bluuebunny/crossref_metadata_2025_split huggingface dataset:
1581-P: Evaluation of a Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD) Clinical Pharmacy Service
Authors: SALLAM SANDY , AHMED AIJAZ , GU XIN 
Published: June 2024

Introduction & Objective: The purpose of this study is to evaluate the impact of pharmacist integration into the management of patients with MASLD. There are no known studies to date that have investigated the impact of a pharmacist integration within a hepatology clinic for MASLD management. The primary objectives are pharmacist intervention types and 6 month and 12 month clinical outcomes.
Methods: This is a retrospective cohort study of 220 patients referred to the clinical pharmacy service and/or a group patient education program coordinated by the pharmacist, between July 2018 to December 2021. Inclusion criteria included adult patients with established care at a Hepatology clinic with a formal diagnosis of MASLD by liver biopsy or non-invasive testing who have at least one cardiometabolic risk factor. Information on patient demographics, pharmacist interventions, and baseline, 6 month, and 12 month post-intervention clinical parameters were collected from the Electronic Medical Record. Data was analyzed using descriptive statistics, Paired t test, and Wilcoxon Signed Rank Test.
Results: Majority of patients were living with obesity (74.1%) and had Alanine Transaminase (ALT) elevations at baseline (60%). The most frequent pharmacist intervention was cardiometabolic medication recommendations. Weight loss from baseline was demonstrated at 6 months (5.09 lbs, p&lt;0.05) and maintained at 12 months (6.9 lbs, p&lt;0.05). Reduction in ALT was also observed at 6 months (14.38 U/L, p&lt;0.05) and 12 months (20.15 U/L, p&lt;0.05). Reductions were seen in Hemoglobin A1c (0.26%, p&lt;0.05), Low-Density Lipoprotein (9.23mg/dL, p&lt;0.05), and Triglycerides (16.63mg/dL, p=0.0629) at 12 months.
Conclusion: Patients referred to this novel clinical pharmacy service demonstrated significant and sustained weight and ALT reduction at 12 months, which may translate into MASLD improvement. They also experienced significant improvements in most cardiovascular clinical parameters.

Disclosure
S. Sallam: None. A. Ahmed: Advisory Panel; Novo Nordisk. X. Gu: None.
1586-P: Association between PCSK7 Levels and NAFLD Severity in KADEM Study
Authors: QADDOUMI MOHAMMAD , ABUBAKER JEHAD , AL-KHAIRI IRINA , CHERIAN PREETHI T. , SRIRAMAN DEVARAJAN , THANGAVEL ALPHONSE T. , CHANNANATH ARSHAD M. , ABDUL-GHANI MUHAMMAD , ALMULLA FAHD , ABU-FARHA MOHAMED 
Published: June 2024

Introduction: The increased obesity rates worldwide are associated with increased rates of Non-alcoholic fatty liver disease (NAFLD). Proprotein Convertase Subtilisin/Kexin type 7 (PCSK7) is an enzyme involved in lipid metabolism but its role in the development and progression of NAFLD remains unclear. This study aims to investigate the association between PCSK7 levels and NAFLD severity.
Methods: A total of 255 participants were recruited in KADEM study and screened for NAFLD using liver FibroScan machine. Participants were divided into two groups based on controlled attenuation parameter (CAP) scores: 208 dB/m with CAP scores above 294 dB/m, and 47 with CAP scores &gt;294 dB/m. PCSK7 levels were measured using ELISA.
Results: PCSK7 levels were higher in people with a CAP score &gt;294 dB/m, with levels of 0.9 ± 0.1 ng/mL compared to 0.5 ± 0.1 ng/mL in individuals with CAP scores lower than 294 dB/m (p=0.022). When the population was divided into tertiles based on CAP scores, PCSK7 levels were 0.30 ± 0.1 ng/mL for CAP scores ≤229, 0.7 ± 0.1 ng/mL for CAP scores between 230-271, and 0.8 ± 0.1 ng/mL for CAP scores ≥272 (p&lt;0.001). PCSK9 levels were positively associated with CAP score (r=0.387, p&lt;0.001), HbA1C (r=0.497, p&lt;0.001), FBG (r=0.497, p&lt;0.001), insulin (r=0.497, p&lt;0.001), HOMA-IR (r=0.480, p&lt;0.001), TG (r=0.366, p&lt;0.001), LDL (r=0.133, p=0.049), and VLDL (r=0.366, p&lt;0.001), while negatively associated with HDL (r=-0.271, p&lt;0.001).
Conclusion: Our findings indicate a significant association between elevated PCSK7 levels and increased NAFLD severity implicating a potential role for PCSK7 in NAFLD pathogenesis.

Disclosure
M. Qaddoumi: None. J. Abubaker: None. I. Al-khairi: None. P.T. Cherian: None. D. Sriraman: None. A.T. Thangavel: None. A.M. Channanath: None. M. Abdul-Ghani: None. F. Almulla: None. M. Abu-farha: None.

Funding
Dasman Diabetes Institute (RA HM-2019-030)
1587-P: Guideline-Directed Interventions and Diabetes Education in Improving Liver Health in Type 2 Diabetes Mellitus—An Observational Study of FIB-4 and Liver Stiffness Metrics
Authors: PADHYE DAKSHATA 
Published: June 2024

We evaluated the efficacy of guideline-directed intervention and diabetes education for lifestyle modification in liver health in T2DM on active treatment (n=229). We performed a comparative analysis of baseline and follow-up FIB-4 and liver stiffness measures. The FIB-4 scores slightly decreased on average from baseline (mean 2.478) to the last assessment (mean 2.362), with a wider variation in the data at the last measure (increased standard deviation). Median values remained consistent at 2. Liver stiffness measures (kPa) decreased on average from 14.59 to 13.7 with a consistent range of variability. The median decreased from 10.9 to 8.9, suggesting an overall improvement in liver stiffness. BMI values remained relatively stable from baseline (mean 30.03) to follow-up (mean 30.08), with a slight increase in variation and a higher maximum value at the last measurement. The study showed a marginal but positive trend in liver health, with a slight decrease in FIB-4 scores and a more notable improvement in liver stiffness, indicating potential therapeutic benefit. Despite these improvements, BMI values remained stable, indicating that the positive liver outcomes may not be directly associated with changes in body weight. Further investigation may be required to understand the underlying factors contributing to liver health improvements.

Disclosure
D. Padhye: None.
1588-P: Galectin-3 Inhibitor Protect ApoE Knockout Mice against Metabolic Dysfunction–Associated Steatohepatitis
Authors: ARAUJO LAYANNE , SUCUPIRA FELIPE , AMARAL ANDRESSA , PAULO CAMPOREZ JOAO 
Published: June 2024

Metabolic-dysfunction associated steatohepatitis is characterized by steatosis, inflammatory infiltrate and hepatocellular ballooning, and it can present fibrosis. The aim of work was to evaluate the effect of modified citrus pectin (MCP), inhibitor of galectin-3, in ApoE KO mice fed a western diet (WD). ApoE KO mice were divided into 3 groups: standard diet-fed (SD) group, WD-fed group, and WD-fed + MCP-treated group (WD+MCP). MCP treatment inhibited the increase of glucose tolerance, glycemia, plasma insulin and HOMA-IR, when compared to WD group. MCP treatment was able to inhibit the increase of TAG in the tissue by 9%, plasma TAG and VLDL, however had no significant difference for cholesterol and fatty acids in relation to WD group. We analyzed the expression of genes involved in the lipogenesis pathway in the liver (SREBP1, ACC, SCD1 and FASn). Only ACC gene expression was increased by 10x and SREBP1 protein expression by 183% in the WD group compared to the SD group. And the MCP treatment inhibited the increase of both. We also analyzed the collagen deposition and expression of genes involved in the collagen production (TGF-Beta, Col1alpha, MMP2), and MCP treatment inhibited the increase in collagen deposition by 8.2% and only MMP2 gene expression. The inflammatory profile of the liver was also shown, MCP treatment inhibited the increase of expression of F4/80, gene expression of cytokines (TNFa, IL-1b) and pJNK protein activity. We concluded that galectin-3 inhibition by the treatment with MCP protects ApoE KO mice against the development of MASH and insulin resistance

Disclosure
L. Araujo: None. F. Sucupira: None. A. Amaral: None. J. Camporez: None.

Funding
Spo Paulo State Research Support Foundation (2020/09094-1 and 2018/04956-5)
1597-P: High Fat and Fructose Diet Dysregulates Postprandial Gut and Hepatic Metabolism in a Canine Model
Authors: KRAFT GUILLAUME , SCOTT MELANIE , FARMER BEN , YANKEY KALISHA , EDGERTON DALE S. , RAJAGOPALAN HARITH , COZZI EMILY , GIBSON-CORLEY KATHERINE , FLYNN CHARLES R. , CHERRINGTON ALAN D. 
Published: June 2024

Diets high in fat and sugar are associated with the development of metabolic disease, but pathogenic changes in the gut and downstream metabolic organs are not well understood. In the dog, we sought to assess 9 weeks of chow (n=5) versus high-fat, high-fructose diet (HFFD) (n=5) on the gut response and the impact on liver, pancreas fat, and muscle following a mixed meal (26g protein, 67g carbohydrates, 22g lipids). To measure the 6-hour postprandial rate of nutrient absorption and secretion of pancreatic and gut hormones, dogs underwent surgical placement of catheters in the portal vein, hepatic vein, and femoral artery, and flow probes around the portal vein and hepatic artery. Duodenal morphology and L and K cell distribution were evaluated. The meal-induced glucose absorption occurred rapidly with HFFD (peak 13.5±1.1 mg/kg/min at 90 min post-meal v 10.9±1.3 mg/kg/min at 120 min), resulting in a greater rise in glucose (231±25 v. 162±7 mg/dL, p=0.03) compared to chow. Insulin secretion rates for HFFD and chow groups were similar at the 90 min peak (1.6±0.3 v. 1.9±0.6 µU/kg/min) and 6h AUC (237±46 v 243±67 mU/kg). Meal-induced GIP secretion was markedly increased (542±70 v 295±74 pg/kg/min, p=0.05) while GLP-1 was reduced (100±40 v 219±64 pg/kg/min, p=0.16) in HFFD compared to chow. These changes were associated with increased duodenal total mucosal height (1817±133 v 1500±159 µm, p=0.04) but no change in L or K cell distribution. HFFD-induced liver response was markedly altered with a failure to switch from net hepatic glucose output pre-meal to glucose uptake and storage post-meal (output of 1.7±0.2 to output of 3.0±1.4 mg/kg/min) compared to chow (output of 1.6±0.3 to uptake of 3.4±1.1). Given the lack of hepatic uptake, meal glucose was likely taken up by muscle.
In conclusion, HFFD-induced changes in duodenal morphology, gut function, and gut hormone secretion that were associated with abnormal hepatic and pancreatic responses, suggesting a role for the gut in metabolic pathogenesis.

Disclosure
G. Kraft: None. M. Scott: None. B. Farmer: None. K. Yankey: None. D.S. Edgerton: None. H. Rajagopalan: Board Member; Fractyl Health, Inc. Employee; Fractyl Health, Inc. Stock/Shareholder; Fractyl Health, Inc. E. Cozzi: Employee; Fractyl Health, Inc. Stock/Shareholder; Fractyl Health, Inc. K. Gibson-Corley: None. C.R. Flynn: None. A.D. Cherrington: Consultant; Abvance Therapeutics. Research Support; Abvance Therapeutics. Advisory Panel; AdipoPharma. Research Support; Cellular Longevity, Inc. dba Loyal. Advisory Panel; Fractyl Health, Inc. Consultant; Fractyl Health, Inc. Research Support; Fractyl Health, Inc. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Consultant; Paratus, Portal Insulin. Advisory Panel; Sekkei Bio, Sensulin Labs, LLC. Consultant; Thetis Pharmaceuticals, LLC.

Funding
Fractyl Health
1602-P: Exercise Training Reverses Skeletal Muscle DRP1 Hyperactivation and Improves Respiratory Capacity in Patients with Type 2 Diabetes
Authors: HEINTZ ELIZABETH C. , DANTAS WAGNER S. , ZUNICA ELIZABETH R.M. , BELMONT KATHRYN , MEY JACOB T. , BEYL ROBBIE A. , HSIA DANIEL S. , PARRY HAILEY A. , GLANCY BRIAN , HOPPEL CHARLES L. , AXELROD CHRISTOPHER L. , KIRWAN JOHN P. 
Published: June 2024

Introduction: Chronic activation of DRP1 promotes mitochondrial network fragmentation and restricts skeletal muscle glucose uptake in patients with type 2 diabetes (T2D). The purpose of this study was to determine if exercise reverses hyperactivation of skeletal muscle mitochondrial fission in patients with T2D.
Methods: 24 sedentary adults (49 ± 10 years) with obesity (BMI 36 ± 6 kg/m2) and T2D (HbA1C 7.3 ± 1.3%; 1.3 ± 1.2 glucose lowering medications) were randomized to 12 wks of exercise training (Ex; n=11) or standard care (Ctrl; n=13). Participants randomized to Ex performed supervised aerobic exercise 5 d/wk for 60 min/session at 80-85% HRMAX. Participants underwent a 3-day inpatient stay consisting of DXA, VO2peak, and 2-stage hyperinsulinemic-euglycemic clamp at baseline and post intervention. Skeletal muscle biopsies were obtained for Western blot, high-resolution respirometry, and ion beam scanning electron microscopy with machine learning segmentation. Relative changes from baseline were calculated, and comparisons were made with unpaired Student’s t-tests. The primary outcome was change in pDRP1Ser616 expression.
Results: Age, sex, body weight, and diabetes status were similar at baseline (p&gt;0.05). Ex increased VO2peak, lean mass, and peripheral insulin sensitivity and reduced fat mass relative to Ctrl (all p&lt;0.05). Skeletal muscle pDRP1Ser616 was reduced in Ex (p&lt;0.05) independent of PGC-1α and AMPK. Ex increased maximal NADH-linked OXPHOS (p&lt;0.05) and improved succinate- and complex III-linked OXPHOS (p&lt;0.1). Mitochondria were elongated and had reduced sphericity after Ex (p&lt;0.001).
Conclusions: Exercise training reversed hyperactivation of skeletal muscle mitochondrial fission and improved respiratory capacity independent of biogenesis. Collectively, these data indicate that exercise improves skeletal muscle insulin sensitivity in T2D, in part, by restoring mitochondrial dynamics and networking.

Disclosure
E.C. Heintz: None. W.S. Dantas: None. E.R.M. Zunica: None. K. Belmont: None. J.T. Mey: None. R.A. Beyl: None. D.S. Hsia: None. H.A. Parry: None. B. Glancy: None. C.L. Hoppel: Advisory Panel; Cytokinetics Inc. C.L. Axelrod: None. J.P. Kirwan: None.

Funding
National Institutes of Health (DK108089 and GM104940)
1603-P: The Cardiovascular Impact of Appropriately-Timed Prandial Insulin in Type 1 Diabetes—A Randomized Crossover Study
Authors: HORTON WILLIAM B. , LOVE KAITLIN , JAHN LINDA , HARTLINE LEE , AYLOR KEVIN W. , BARRETT EUGENE 
Published: June 2024

Introduction & Objective: Appropriately-timed (i.e., ~15 minutes before meal intake) prandial insulin administration improves postprandial glycemic control, but the cardiovascular impact of this intervention is unknown. In this study, we tested whether appropriate prandial insulin timing improves insulin’s microvascular action in people with type 1 diabetes (T1D).
Methods: The primary outcome was change in myocardial microvascular perfusion (via contrast-enhanced ultrasound) and secondary outcome was change in skeletal muscle microvascular perfusion. Following overnight fast, participants underwent baseline measures of microvascular perfusion and then consumed a standardized liquid mixed meal (10 kcal/kg body weight). Vascular measurements were then repeated 120 minutes later. 18 participants with T1D completed two admissions with a randomized crossover design: (A) prandial insulin injected 15 minutes before meal intake and (B) prandial insulin injected 15 minutes after meal intake began. Plasma insulin and glucose were measured every 30 minutes. Repeated measures ANOVA compared changes in insulin and glucose while paired and unpaired t-tests compared changes in microvascular outcomes.
Results: Myocardial microvascular blood flow was similar at baseline between the two admissions. Change in plasma glucose was greater (p&lt;0.01) and plasma insulin was higher (54.43 vs 41.42 µIU/mL; p&lt;0.01) at the 120-minute mark in Admission B compared to Admission A. Myocardial microvascular blood flow increased (p=0.03) in Admission A while it modestly decreased (p=0.08) in Admission B. There were no changes in skeletal muscle microvascular perfusion during either admission.
Conclusion: Appropriately-timed prandial insulin administration improved glycemic control and myocardial microvascular perfusion two hours after meal intake. Future work could investigate whether such improvements, occurring repetitively, can improve cardiovascular health.

Disclosure
W.B. Horton: None. K. Love: None. L. Jahn: None. L. Hartline: None. K.W. Aylor: None. E. Barrett: None.

Funding
American Heart Association (941481); Juvenile Diabetes Research Foundation (3-SRA-2023-1236-M-B)
1612-P: AGE Breaker Ameliorates Diet-Induced Hyperglycemia and Muscle Atrophy through Modulating Metabolic Memory in Muscle
Authors: TING HSIAO WEI , LEE CHIEN-WEI , LEE YUK-WAI 
Published: June 2024

Metabolic memory reflects lasting effects of pre-exposed stimulations which can be manifested in transcription, translation, etc. It is also associated with diabetes progression and complications but lacks effective prevention strategies. To determine the impact of metabolic memory on the early disease stage, skeletal muscle with insulin resistance happened at early stage was chosen as study model. Given that advanced glycation endproduct (AGE) signaling and AGE-induced ECM changes have been reported to play crucial role in diabetes development, this study aimed to determine whether oral ALT711 AGE breaker administration could enhance the recovery of high-fat diet (HFD) induced hyperglycemia, and muscle structural and functional perturbations through modulating metabolic memory in male mice. We used 12-week-old male C57BL/6J mice with chow or repeated HFD feeding and ALT711 (20mg/kg/day) administration. GA muscle bulk RNA sequencing (n=3) identified DEGs with metabolic memory profiles. Mice (n=6) were sacrificed at specified time points, and extensor digitorum longus (EDL) and gastrocnemius (GA) muscles were collected for functional and structural assessment. Statistical analysis was conducted using two-way ANOVA. The GA muscle bulk RNA sequencing results revealed HFD-induced DEGs with a metabolic memory profile, which was associated with ECM remodeling and AGE signaling, and was validated by histology and QPCR. HFD-induced changes in muscle contraction, relaxation properties, and stiffness also displayed metabolic memory profiles. The administration of ALT711 significantly prevented the onset of HFD-induced weight gain and hyperglycemia and demonstrated a reduced extent of metabolic memory phenotypes. Our findings indicate the potential of the AGE breaker for diabetes and weight management, improving muscle quality by reducing metabolic memory. This offers a new avenue for mitigating hyperglycemia onset and progression.

Disclosure
W. Hsiao: None. C. Lee: None. Y. Lee: None.

Funding
Area of Excellence (AoE/M-402/20); General Research Fund (14104620); Start-up grant from Chinese University of Hong Kong (4930991 and 4930992); National Science and Technology Council, Taiwan (111–2320-B-039–070-MY3); Center for Neuromusculoskeletal Restorative Medicine (CT1.1)
162-OR: Sustained TNF-a Transcription Triggered in Obesity through H3K9/K18 Acetylation Is Associated with Metabolic Impairments
Authors: AHMAD RASHEED , BAHMAN FATEMAH , KOCHUMON SHIHAB P. , JACOB TEXY K. , ALRASHED FATEMA , WILSON AJIT , AREFANIAN HOSSEIN , THOMAS REEBY S. , AKHTER NADEEM , AL-MANSOUR NOURAH , ALBELOUSHI SHAIMA , AL MADHOUN ASHRAF , SINDHU SARDAR T.A.K. , ALZAID FAWAZ , ALMULLA FAHD 
Published: June 2024

Obesity-induced metabolic inflammation contributes to the development of various metabolic disorders and can be induced by the consumption of high-fat diets (HFD) rich in saturated fatty acids. The role of the TNF-α in metabolic dysfunction is now clear, although the pathways that promote and sustain the transcriptional regulatory process of the TNF-α gene under the setting of obesity remain incompletely understood. To identify the obesity-mediated transcriptional regulatory program of TNF-α, we used a murine model of diet-induced obesity (DIO). Male C57BL6/J mice were fed a palmitate oil-based HFD or a control diet (CD) for 16 weeks. Compared to CD, mice with DIO displayed elevated levels of TNF-α along with increased acetylation levels of epigenetic marks histone H3 lysine 9 and 18 acetylation (H3K9/K18) in adipose tissue and liver. Determination of permissive histone acetylation marks in the promoter region of TNF-α in both adipose tissue and liver was achieved through the Chromatin Immunoprecipitation (ChIP) assay. ChIP-qPCR analysis data show that obesity led to increased levels of the transcriptionally permissive acetylation marks H3K9/K18 in the TNF-α promoter in adipose tissue and liver compared to lean mice. Increased TNF-α expression in obese adipose tissue and fatty liver at the chromatin level corresponds to the changes in the level of histone acetylation marks H3K9/K18. Moreover, TNF-α and histone acetylation marks are positively associated with body weight gain, insulin resistance, and liver steatosis.
In conclusion, our findings support a model in which DIO creates a setting for sustained transcriptional regulation of the TNF-α gene via chromatin remodeling, enabling TNF-α to contribute to metabolic dysfunction. We also propose that acetylation of H3K9/H3K18 may be considered valuable prognostic factors for metabolic impairment and liver steatosis in obesity.

Disclosure
R. Ahmad: None. F. Bahman: None. S.P. Kochumon: None. T.K. Jacob: None. F. Alrashed: None. A. Wilson: None. H. Arefanian: None. R.S. Thomas: None. N. Akhter: None. N. Al-Mansour: None. S. AlBeloushi: None. A. Al Madhoun: None. S.T. Sindhu: None. F. Alzaid: None. F. Almulla: None.
1629-P: Seven-Month HFD Feeding Abolishes the Protective Effect of STING Disruption on Obesity-Associated Hepatic Steatosis, Inflammation, and Insulin Resistance
Authors: GUO XINLEI , LI HONGGUI , WU CHAODONG 
Published: June 2024

Insulin resistance (IR) means the failure of cells to respond normally to insulin, commonly associated with obesity and causing various metabolic dysregulations in type 2 diabetes. As a mediator of innate immunity, stimulator of interferon genes (STING) in human subjects is positively correlated with excessive fat deposition and liver inflammation, which both trigger hepatic and systemic IR. Also, STING expression is increased in insulin-responsive tissues in mice fed a high-fat diet (HFD) for 3 months, coupled with the decreased sensitivity of systemic insulin signaling. However, it is unknown about the effect of STING on IR in mice upon prolonged HFD feeding, which reflects the long-term course of human obesity. In this study, wild-type (WT) and STING-disrupted (STgt) male mice were fed an HFD for 3 months and examined for obesity and IR. Some HFD-fed mice were examined for hepatic insulin signaling upon a bolus injection of insulin into the portal vein. Additional STgt and WT mice were fed an HFD for 7 months and examined for obesity and systemic insulin sensitivity. Compared to male 3-m-HFD-WT mice, male 3-m-HFD-STgt mice gained smaller body weights and decreased levels of hepatic steatosis and inflammation, along with increased response to insulin. Consistently, insulin-stimulated Akt phosphorylation in the liver, adipose tissue, and skeletal muscle from male 3-m-HFD-STgt mice were much greater than those in the respective tissues from male 3-m-HFD-WT mice. However, upon prolonged HFD feeding, STgt mice displayed notably increased severity of obesity, hepatic steatosis and inflammation, all of which cause hepatic and systemic IR, relative to WT or STgt mice upon 3-month HFD feeding. These results indicate HFD feeding for 7 months abolishes the protective effect of STING deletion on obesity-associated hepatic steatosis/inflammation, and IR. As such, diets approach is key in managing obesity-induced metabolic diseases.

Disclosure
X. Guo: None. H. Li: None. C. Wu: None.

Funding
National Institutes of Health (DK124854)