5% from their baseline visit, and 17/20 (85%) patients at the end of 1 year. 12/20 (60%) and 6/20 (30%) lost weight at least by 10% and 15% respectively at the end of 1 year. Compared to the baseline data, weight ( 101.2±18.4) kg, SBP 127.6 ± 13.4 mmHg, HbA1C 6.0 ± 1.1 mg/dL, Total Cholesterol 182.1 ± 40.4 mg/dL, LDL 102.4 ± 35.8 mg/dL, most parameters were improved at the end of 6 and 12 months respectively: weight 91.0± 18.6 vs 88.4± 16.2 kg, SBP 125.2± 16.8 vs. 126.9± 15.6 mmHg, HbA1C 5.8 ± 1.2 vs 6.3 ± 1.4 mg/dl, Total cholesterol 178.9± 33.1 vs 175.0 ± 50.7mg/dl, LDL 100.4± 27.7 vs 101.8± 47.7 mg/dL. Conclusion: This real-world implementation study reported the benefits of weight loss and other clinical parameters after the intervention consisting of a combined health behavior counseling and use of semaglutide at the low-SES community clinic.
Presentation: Friday, June 16, 2023
FRI072 Biomechanical CT To Assess Bone After Sleeve Gastrectomy In Adolescents With Obesity- Prospective Longitudinal Study
Authors: Singhal Vibha , Huber Florian A , Tuli Shubhangi , Bouxsein Mary , Misra Madhusmita , Bredella Miriam A 
Published: October 2023

Abstract
Disclosure: V. Singhal: None. F.A. Huber: None. S. Tuli: None. M. Bouxsein: None. M. Misra: None. M.A. Bredella: None.
Background and Objective: Sleeve gastrectomy (SG) is effective in treating cardiometabolic complications of obesity but is associated with bone loss. Our aim was to determine the effect of SG on the lumbar spine by biomechanical computed tomography (CT) analysis in adolescents/young adults with obesity. We hypothesized that SG would lead to a decrease in strength and BMD compared to non-surgical controls. Methods: 12-month prospective non-randomized study of adolescents/young adults with obesity who either underwent SG (N=29) or were followed without surgery (controls, N=30). At baseline and 12 months, participants underwent QCT of L1 and L2 for biomechanical assessment and MRI of the abdomen and mid-thigh for body composition assessment. 12-month changes between groups were compared using Student’s t-test, and changes within groups were assessed using paired t-tests. Analyses were controlled for baseline and 12-month changes in BMI by multivariable analyses. Regression analysis was performed to evaluate the effect of body composition on bone parameters. Results: Participants in the SG group had a higher baseline BMI than controls (p=0.01) and lost an average of 34.3±13.6 kg 12 months after surgery, whereas weight was unchanged in controls (p&lt;0.001). There were significant reductions in abdominal adipose tissue and thigh muscle area in the SG group compared to controls (p&lt;0.001). Significant decreases in bone strength [-609 (-928, -291) vs. 103 (-173, 380) N], bending stiffness (-0.08 ± 0.16 vs. 0.07 ± 0.15 kNm/rad), average vBMD (-12 ± 12 vs. 0 ± 13 mg/cm3) and trabecular vBMD (-15 ± 13 vs. 2 ± 13 mg/cm³) were noted in the SG vs. control groups (all p&lt;0.001). After controlling for change in BMI, a 12-month reduction in cortical BMD was significant in the SG group compared to controls (p=0.02). Reductions in strength and trabecular BMD were associated with reductions in BMI, visceral adipose tissue, and muscle (p≤0.03). Conclusion: Adolescents undergoing SG had a decrease in strength and volumetric BMD of the lumbar spine compared to non-surgical controls; reductions in cortical BMD were independent of weight reductions over the study duration. These changes were associated with a decrease in visceral fat and muscle mass.
Presentation: Friday, June 16, 2023
SAT161 The Impact Of A Very Low-calorie Diet On Reversal Of Metabolic Disorders Among Indian Subjects: A Real World Clinic-based Study
Authors: Deshpande Neeta , Kapoor Nitin 
Published: October 2023

Abstract
Disclosure: N. Deshpande: None. N. Kapoor: None.
Introduction: Reversal/remission of diabetes has been tested and well proven in the Caucasians. However, the Asian Indian phenotype is genetically and clinically distinct and there is a lack of robust data on this subject. Also, hitherto, the benefits of such an intervention have been reported only in a tightly monitored trial-based environment, but its efficacy from real-world data in busy clinical practices is lacking from the Indian subcontinent. In this study we aimed to study the impact of marked reduction of calorie intake on obesity indicators and diabetes related comorbidities in subjects of Indian ethnicity in a clinic-based cohort. Material and Methods: A 3-month structured Reversal Diet of 800-830 calories/day, comprising an inhouse packed commercially available meal replacement liquid formula, along with non-starchy veggies/soups/ diluted buttermilk, and fat replaced all 3 major meals. Clinical and biochemical metabolic parameters were assessed at baseline and at 3 months. Only those subjects who completed the 3-month assessment were included. Body composition was analyzed using bioimpedance with the INBODY 230 Analyser. Statistical analysis was undertaken using the SPSS 16·0 software package. This study was approved by the Institutional Review Board. Results: 374 subjects were included of which 117(31.2%) had type 2 Diabetes (T2DM). At baseline the mean (SD) age of the participants was 40.1(12.4) years and 333/374(89.1%) participants were women. There was significant improvement in body weight (85.4 Vs 77.7 Kg), BMI (32.6 Vs 29.8 kg/m2), Waist circumference (103.6 Vs 98.3 cm) and hip circumference (109.2 Vs 103.8 cm) at 3 months, compared to baseline. Body fat % changed from 41.9 to 37.6 and other anthropometric indicators (neck circumference, thigh circumference and arm circumference) were also significantly better after the intervention (P&lt; .001). Among subjects with T2DM (31.2%), 40% had remission in diabetes, 28% of insulin users stopped insulin and about 30% stopped oral anti diabetic agents. Even among those who did not go into diabetes remission, Insulin was stopped in 29% and reduced in 38%, Oral Anti Diabetic agents reduced in 22%, blood pressure was normalized without medicines in 14% and NAFLD remission was attained in 41% of patients. Conclusion: A significant impact towards reversal of metabolic disorders was observed following a structured very low-calorie diet intervention, in this clinic-based cohort. Further follow-up studies are currently needed to provide long term evidence on the sustainability and long-term efficacy of such an intervention in the metabolically unique Indian population.
Presentation: Saturday, June 17, 2023
SAT653 Conditional Knockout Of Neural Sarm1 Improves Body Mass And Metabolic Health With High Fat Diet
Authors: Dabill Lila , Shen Ivana , Zhang Xiao , DiAntonio Aaron , Scheller Erica 
Published: October 2023

Abstract
Disclosure: L. Dabill: None. I. Shen: None. X. Zhang: None. A. DiAntonio: None. E. Scheller: None.
Sterile alpha and TIR motif containing 1 (Sarm1) is a toll-like receptor, highly expressed in the nervous system, that is activated with injury, inflammation, and oxidative stress to promote axon degeneration and dysfunction. Previous findings with global knockout of Sarm1 showed evidence of metabolic improvements in high-fat diet (HFD) induced type 2 diabetes (T2D) as well as reduced peripheral axon degeneration. We hypothesize that this is due to the actions of Sarm1 in the nervous system. To test this hypothesis, we used Baf53b-Cre to knock out Sarm1 in all neurons throughout the body (Sarm1-cKO). Both control and Sarm1-cKO mice were fed HFD for 24 weeks, starting at 4-6 weeks of age. Quantitative PCR (qPCR) analysis confirmed high Sarm1 expression in the dorsal root ganglia (DRG) with a significant decrease in Sarm1-cKO mice; no significant difference in Sarm1 expression was observed in bone, testis, liver, iWAT, or brain tissue between control and Sarm1-cKO mice. Over the 24-week study period, Sarm1-cKO mice fed HFD gained 20% less body mass than controls (20.8g mass gain on average in cKO vs 26g mass gain in control mice). Furthermore, subcutaneous inguinal fat, but not visceral gonadal fat, was preferentially reduced by 26% in Sarm1-cKO mice. Sarm1-cKO mice on HFD also showed evidence of metabolic rescue with smaller livers and less steatosis. Lastly, insulin tolerance testing (ITT) results suggest that Sarm1-cKO mice on HFD were more sensitive to insulin than controls. Sarm1 inhibitors are currently under clinical development for the treatment of neurodegenerative disease. These results show that inhibition of Sarm1-dependent neurometabolic regulatory pathways also has the potential to support metabolic health in settings of obesity and T2D.
Presentation: Saturday, June 17, 2023
SAT146 Recurrent Hypoglycemia Following Asparaginase Therapy For Childhood Cancer: Institutional Experience
Authors: Tantoush Manal 
Published: October 2023

Abstract
Disclosure: M. Tantoush: None.
Background: Asparaginase (ASP) is a cornerstone pediatric leukemia and lymphoma therapy. Hyperglycemia following ASP is described, but hypoglycemia is infrequently identified as a complication. Following hypoglycemic events in children receiving ASP therapy, evaluation of associations and outcomes was undertaken. Aim: Evaluate and describe the risk factors, prevalence, duration, severity, recurrence and outcomes of children developing ASP-induced hypoglycemia. Method: Retrospective cohort study using electronic medical records to identify all patients who received ASP (PEGylated or non-PEGylated), and had diagnosis of hypoglycemia between 6/1/2017 and 6/30/22 at Texas Children's Hospital. We defined ASP-induced hypoglycemia as blood glucose (BG) &lt;70 mg/dl 2-8 weeks from ASP administration, without alternative causes. If hypoglycemia evaluation was completed, hyperinsulinism was defined by: BG &lt; 50 mg/dL; insulin &gt; 2 mIU/mL; β-hydroxybutyrate &lt; 1.8 mmol/L; free fatty acids &lt; 1.7 mmol/L; or a post-glucagon BG &gt; 30 mg/dL. Demographic and clinically relevant data were collected. Descriptive analysis was completed. Univariate regression models using Stata16 were analyzed. A p-value &lt;0.05 was statistically significant. Results: Patients receiving ASP totaled 722, with 56 (7.6%) having ASP-induced hypoglycemia. Cancer diagnosis included acute lymphoblastic leukemia (n=50), lymphoblastic lymphoma (n=5) or acute myeloid leukemia (n=1). Median age was 4.4 years (IQR: 2.6 - 8.1), with 46% Hispanic and 59% male. Median BMI z-score was +0.4 (IQR: -0.3 - 1.2). Initial hypoglycemia event was during Induction therapy in 86% (n=48), with median time from ASP to hypoglycemia diagnosis 11 days (IQR: 6-15). Median lowest BG was 51 mg/dL (IQR: 43-57) with median duration 11 days (IQR: 7-19). Treatment included dietary change (52%, n=29), cornstarch (29%, n=16), and continuous feedings (13%, n=7). Continuous BG monitoring was utilized in 9 (16%). A critical sample was obtained in 18 (32%) with all evaluations consistent with hyperinsulinism. Recurrent hypoglycemia with subsequent ASP doses occurred in 42 (74%), with a median duration 14 days (IQR: 8-21; max: 56 days). Overall cancer survival following ASP-induced hypoglycemia was 80% (85% if excluding relapse disease), with 3 years’ median follow up. Severity of hypoglycemia (lowest BG, number of events, or length of events) was not associated with age, sex, ethnicity, or BMI z-score in univariate analysis. Conclusion: ASP-induced hypoglycemia is relatively common, often recurs with subsequent dosing, and may become severe requiring intensive therapy. Prospective screening of patients receiving ASP may be appropriate to prevent and manage events. Patients completed chemotherapy without change in survival at 3 years’ follow-up. Further studies to elucidate prognostic factors of ASP-induced hypoglycemia are needed.
Presentation: Saturday, June 17, 2023