bluuebunny/crossref_metadata_2025_split huggingface dataset:
2028-LB: Investigate Sex- and Fat Depot–Specific Glucose Metabolism after Consuming Carbohydrate-Enriched Diets with (Un)interrupted Prolonged Sitting
Authors: KUO FENG-CHIH , CHEN YUNG-CHIH 
Published: June 2024

Introduction & Objective: Carbohydrate-enriched diets and sedentary behavior are risk factors for diabetes. However, their impacts on glucose metabolism in abdominal and gluteal subcutaneous adipose tissues, especially considering sex differences, remain unexplored.
Methods: Twenty healthy subjects (10 females) [age 30.5±7.5 years, BMI 22.9±2.2 kg/m2 (mean±SD)] participated in mixed-feeding trials lasting 320 minutes, with breakfast and lunch containing 77% carbohydrates and either prolonged sitting (SIT) or interrupted prolonged sitting (2 min walking at 6.4 km/h every 20 min) (ACTIVE) in a randomized crossover design. Continuous glucose monitoring (CGM) was inserted simultaneously at abdominal (ABD) and gluteal (GLUT) fat-depots. Body composition was precisely quantified by dual-energy x-ray absorptiometry. Oral glucose tolerance test was performed for measuring insulin sensitivity and resistance. In vitro experiments using paired human abdominal and gluteal preadipocyte cell lines were conducted to investigate molecular mechanisms.
Results: In the SIT trial, GLUT CGM showed a slower increase in interstitial blood glucose (BG) during lunch compared to ABD CGM, particularly in females. Interrupted prolonged siting (ACTIVE trial) led to numerically lower BG levels in both ABD and GLUT CGM, with the most significant impact observed in female ABD CGM. While males with higher insulin resistance and android fat displayed a notable correlation with decreased BG levels in the ACTIVE trial. Our in vitro experiments further revealed steady glucose uptake (GLUT1 expression) and de novo lipogenesis (ChREBP protein) were significantly enhanced in gluteal adipocytes during post-feeding 3 to 6 hours.
Conclusion: Breaking prolonged sitting improves glucose control and gluteal fat depot may play roles to stabilize carbohydrate-enriched diets related hyperglycemia.

Disclosure
F. Kuo: None. Y. Chen: None.

Funding
TSGH-E-112257
2042-LB: The Gut–Fat Cross Talk in Metabolic Regulation through Microbiome
Authors: ZHANG ERYUN , CEBALLOS HANNAH M. , HUANG WENDONG 
Published: June 2024

Current treatments are still limited in their ability to mitigate obesity and its complications. Obesity develops due to an imbalance between nutrient intake and energy expenditure; therefore, there is an urgent need to better understand the mechanisms governing nutrition and energy balance, with the long-term goal of developing novel strategies to treat obesity and associated metabolic diseases. Our previous study uncovered a novel link between intestinal AMPK activation and brown adipose tissue (BAT) thermogenic regulation through modulating the anti-microbial peptides (AMPs)-controlled gut microbiota and their metabolites. We also identified the new AMPK-mediated mechanism of intestine-BAT communication that may partially underlie the effects of metformin in metabolic diseases. Our current study discovered that another nutrient sensor mTOR crosstalk with white adipose tissue (WAT) browning regulates glucose homeostasis and energy metabolism. We observed significantly enhanced WAT browning and glucose homeostasis in intestinal epithelium-specific mTOR knockout (mTOR-IKO) mice compared to mTORfl/fl mice. Moreover, the gut microbiota profile of mTOR-IKO mice was markedly shifted compared to that of mTORfl/fl mice. Similarly, we identified significant differences in the serum and fecal levels of some bacterial metabolites in mTOR-IKO mice. Furthermore, we observed enhanced WAT browning and glucose homeostasis in WT mice after fecal microbiota transplantation from mTOR-IKO mice. Mechanistically, we found that the expression of various AMPs, including REG3 and RELMb were significantly lower in the intestines of mTOR-IKO mice compared to controls. These results indicate that intestinal mTOR remotely controls WAT browning through a mTOR-AMPs-microbiome-WAT axis. Determining the role of intestinal AMPK/mTOR-AMPs pathways in energy and metabolism will help fill the gap in our current understanding of how the intestine serves as an important site of AMPK/mTOR action in metabolic regulation.

Disclosure
E. Zhang: None. W. Huang: None.
2047-LB: METTL2 Knockout Mitigates Obesity and Metabolic Disorders Induced by High-Fat Diet
Authors: HE SUNYUE , NAN WU , ZHAO YUCHEN , LU LUSI , LIN XIHUA , ZHANG WENJING , ZHOU JIAQIANG 
Published: June 2024

Objective: METTL2 is a tRNA methyltransferase primarily accountable for m3C modification of cytoplasmic tRNA. However, the existing comprehension of METTL2 is relatively limited, and the association between METTL2 and metabolic diseases remains undisclosed. This study aims to investigate the role of METTL2 in glucose-lipid metabolism and elucidate its underlying mechanism.
Methods: Studies were conducted in age-matched male METTL2 whole-body knockout (MeKO) and wild-type (WT) mice that fed normal chow (NC) or a high-fat diet (HFD) for 20 weeks. We performed comprehensive longitudinal assessment of body weight, energy balance, glucose homeostasis and global fat deposition. Additionally, we assessed steatohepatitis, adipose hypertrophy and adipose inflammation, and further explored potential mechanism.
Results: In the basal state, MeKO mice exhibited slower weight gain and body length compared to WT mice, although there was no significant difference in glucose homeostasis. In HFD-induced obesity model, MeKO mice showed reduced body weight and fat mass compared to WT mice. This reduction was accompanied by increased energy expenditure, while food intake remained unchanged. As a result, metabolic homeostasis was significantly improved in MeKO mice. METTL2 knockout alleviated the progression of steatohepatitis by inhibiting hepatic fatty acid uptake and synthesis. Furthermore, METTL2 knockout upregulated the expression of the lipolysis molecule ATGL in epididymal white adipose tissue and ameliorated adipose tissue inflammation.
Conclusion: Taken together, these findings suggested that METTL2 represents a novel molecule involved in HFD-induced obesity and associated metabolic disorders.

Disclosure
S. He: None. W. Nan: None. Y. Zhao: None. L. Lu: None. X. Lin: None. W. Zhang: None. J. Zhou: None.

Funding
National Natural Science Foundation of China (grant number: 82270857)
2049-LB: Robust Single Nucleus RNA Sequencing Reveals Depot-Specific Cell Population Dynamics in Adipose Tissue Remodeling during Obesity
Authors: SO JISUN , CHEOL ROH HYUN 
Published: June 2024

Single nucleus RNA sequencing (snRNA-seq) has emerged as an alternative approach to address the inherent limitations of single cell RNA sequencing (scRNA-seq). However, snRNA-seq encounters technical challenges in obtaining high-quality nuclei and RNA, which persistently hinder its applications. Here, we present a robust technique for isolating nuclei that effectively overcomes these challenges across various tissue types. Our method demonstrates a marked enhancement in the quality of snRNA-seq data, surpassing that of previously reported datasets. Employing this approach, we comprehensively characterize the cellular dynamics underlying adipose tissue remodeling during obesity. Various cell types within adipose tissue display substantial responses to obesity, with significant variations observed depending on fat depots. Through the integration of nuclear RNA-seq data acquired from adipocyte nuclei of different sizes, we identify multiple adipocyte subpopulations that can be categorized by size and functionality. Specifically, we characterize dysfunctional hypertrophic adipocytes prevalent in visceral adipose tissues during obesity, exhibiting hallmark features such as cellular stress, inflammation, and impaired gene expression. The adipocyte subpopulations contribute differentially to a range of biological pathways involved in the pathophysiology of adipose tissue during obesity. Collectively, our study establishes a robust snRNA-seq method that offers novel insights into the mechanisms orchestrating adipose tissue remodeling during obesity, with broader applicability extending to diverse biological systems.

Disclosure
J. So: None. H. Roh: None.

Funding
American Diabetes Association (7-21-JDF-056); National Institute of Diabetes and Digestive and Kidney Diseases (R01DK129289)
2050-LB: The Effect of Pharmacological Activation of Liver X Receptor (LXR) in the Heart of Obese Mice
Authors: ALFARQANI YOUSUF , OLICHWIER ADAM J. , YOUNG JAMEY , BEDNARSKI TOMASZ 
Published: June 2024

Even though fatty acids (FAs) are the main source of energy for cardiomyocytes, in pathological conditions heart shifts its metabolism toward increased glucose reliance, which leads to excess accumulation of FAs in the form of triglycerides (TGs) and cardiac dysfunction. Therefore, we have investigated the role of liver X receptor (LXR), a nuclear receptor that regulates lipid and glucose homeostasis, in cardiac muscle during progressive obesity. As a model we used 8-week-old, male, hyperphagic MC4R knockout mice (MC4RKO), and wildtype C57BL/6J mice (WT) as a control, placed on either standard laboratory diet (Chow) or high-fat, high-fructose, high-cholesterol western diet (WD) for additional 8 weeks. Some of the WD-fed mice had their food supplemented with LXR activator, GW3965. LXR activation significantly decreased whole body and fat mass in both WT and MC4RKO mice which was accompanied by improved glucose tolerance and insulin sensitivity as indicated by glucose tolerance test and HOMA-IR score. LXR activation significantly upregulated plasma free FAs content in WT animals, decreased plasma TGs level in MC4RKO mice, and did not affect plasma cholesterol. We therefore investigated if plasma lipids changes affected cardiac metabolism. Interestingly, LXR activation significantly decreased expression of lipogenic factors, such as sterol regulatory element-binding transcription factor 1 (Srebpf1), lysophosphatidylcholine acyltransferase 1 (Lpcat1), fatty acid synthase (Fasn), when compared to WD-fed WT and MC4RKO mice. Interestingly, those changes were correlated with downregulated expression of endoplasmic reticulum stress marker, activating transcription factor 6 (Atf6) and fibrotic marker, expression of collagen 1 (Col1). Summarizing, normalization of lipid metabolism by LXR activation may have protective effect on during obesity by mitigating lipogenesis.

Disclosure
Y. Alfarqani: None. J. Young: Research Support; Merck Sharp & Dohme Corp. Consultant; Metalytics. Stock/Shareholder; Eli Lilly and Company. T. Bednarski: None.
2051-LB: Rhein Targets Macrophage SIRT2 to Promote Adipose Tissue Thermogenesis in Obesity
Authors: ZHOU RUONAN , ZHU ZIWEI , XU PINGYUAN , SHEN LIXUAN , WANG ZIWEI , XUE YINGYING , XIANG YINGYING , CAO YUE , YU XIZHONG , YU JIN , ZHAO JUAN , YAN JING , YANG QIN , FANG PENGHUA , SHANG WENBIN 
Published: June 2024

Introduction & Objective: Rhein, a component derived from rhubarb as well as the active metabolite of the anti-osteoarthritis drug diacerein, has been proven to possess strong anti-inflammatory properties. However, the exact mechanism underlying the anti-inflammatory effects of rhein, and the role of rhein in ameliorating obesity remains unclear.
Methods: Diet induced obese (DIO) mice were employed to observe the effects of rhein on metabolism. A macrophage-adipocyte co-culture system was constructed to elucidate the exact mechanism underlying the beneficial effect of rhein on metabolism. Acetylome analysis was performed to screen the acetylation-modifying enzymes regulated by rhein. Surface plasmon resonance assay was used to verify the interaction between rhein and SIRT2. Lyz2-iCre mice injected with rAAV-DIO-shSirt2 were used to verify the durg target of rhein in vivo. PBMCs from patients with obesity receiving diacerein or placebo treatment were collected for acetylation assay.
Results: Rhein mitigated obesity by promoting white adipose tissue thermogenesis in DIO mice, and rhein promoted adipocyte thermogenesis through inhibiting the activation of NLRP3 inflammasome in macrophages. Further study proved that rhein directly interacts with SIRT2 and inhibits NLRP3 inflammasome activation in a SIRT2-dependent way. Myeloid knockdown of Sirt2 abrogated the metabolic benefits induced by rhein in DIO mice. PBMCs from patients with obesity receiving diacerein treatment had significant lower level of acetylation than those from the placebo group.
Conclusion: Rhein promotes adipose tissue thermogenesis by targeting SIRT2 to regulate acetylation-mediated NLRP3 inflammasome activation in macrophages during obesity. Rhein and its derivatives may become potential drug for treating obesity.

Disclosure
R. Zhou: None. Z. Zhu: None. P. Xu: None. L. Shen: None. Z. Wang: None. Y. Xue: None. Y. Xiang: None. Y. Cao: None. X. Yu: None. J. Yu: None. J. Zhao: None. J. Yan: None. Q. Yang: None. P. Fang: None. W. Shang: None.

Funding
National Natural Science Foundation of China (81873060, 81473391 and 82374100); Priority Academic Program Development of Jiangsu Higher Education Institutions (ZYX03KF058); Graduate Research and Innovation Projects of Jiangsu Province (KYCX23_2133 and SJCX23_0728).
2069-LB: ANGPTL7 Promotes Oxidative Stress and Inflammatory Response in HepG2 Cells via Targeting the STAT3-iNOS, COX-2 Signaling Pathway
Authors: GAO QIAN , ZHOU YARU , LIU YAN , LI MIN , GAO MINGMING 
Published: June 2024

Objective: Elevated hepatocyte oxidative stress and inflammation may trigger lipid accumulation and promote the formation of NAFLD. As a new member of the ANGPTL family, ANGPTL7 plays an important role in inflammatory responses, angiogenesis and oxidative stress. However, whether ANGPTL7 participates in the pathogenesis of NAFLD still remains unknown. Therefore, in this study, we investigated the role of ANGPTL7 in HepG2 cells.
Methods: HepG2 cells were divided into control group (pcDNA3.1(+)), ANGPTL7 overexpression group (Angptl 7 OE ) and ANGPTL7 overexpression group with STAT3 knockdown group (Angptl 7 OE + si-STAT3). Cell viability was assessed by CCK-8 assay. Cell lipid level was checked by oil red O staining. Cellar IL-6, TNF-α, ROS, MDA, SOD and GSH level were determined by kits. The expression of ANGPTL7, STAT3, iNOS and COX-2 were measured by RT-PCR and western blot.
Results: Compared with CON group, ANGPTL7 overexpression led to elevated cellular IL-6, TNF-α, ROS and MDA, and reduced GSH and SOD, and increased expression of STAT3, iNOS and COX-2, indicating promoted oxidative stress and inflammatory responses. All these alterations caused by ANGPTL7 can be partly reversed by STAT3 knockdown.
Conclusion: Angptl7 could cause oxidative stress and inflammatory response partly via activating STAT3 in HepG2 cells.

Disclosure
Q. Gao: None. Y. Zhou: None. Y. Liu: None. M. Li: None. M. Gao: None.
207-OR: Food Insecurity Patterns and Mental Health among Youth and Young Adults with Diabetes
Authors: ALFALKI ALI M. , JULCEUS EMMANUEL F. , FLORY KATE , MENDOZA JASON A. , MALIK FAISAL , FRONGILLO EDWARD A. , REBOUSSIN BETH A. , BELLATORRE ANNA , DABELEA DANA , PIHOKER CATHERINE , LIESE ANGELA D. 
Published: June 2024

Introduction & Objective: We explored the associations of food insecurity (FI) patterns with symptoms of depression, anxiety, stress, and changes therein in youth and young adults (YYA) with type 1 (T1D) and type 2 diabetes (T2D).
Methods: Longitudinal data (2016-2022) from 747 YYA with T1D and 97 with T2D were analyzed using multivariable linear regression. Food security was ascertained with the Household Food Security Survey Module at 3 times (t1, t2, and t3) and patterned as persistently food secure (PFS), persistently food insecure (PFI), and intermittently food insecure (IFI). Mental health at t3 and changes from t2 to t3 were characterized with the Center for Epidemiologic Studies Depression Scale, the Generalized Anxiety Disorder Scale, and Cohen’s Perceived Stress Scale; higher scores indicated greater severity.
Result: Among YYA with T1D, 6.6% experienced PFI and 20.3% IFI; among YYA with T2D, 16.5% were PFI and 42.3% IFI. In T1D, PFI and IFI were associated with greater depressive, anxiety, and stress symptoms at t3 but not with changes. In T2D, PFI was associated with greater depressive symptoms at t3 but not with symptom changes.
Conclusion: Both persistent and intermittent patterns of FI were associated with mental health symptoms, more so for those with PFI, underscoring the critical interplay between FI and mental health symptoms in YYA with diabetes.

Disclosure
A.M. Alfalki: None. E.F. Julceus: None. K. Flory: None. J.A. Mendoza: None. F. Malik: None. E.A. Frongillo: None. B.A. Reboussin: None. A. Bellatorre: None. D. Dabelea: None. C. Pihoker: None. A.D. Liese: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (R01DK117461)
2073-LB: Unveiling the Hidden—Insulin Resistance and Cardiometabolic Risks in Overweight Adolescents
Authors: CHHABRA SAHIL , CHHABRA SARAH , PATIL RANJIT , ARORA SAHIBA , CHHABRA NAMRATA 
Published: June 2024

Introduction and Objectives: Adolescent obesity escalates cardiometabolic complications and insulin resistance (IR). While adult IR criteria are clear, their adaptation for adolescents is inconsistent due to standardization challenges. The study aimed to determine the prevalence of insulin resistance and its association with anthropometric measurements, cutaneous indicators, and specific biochemical parameters in overweight and obese adolescents.
Methods: A cross-sectional study was conducted encompassing 182 adolescents aged 10-19. Participants underwent comprehensive assessments, including physical examinations, questionnaires, and biochemical tests.
Results: The study divided participants into normal-weight, overweight, and obese groups. It found high rates of central obesity, hypertension, and hyperglycemia, especially among obese participants. The mean HOMA-IR value stood at 3.5, with 62.6% of participants displaying insulin resistance, more common in males (66.6%) than females (58.6%). Pubertal individuals showed a higher incidence (82.2%). Signs suggesting non-alcoholic fatty liver disease were prominent in overweight and obese groups. In total, 13.18% had metabolic syndrome, with varying degrees of its components present in others.IR was also linked with sleep disturbances, low physical activity, and excessive screen time.
Conclusion: Our study unveiled critical surrogate markers for IR in overweight and obese adolescents. Comprehensive clinical assessments, prompt lifestyle changes, and therapeutic measures are essential in addressing IR and related conditions. Recognizing and responding to these markers early could be fundamental for mitigating associated health risks and optimizing clinical management strategies for overweight and obese adolescents.
Keywords Obesity; Insulin resistance; Adolescence; Dyslipidemia, and Metabolic syndrome

Disclosure
S. Chhabra: None. S. Chhabra: None. R. Patil: None. S. Arora: None. N. Chhabra: None.
2079-LB: Sociodemographic Profile and Obesity—An Indian Perspective
Authors: DESHPANDE NEETA , SINGH NAGENDRA K. , PARIKH RAKESH M. , SAHAY RAKESH K. , AGARWAL SANJAY , KAPOOR NITIN , MAKKAR BRIJ , SREENIVASA MURTHY L. 
Published: June 2024

Introduction & Objective: Diverse sociodemographic profiles play a pivotal role in shaping health behaviours. This survey presents the lifestyle habits and health profiles among different socio-economic populations in India.
Methods: A pan-Indian survey using social media and awareness camps, collected demographics, BMI, and health history. responses on BMI perception, lifestyle practices, and obesity awareness. Participants were categorized by residence, education, and occupation.
Results: In a survey of 60,327 individuals with a male-to-female ratio of 1.9, 65% in the age group of 30-60 years (M:F), ~79% from urban/semi-urban areas, 63% were employed (78.4% M). Majority of the students (76.6%) and employed (56.8%) had at least a bachelor’s degree. No schooling was the highest among unemployed (22%) and homemakers (16%). Obesity was higher among home makers (70%) and lowest among students (42%); diabetes, hypertension, high cholesterol was highest among the retired (70.1%, 59.9%, 32.5%), followed by homemakers (67.7%, 45.5%, 25.8%). BMI distribution (overweight, obese) was (44.7%, 3.1%) in rural; (42.2%, 2.8%) in semi-urban and (45.2%, 2.1%) in urban. Longer screen times were in urban [weekdays (3.3% &gt; 10h, 15.1 6-10h) and weekends (3.0% &gt;10h, 16.5% 6-10h)] and students [weekdays (5.9% &gt;10h; 17.6% 6-10h) and weekends (5.6% &gt;10h; 26.5% 6-10h)]. Similarly, for order-in frequency, urban dwellers had at least one meal per week (76.1%) and students (82%) had at least one meal per week and 25% had more than two meals per week. Urban dwellers (57.3%), Students (60%) and employed (58%) individuals liked to exercise for at least 30 min a day. Obesity prevalence remained comparable across education levels (~64-68%), with weight loss efforts and willingness to receive weight loss information increasing with higher education (master’s degree ~35%).
Conclusion: Lifestyle, wellness, and management varies across diverse sociodemographic groups in India.

Disclosure
N. Deshpande: None. R.M. Parikh: None. R.K. Sahay: Speaker's Bureau; Novo Nordisk, Sun Pharmaceutical Industries Ltd., USV Private Limited, Eris Lifesciences Ltd. S. Agarwal: None. N. Kapoor: None. B. Makkar: None. L. Murthy: None.
2096-LB: Mitochondrial DNA Integrity Is Required for ß-Cell Health In Vivo
Authors: DAVIDSON REBECCA K. , ZHU JIE , RECK EMMA C. , SOLEIMANPOUR SCOTT 
Published: June 2024

Type 2 diabetes (T2D) is a metainflammatory disease characterized by impairments in mitochondrial function and ultrastructure that contribute to the overall disruption of β-cell function. Mitochondria rely on both the nuclear genome as well as their own 16.6 kilobase-pair circular genome to generate the machinery required for oxidative phosphorylation (OXPHOS). Recently, our group identified a reduction in mitochondrial DNA (mtDNA) copy number in islets from donors with T2D, indicating a disruption in mitochondrial genome stability. While mtDNA genome instability is implicated in several diseases, its impact on β-cell dysfunction in diabetes has yet to be explored. Here, we generated a mouse model prone to increased β-cell mtDNA deletions by selective expression of a dominant negative Twinkle (TwnkK320E) helicase mutant, which is essential for mtDNA maintenance. Beginning at 5 weeks, β-TwnkK320E mice exhibited impaired glucose tolerance, which progressively worsened with age. Circulating insulin concentrations following glucose stimulation were also reduced in β-TwnkK320E mice by 5 weeks of age, yet there was no difference in β-cell mass, suggestive of a β cell functional defect. Further, we observed a complete loss of MafA, a key regulator of β-cell maturity, from a subset of β cells in β-TwnkK320E mice. While mitochondrial mass was unchanged between groups, β‑TwnkK320E islets have altered expression of subunits of all OXPHOS complexes, as well as reduced glucose-stimulated oxygen consumption, indicative of impaired mitochondrial function. Together, these data suggest that the accumulation of mtDNA deletions diminishes β-cell function and support the importance of mitochondrial genome integrity to β-cell health.

Disclosure
R.K. Davidson: Employee; Eli Lilly and Company. J. Zhu: None. E.C. Reck: None. S. Soleimanpour: Advisory Panel; Novo Nordisk. Research Support; Ono Pharmaceutical Co., Ltd.

Funding
National Institutes of Health (T32DK101357)