Adipose Tissue Distribution Research Articles

Contribution of Sex Differences to Development of Cardiovascular Disease in Metabolic-Associated Steatotic Liver Disease (MASLD)

Sex differences are a complex and crucial variable in developing and progressing metabolic and cardiovascular disease pathophysiology and clinical outcomes. The female sex, compared to the male sex, is protected from metabolic disturbances and their resulting cardiovascular events. However, the peculiar life phases associated with females, such as puberty, pregnancy, and premenopausal and menopausal stages, are all associated with different risks for the development of cardiovascular disease (CVD). Metabolic dysfunction-associated steatotic liver disease (MASLD), a condition of hepatic steatosis, and at least one feature of metabolic syndrome is associated with an increased risk of cardiovascular events. The risk of MASLD and its progression to the development of CVD differs between men and women. Differences in several factors, including formyl peptide receptor (FPR) 2, adipose tissue distribution, liver pyruvate kinase (LPK), and ketone body production, may underlie the sex differences in the risk of development of MASLD-induced CVD. Understanding the specific risk factors involved in the development and progression of MASLD between the sexes is crucial. This knowledge will provide important insights into the mechanisms responsible for its cardiovascular complications and can potentially lead to therapeutics targeted explicitly for each sex, offering new hope in the fight against MASLD-induced CVD.

Interactions between glucagon like peptide 1 (GLP-1) and estrogens regulates lipid metabolism

Obesity, characterized by excessive fat accumulation in white adipose tissue (WAT), is linked to numerous health issues, including insulin resistance (IR), and type 2 diabetes mellitus (DM2). The distribution of adipose tissue differs by sex, with men typically exhibiting android adiposity and pre-menopausal women displaying gynecoid adiposity. After menopause, women have an increased risk of developing android-type obesity, IR, and DM2. Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) are important in treating obesity and DM2 by regulating insulin secretion, impacting glucose and lipid metabolism. GLP-1Rs are found in various tissues including the pancreas, brain, and adipose tissue. Studies suggest GLP-1RAs and estrogen replacement therapies have similar effects on tissues like the liver, central nervous system, and WAT, probably by converging pathways involving protein kinasesTo investigate these interactions, female rats underwent ovariectomy (OVR) to promote a state of estrogen deficiency. After 20 days, the rats were euthanized and the tissues were incubated with 10 μM of liraglutide, a GLP-1RA. Results showed significant changes in metabolic parameters: OVR increased lipid catabolism in perirenal WAT and basal lipolysis in subcutaneous WAT, while liraglutide treatment enhanced stimulated lipolysis in subcutaneous WAT. Liver responses included increased stimulated lipolysis with liraglutide. Transcriptome analysis revealed distinct gene expression patterns in WAT of OVR rats and those treated with GLP-1RA, highlighting pathways related to lipid and glucose metabolism. Functional enrichment analysis showed estrogen’s pivotal role in these pathways, influencing genes involved in lipid metabolism regulation.Overall, the study underscores GLP-1RA acting directly on adipose tissues and highlights the complex interactions between GLP-1 and estrogen in regulating metabolism, suggesting potential synergistic therapeutic effects in treating metabolic disorders like obesity and DM2.

Alterations in Adipose Tissue and Adipokines in Heterozygous APE1/Ref-1 Deficient Mice.

The role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in adipose tissue remains poorly understood. This study investigates adipose tissue dysfunction in heterozygous APE1/Ref-1 deficiency (APE1/Ref-1+/-) mice, focusing on changes in adipocyte physiology, oxidative stress, adipokine regulation, and adipose tissue distribution. APE1/Ref-1 mRNA and protein levels in white adipose tissue (WAT) were measured in APE1/Ref-1+/- mice, compared to their wild-type (APE1/Ref-1+/+) controls. Oxidative stress was assessed by evaluating reactive oxygen species (ROS) levels. Histological and immunohistochemical analyses were conducted to observe adipocyte size and macrophage infiltration of WAT. Adipokine expression was measured, and micro-magnetic resonance imaging (MRI) was used to quantify abdominal fat volumes. APE1/Ref-1+/- mice exhibited significant reductions in APE1/Ref-1 mRNA and protein levels in WAT and liver tissue. These mice also showed elevated ROS levels, suggesting a regulatory role for APE1/Ref-1 in oxidative stress in WAT and liver. Histological and immunohistochemical analyses revealed hypertrophic adipocytes and macrophage infiltration in WAT, while Oil Red O staining demonstrated enhanced ectopic fat deposition in the liver of APE1/Ref-1+/- mice. These mice also displayed altered adipokine expression, with decreased adiponectin and increased leptin levels in the WAT, along with corresponding alterations in plasma levels. Despite no significant changes in overall body weight, microMRI assessments demonstrated a significant increase in visceral and subcutaneous abdominal fat volumes in APE1/Ref-1+/- mice. APE1/Ref-1 is crucial in adipokine regulation and mitigating oxidative stress. These findings suggest its involvement in adipose tissue dysfunction, highlighting its potential impact on abdominal fat distribution and its implications for obesity and oxidative stress-related conditions.

Abstract 4147644: Regional Distribution and Overlap of Left Atrial Epicardial Adipose Tissue and Fibrosis

Background: Left atrial epicardial adipose tissue (LA-EAT) and fibrosis are implicated in the pathophysiology of the atrial fibrillation (AF) substrate. Hypothesis: The distribution of fibrosis and LA-EAT differs across various regions of the LA. Aims: Ascertain whether high fibrosis regions coincide with high EAT regions. Identify specific anatomical regions in which LA-EAT and fibrosis tend to co-localize. Methods: LA-EAT was imaged using MRI Dixon sequences and images were segmented axially using the software contouring tools. LGE-MRI was used for LA fibrosis quantification and segmentation. The regions of fibrosis and fat were then co-registered with the atrial geometry and projected onto the left atrial shell. A universal atrial coordinates (UAC) approach was then used to systematically delineate anatomical LA regions in a manner independent of inter-individual variabilities in scale and shape. Specifically, the LA was divided into 10 regions (left and right versions of: posterior-inferior, posterior-superior, roof, anterior-superior, and anterior-inferior). Levene’s test and ANOVA were used to check for any statistically significant variability. Results: Nineteen patients were recruited (94% male; median age 72[62-74]; BMI 32.1±6.3; LA volume index 71.0±21.5mL/m 2 ).LA fibrosis was highest in the left posterior superior segment, right anterior inferior, and left posterior inferior (39.3±16.2%,34.7±26.8%, and 25.7±20.9% respectively;F=1.9,p=0.15). LA-EAT was most prominent in the right anterior superior, left posterior inferior, and left anterior inferior segments (38.1±25.3%,35.6±18.4%,and 33.1±18.9% respectively; F=0.94, p= 0.39). Spatial co-localization of fat and fibrosis was highest in the left posterior inferior region (8.95±2.1%), followed by the left posterior superior, right anterior superior, and left anterior inferior region (7.9±2.1%,7.2±1.7%,and 6.3±1.6% respectively; F= 0.29, p=0.83 ). Conclusion: LA fibrosis and EAT have differing regional preponderances, impacting the AF substrate through infiltrative and paracrine effects. This fibro-fatty remodeling creates structural and conduction abnormalities, forming stable reentrant circuits and perpetuating AF by providing varied pathways and refractory periods.

Relationship between Cardiometabolic index and endometriosis in a US nationally representative sample: results from NHANES 1999-2006.

Endometriosis is an estrogen-dependent gynecological endocrine condition and a systemic inflammatory disease associated to improper lipid metabolism and increased cardiovascular risk. The Cardiometabolic Index (CMI) is a novel indicator representing visceral adipose tissue distribution and metabolic dysfunction, integrating lipid metabolism indicators and the waist-to-height ratio. While anomalies in lipid metabolism are often associated with (BMI) Body Mass Index, literature consistently shows a negative link between endometriosis and female BMI, and some studies have found that endometriosis is one of the few reproductive diseases not persistently positively correlated with obesity. Given the limitations of BMI, a comprehensive index like CMI is crucial for exploring the incidence of endometriosis. Currently, research on the correlation between CMI and endometriosis is lacking, prompting this study to investigate this association. To investigate the association between the CMI and the risk of having endometriosis in a sample representing the entire U.S. population. A cross-sectional analysis was conducted using data from four cycles of the National Health and Nutrition Examination Survey (NHANES) spanning the years 1999 to 2006. The study included individuals aged 20 to 54 with a documented history of endometriosis and complete CMI data. Logistic regression analysis, subgroup and interaction analyses, smooth curve fitting, and restricted cubic splines (RCS) were utilized to examine the association between CMI and endometriosis. The study found that individuals with higher CMI had an increased probability of developing endometriosis. This relationship remained significant after adjusting for potential confounders such as age, ethnicity, Poverty Income Ratio (PIR), drinking, smoking, education level, and marital status. The fully adjusted model revealed a positive correlation between CMI and endometriosis (OR = 1.21; 95% CI, 1.04-1.40, p < 0.05). Subgroup and interaction analyses showed no significant effect modification by age, BMI, PIR, hypertension, drinking, smoking, or menarche age (all p-values for interaction > 0.05). Our study shows a link between CMI and the chance of getting endometriosis.Due to the common occurrence of endometriosis and the lack of clarity surrounding their cause, more study is needed to confirm our results and find out if CMI could be used as a warning sign for endometriosis.

Adipose Tissue-Resident Sphingomonas Paucimobilis Suppresses Adaptive Thermogenesis by Reducing 15-HETE Production and Inhibiting AMPK Pathway.

Obesity represents a low-grade chronic inflammation status, which is associated with compromised adaptive thermogenesis. However, the mechanisms underlying the defective activation of thermogenesis in chronic inflammation remain unclear. Here, a chronic inflammatory model is first estabolished by injecting mice with low-dose lipopolysaccharide (LPS) before cold exposure, and then it is verified that LPS treatment can decrease the core body temperature of mice and alter the microbial distribution in epididymal white adipose tissue (eWAT). An adipose tissue-resident bacterium Sphingomonas paucimobilis is identified as a potential inhibitor on the activation of brown fat and browning of inguinal WAT, resulting in defective adaptive thermogenesis. Mechanically, LPS and S. paucimobilis inhibit the production and release of 15-HETE by suppressing its main metabolic enzyme 12 lipoxygenase (12-LOX) and 15- Hydroxyeicosatetraenoic acid (15-HETE) rescues the impaired thermogenesis. Interestingly, 15-HETE directly binds to AMP-activated protein kinase α (AMPKα) and elevates the phosphorylation of AMPK, leading to the activation of uncoupling protein 1 (UCP1) and mitochondrial oxidative phosphorylation (OXPHOS) complexes. Further analysis with human obesity subjects reveals that individuals with high body mass index displayed lower 15-HETE levels. Taken together, this work improves the understanding of how chronic inflammation impairs adaptive thermogenesis and provides novel targets for alleviating obesity.

Fructose restriction has beneficial effects on adipose tissue distribution but not on serum adipokine levels: Post-hoc analysis of a double-blind randomized controlled trial.

We aimed to examine the effects of isocaloric fructose restriction on adipose tissue distribution and serum adipokines. Individuals with BMI >28 kg/m2 (n = 44) followed a 6-week fructose-restricted diet and were randomly allocated to (double-blind) oral supplementation with fructose (control) or glucose (intervention) powder three times daily. Visceral (VAT) and subcutaneous (SAT) adipose tissue was quantified with MRI. Serum interleukin 6 and 8, tumour necrosis factor alpha and adiponectin levels were measured with sandwich immunoassay. BMI decreased in both groups, but the change did not differ between groups (-0.1 kg/m2, 95%CI: -0.3; 0.5). SAT decreased statistically significantly in the control group (-23.2 cm3, 95%CI: -49.4; -4.1), but not in the intervention group. The change in SAT did not differ between groups (29.6 cm3, 95%CI: -1.2; 61.8). No significant differences in VAT were observed within or between study arms. The VAT/SAT ratio decreased statistically significantly in the intervention group (-0.02, 95%CI: -0.04; -0.003) and the change was significantly different between groups (-0.03, 95%CI: -0.54; -0.003). Serum adipokine levels were not affected by the intervention. This study shows that a fructose-restricted diet resulted in a favourable change in adipose tissue distribution, but did not affect serum adipokines. Further studies are warranted to clarify the underlying mechanisms how fructose affects adipose tissue distribution.

The distribution and mass index of epicardial adipose tissue were correlated with microvascular obstruction formation in patients with ST-segment elevation myocardial infarction

Abstract Introduction Epicardial adipose tissue (EAT), refers to a metabolically active fat depot between the visceral pericardium and the outer margin of the myocardium. EAT has gradually emerged as a novel target for risk stratification of coronary artery disease due to its distinctive location and multifaceted metabolic properties. Microvascular obstruction (MVO) after primary percutaneous coronary intervention (pPCI) is identified as an independent risk factor for poor prognosis in patients with acute myocardial infarction. However, the clinical implications of EAT in MVO formation in patients with ST-segment elevation myocardial infarction (STEMI) remain unclear. Recently, cardiac magnetic resonance (CMR) has emerged as the gold standard technique to detect the extent of MVO and evaluate EAT parameters. Purpose This study aimed to evaluate the correlation between EAT accumulation and MVO occurrence detected by CMR in STEMI patients. Methods A total of 129 STEMI patients who underwent pPCI successfully were enrolled. Clinical characteristics including demographic characteristics, cardiovascular risk factors, laboratory data and angiographic parameters were recorded from each patient by 1 trained physician. All patients underwent CMR within 1 week following pPCI to evaluate infarct size, MVO volume and EAT distribution. All CMR data were transferred to Q-MASS MR 8.1 imaging system (Medis, Leiden, The Netherlands) and interpreted twice by 2 expert radiologists who were blinded to the angiographic and clinical data of patients. Results Compared to STEMI patients without MVO, STEMI patients with MVO presented with higher peak troponin T levels, increase of neutrophil lymphocyte ratio (NLR) and C-reactive protein (CRP), larger infarct size and compromised left ventricular ejection fraction. Total EAT volume, EAT mass index, left atrioventricular EAT volume, left atrioventricular EAT mass index and thickness of EAT in the left atrioventricular groove were unanimously associated with the occurrence of MVO. The left atrioventricular EAT mass index in STEMI patients with MVO were significantly larger than that in STEMI patients without MVO (24.72±5.049 g/m2 vs 18.63±3.670 g/m2, P&amp;lt;0.001). Multivariate logistic regression analysis demonstrated that NLR, peak troponin T levels and left atrioventricular EAT mass index were independent predictors of MVO. LV EAT mass index showed a robust and independent relationship with MVO formation and a cutoff value &amp;gt;21.5192 g/m2 predicted the presence of MVO with a sensitivity and specificity of 79.5% and 80.4%, respectively. Conclusions Left atrioventricular EAT mass index is an independent predictor of MVO. Measurement of EAT using CMR could be used for risk stratification and might be a promising target in developing new therapies to reduce myocardial reperfusion injury in patients with STEMI.

Cardiometabolic index and the risk of new-onset chronic diseases: results of a national prospective longitudinal study.

The cardiometabolic index (CMI) has emerged as a novel marker for evaluating the distribution and dysfunction of visceral adipose tissue, yet its correlation with numerous diseases, particularly new-onset chronic conditions, remains underexplored. Therefore, we aim to explore the association of cardiometabolic index (CMI) and new-onset chronic diseases. The analysis utilized data from the China Health and Retirement Longitudinal Study, with a baseline in 2011 and follow-ups biennially until 2020. Fourteen new-onset chronic diseases were diagnosed based on self-report, and separate cohorts were created for each disease. CMI was calculated as triglycerides/high-density lipoprotein cholesterol multiplied by the waist-to-height ratio. Cox proportional hazards models were used to assess the association between CMI and new-onset chronic diseases, while restricted cubic spline (RCS) models were employed to explore potential nonlinear effects. Additional and sensitivity analyses included Kaplan-Meier survival curves, subgroup analyses, multiple imputations, and exclude outcome events at the first follow-up. Higher levels of CMI were associated with an increased risk of new-onset hypertension (HR=1.05, 95% CI=1.04-1.06, P<0.001), diabetes (HR=1.08, 95% CI=1.06-1.09, P<0.001), dyslipidemia (HR=1.07, 95% CI=1.06-1.09, P<0.001), liver disease (HR=1.05, 95% CI=1.03-1.07, P<0.003), and stroke (HR=1.04, 95% CI=1.02-1.06, P<0.001), although the association with stroke was not significant after adjusting for confounders (HR=1.02, 95% CI=1.00-1.05, P=0.054). Participants in the highest quartile of CMI had a significantly higher risk of these diseases compared to those in the lowest quartile. RCS analyses showed a significant nonlinear relationship between CMI and the risk of these diseases above. CMI showed a significant positive association with the risk of new-onset chronic diseases such as hypertension, diabetes, dyslipidemia, and liver disease. Future applications of CMI hold promise as an effective marker for early identification of chronic disease risk.

Evaluation of Health Associations With Height-Normalised Abdominal Body Composition Indices: A Single-Centre Cross-Sectional Study.

Traditional metrics such as body mass index (BMI) and waist circumference (WC) fail to accurately assess the health outcomes associated with abdominal adiposity, because they neglect the intricacies of adipose tissue distribution. Notably, the variability in body composition scaled to height remains underexplored in Chinese demographics. This study introduces height-normalised indices of abdominal adiposity using computed tomography (CT) scans and further assesses their associations with various health outcomes. In a large, diverse Chinese population (n = 1054 healthy individuals; n = 1159 with dyslipidemia; n = 803 with diabetes; n = 1289 with cardio-cerebrovascular diseases; n = 1108 with cancers; and n = 509 with abnormal bone mas), abdominal CT scans were performed and allometric growth model analyses were used to derive height-normalised indices (body composition/heightβ). Logistic regression models assessed the associations between these indices and health outcomes. Distinct scaling powers were observed for visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and total abdominal adipose tissue (TAT), as well as for sagittal diameter (SAD), with marked sex differences. Powers for VAT were 1.786 ± 1.270 for males and 1.274 ± 0.692 for females. Powers for SAT were 2.266 ± 0.856 for males and 1.656 ± 0.497 for females. Powers for TAT were 2.141 ± 0.967 for males and 1.438 ± 0.489 for females. Powers for SAD were 0.646 ± 0.217 for males and 0.678 ± 0.141 for females. After controlling for age, BMI and WC, VAT/heightβ, TAT/heightβ and SAD/heightβ retained their significantly positive associations with the odds of health outcomes, whereas SAT/heightβ did not. Our findings endorse the clinical utility of height-normalised indices, particularly VAT/heightβ, TAT/heightβ and SAD/heightβ, in health outcomes assessment. These indices, grounded in robust empirical data, underscore the necessity of a nuanced approach in obesity-related health evaluations, advocating for a departure from conventional methods like BMI.

7654 Unusual Case of Lipodystrophy: A Novel Disease Phenotype?

Abstract Disclosure: M. Celik Guler: None. E.D. Frontera: None. K. Hoose: None. M.C. Foss de Freitas: Advisory Board Member; Self; PTC Therapeutics. Speaker; Self; Amryt. L. Douyon: None. E.A. Oral: Advisory Board Member; Self; Amryt, Regeneron Pharmaceuticals. Consulting Fee; Self; Regeneron Pharmaceuticals, Amryt, Third Rock Ventures. Grant Recipient; Self; Regeneron Pharmaceuticals, Amryt. Research Investigator; Self; Novo Nordisk, Ionis Pharmaceuticals Inc., Fractyl, GI Dynamics, Rhythm Pharmaceuticals. Other; Self; Amryt. Background: Lipodystrophy syndromes (LD) are rare disorders characterized by varying degrees of adipose tissue deficiency that can predispose individuals to severe metabolic complications. Although these syndromes are traditionally subclassified based on inheritance patterns and the degree of adipose tissue loss, patients may exhibit highly heterogeneous clinical presentations. In this context, we report a unique case of partial lipodystrophy with an unusual distribution of adipose tissue that likely represents a novel syndrome and challenges conventional phenotypes. Clinical Case: A 60-year-old Puerto Rican female patient with medical history of type 1 diabetes mellitus (DM), obesity, hyperlipidemia, irritable bowel syndrome, asthma, and coronary artery disease was referred to us for unexplained asymmetric distribution of adipose tissue. She had chronic left posterolateral hip pain and lipoatrophy in her left lower extremity. Her medical history showed that she was born approximately 7 lbs., with no evidence of trauma during delivery. Her mother was given an unknown medication for improving circulation to the placenta. She had a morphea like rash on the arms and chest wall more prominent on the left upper body at birth. In addition, a dimple on her hip was noticed by her mother during the early stages of infancy. Despite the normal progression of neurological development (walking/climbing stairs), she always had a very mild limp. Also, her right arm was always 2 inches larger than her left arm. When she gained weight, she also put on more asymmetric weight on the left side of the abdomen and left lower torso. She had been treated with insulin injections since she was diagnosed with diabetes at the age of 11. She never demonstrated any islet cell specific antibodies. She had a normal weight until pregnancy at the age of 27, during which she gained 20 lbs. Her weight continued to increase over time, and the maximum was 212 lbs. Her examination reveals a BMI of 41.46 kg/m² with excess fat in the right arm, mid-section, left thigh, and left mons pubis. Conversely, only the left leg appears to demonstrate specific fat atrophy, with a near-total loss of adipose tissue starting from the mid-gluteal region. The hip MRI result reported moderate osteoarthritis of the left hip. EMG revealed signs of length-dependent sensorimotor axonal polyneuropathy and long duration/large amplitude motor unit potentials isolated only in the left medial gastrocnemius muscle. Triglyceride level was 73 mg/dL, HbA1c level was 6.8%, with an average total insulin dosage of around 43 IU/day. There was no history of pancreatitis due to hypertriglyceridemia. Conclusion: Our case highlights the heterogeneity of the lipodystrophy spectrum with a novel presentation of lipodystrophy. In addition, there may be homeostatic control of deposition of fat to seek symmetry between upper versus lower and right versus left sided depots. Presentation: 6/1/2024

9208 Sex Hormones and Abdominal Muscle Area and Radiodensity in Men: A Multi-Ethnic Study of Atherosclerosis

Abstract Disclosure: A. Osmancevic: None. M. Allison: None. I. Miljkovic: None. C. Vella: None. P. Ouyang: None. P. Trimpou: None. B. Daka: None. Context: Information on the associations of testosterone, estradiol and sex hormone binding globulin (SHBG) levels with abdominal muscle volume and quality in men are unclear. Objective: To investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Design: Cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis. Participants: A community-based sample of 907 men aged 45-84 years; 878 men with complete data were included in the analysis. Main Outcome Measure(s): CT scans of the abdomen were interrogated for muscle characteristics. Multivariable linear regressions were used to test the associations. Results: After adjustment for age, race/ethnicity, visceral fat, CRP, lifestyle factors, comorbidities and medicine use, higher levels of both total testosterone and estradiol, but not SHBG, were associated with higher abdominal muscle area (B= 1.79, 95% CI 0.1 to 3.4, &amp; B=1.79, 95% CI 0.4 to 3.2, respectively). After the same adjustment, levels of total testosterone showed a significant positive association (B= 0.3, 95% CI 0.0 to 0.6), while a significant inverse relationship was observed for SHBG with abdominal muscle radiodensity (B=-0.34, 95% CI -0.6 to -0.1). Conclusion: Our results indicate significant associations between sex hormones and abdominal muscle characteristics in men from several different race/ethnic groups. These findings reveal novel insights into the previously unrecognized role that SHBG may play in skeletal muscle adipose tissue distribution. Presentation: 6/2/2024

6448 Metabolic Profile and Adipose Tissue Distribution of Young Individuals with Turner Syndrome

Abstract Disclosure: V.M. Thomas: None. P.F. Backeljauw: Consulting Fee; Self; Novo Nordisk, Ascendis, Biomarin, Cavalry Biosciences, Upsher-Smith Laboratories, Tolmar. Speaker; Self; BioMarin, Ascendis.. A. Shah: None. I. Gutmark-Little: Research Investigator; Self; Novo Nordisk, Ascendis, OPKO. Introduction: Turner syndrome (TS) is the most common sex chromosome abnormality in females. Incidence of type 2 diabetes mellitus, hypertension, and dyslipidemia is high in TS. Current practice is to employ BMI as a proxy for adiposity. However, BMI is not an optimal tool due to the short stature observed in TS. Alternate methods such as the dual-energy x-ray absorptiometry (DXA) scan and bioelectrical impedance (BI) may provide more information about body composition. Objectives: The objective of this study is to assess alternative outpatient methods for body composition assessment, including adiposity in pediatric patients with TS. The secondary goal is to characterize the metabolic profile of pediatric subjects with TS compared to obese (BMI ≥95 th%ile) and lean controls (BMI: 5-85th%ile). Methods: This is a cross-sectional study. TS patients are on ≥50mcg transdermal estradiol equivalent replacement OR are self-menstruating. BI, DXA, metabolic markers, interleukin-6 (IL-6) &amp; C-reactive protein (CRP) were obtained in all 3 groups. Statistical analysis was conducted using SPSS software. Results: We present preliminary data on 15 TS, 12 obese, and 15 lean youth, aged 13-19 years. TS youth averages: Age 16.5±1.3 years; BMI 29.3±8.5 kg/m2 (z-score: 1.21±1.27). DXA visceral adiposity (DXA VA): 392±257 g; BI visceral fat (BI VF): 1300±750 cm². Elevated LDL-C&amp;gt;100 mg/dL was noted in n=5 (102-166). Elevated AST &amp;/or ALT &amp;gt;40 unit/L were found in 6 TS. 6 TS had elevated BI VF and DXA VA (&amp;gt;250g) with BMI z-score &amp;lt;2.0. Increased CRP &amp;/or IL-6 levels were noted in 4 TS (BMI z-score: 1.29-2.54), all of whom had primary ovarian failure. These 4 also had increased DXA VA (358-887 g), and BI VF (1500-2500 cm²) compared to the rest of the group. Obese youth averages: Age 16.7±1.83 years; BMI 38 kg/m2 (z-score: 2.26±0.3); DXA VA 674±226 g; BI VF 2300±390 cm². LDL-C&amp;gt;100 mg/dL noted in n=5 (102-121). AST&amp;ALT&amp;lt;35 units/L for all. Increased CRP &amp;/or IL-6 were noted in 4 study subjects (DXA VA: 474-718 g). All 4 had normal A1c, lipid, and liver profiles. Lean youth averages: Age 16.4±2.4 years, BMI 21.6 kg/m2 (z-score: 0.32±0.7); DXA VA 162±68 g; BI VF: 580±370 cm². LDL-C &amp;gt;100 mg/dL noted in n=3 (106-120); 1 subject had increased AST&amp;ALT &amp;gt;40 unit/L. All others had AST &amp; ALT&amp;lt;26 units/L. Elevated CRP/IL-6 was noted in 4 subjects, 1 of whom had increased DXA VA (367g). All subjects had normal HgA1c (≤5.6). Total mass, lean mass, and fat % from DXA and BI were compared (correlation analysis) for each subject and showed agreement throughout. Conclusion: Based on these preliminary data, BI may be a convenient and noninvasive tool to assess adiposity in the outpatient setting in TS. BI and DXA both detected increased visceral fat in TS subjects with normal BMI. BI could potentially identify TS individuals at risk for metabolic dysfunction. Further studies on larger patient numbers will be needed to confirm these preliminary findings. Presentation: 6/2/2024

7896 Sex Hormones and Abdominal Muscle Area and Radiodensity in Men: A Multi-Ethnic Study of Atherosclerosis

Abstract Disclosure: A. Osmancevic: None. M. Allison: None. I. Miljkovic: None. C. Vella: None. P. Ouyang: None. P. Trimpou: None. B. Daka: None. Context: Information on the associations of testosterone, estradiol and sex hormone binding globulin (SHBG) levels with abdominal muscle volume and quality in men are unclear. Objective: To investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Design: Cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis. Participants: A community-based sample of 907 men aged 45-84 years; 878 men with complete data were included in the analysis. Main Outcome Measure(s): CT scans of the abdomen were interrogated for muscle characteristics. Multivariable linear regressions were used to test the associations. Results: After adjustment for age, race/ethnicity, visceral fat, CRP, lifestyle factors, comorbidities and medicine use, higher levels of both total testosterone and estradiol, but not SHBG, were associated with higher abdominal muscle area (B= 1.79, 95% CI 0.1 to 3.4, &amp; B=1.79, 95% CI 0.4 to 3.2, respectively). After the same adjustment, levels of total testosterone showed a significant positive association (B= 0.3, 95% CI 0.0 to 0.6), while a significant inverse relationship was observed for SHBG with abdominal muscle radiodensity (B=-0.34, 95% CI -0.6 to -0.1). Conclusion: Our results indicate significant associations between sex hormones and abdominal muscle characteristics in men from several different race/ethnic groups. These findings reveal novel insights into the previously unrecognized role that SHBG may play in skeletal muscle adipose tissue distribution. Presentation: 6/2/2024

9208 Sex Hormones and Abdominal Muscle Area and Radiodensity in Men: A Multi-Ethnic Study of Atherosclerosis

Abstract Disclosure: A. Osmancevic: None. M. Allison: None. I. Miljkovic: None. C. Vella: None. P. Ouyang: None. P. Trimpou: None. B. Daka: None. Context: Information on the associations of testosterone, estradiol and sex hormone binding globulin (SHBG) levels with abdominal muscle volume and quality in men are unclear. Objective: To investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Design: Cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis. Participants: A community-based sample of 907 men aged 45-84 years; 878 men with complete data were included in the analysis. Main Outcome Measure(s): CT scans of the abdomen were interrogated for muscle characteristics. Multivariable linear regressions were used to test the associations. Results: After adjustment for age, race/ethnicity, visceral fat, CRP, lifestyle factors, comorbidities and medicine use, higher levels of both total testosterone and estradiol, but not SHBG, were associated with higher abdominal muscle area (B= 1.79, 95% CI 0.1 to 3.4, &amp; B=1.79, 95% CI 0.4 to 3.2, respectively). After the same adjustment, levels of total testosterone showed a significant positive association (B= 0.3, 95% CI 0.0 to 0.6), while a significant inverse relationship was observed for SHBG with abdominal muscle radiodensity (B=-0.34, 95% CI -0.6 to -0.1). Conclusion: Our results indicate significant associations between sex hormones and abdominal muscle characteristics in men from several different race/ethnic groups. These findings reveal novel insights into the previously unrecognized role that SHBG may play in skeletal muscle adipose tissue distribution. Presentation: 6/2/2024

Cardio-Metabolic Index as a Novel Predictor for Metabolic Associated Fatty Liver Disease (MAFLD) In Egyptian Patients

Abstract Background Metabolic associated fatty liver disease (MAFLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is a new definition of liver disease associated with known metabolic dysfunction and is the most common chronic liver disease worldwide. Aim of the Work to investigate the association between the cardiometabolic index (CMI) with risk of metabolism-associated fatty liver disease (MAFLD). Patients and Methods a cross-sectional study. It included 50 patients. It was conducted in Ain Shams University Internal Medicine department for six months from June 2023 to December 2023. Results the study revealed that a wide age group ranging from 22 to 70 years, (mean age of 49.86±12.91 years). There was male to female ratio 1:1, mean of BMI [wt/ (ht)∧2] was 34.17±5.28, WHtR was 0.59±0.09, DM was 22 (44.0%) and HTN was 22 (44.0%). Association between CMI and different parameters was done and resulted in no statistically significant association between CMI and sex, obesity. While it showed statistically significant association between CMI and age groups, higher score of steatosis, higher score of fibrosis, and enlarged liver size. Correlation between CMI with different parameters in patients, using Pearson's correlation coefficient (r) was done and resulted in; statistically significant positive correlation between CMI with age (years), HTN, TG, steatosis score, fibrosis score and size liver, with p-value (p &amp;lt; 0.05). While, there was a statistically significant negative correlation between Cardio-metabolic Index with WHtR and HDL, with p-value (p &amp;lt; 0.05). As for the rest have insignificant correlation, with p-value (p &amp;gt; 0.05). ROC curve analysis proved good discriminating power of the (Cardio-metabolic Index) between positive liver and negative liver for Fibrosis where Area under the ROC curve (AUC) = 0.86 with SE 0.163 (95% Confidence interval 0.72 – 0.94. Z statistic= 6.332, p &amp;lt; 0.001. Cutoff point &amp;gt;5.5 with sensitivity= 87.2% and specificity=81.8. Conclusion The cardiometabolic index (CMI), a recently developed index reflecting visceral adipose tissue (VAT) distribution and dysfunction consisting of anthropometric and biochemical indicators, including waist-to-height ratio (WHtR) and triglyceride to high- density lipoprotein cholesterol ratio (TG/HDL-C), which can be easily obtained during a health examination.

European Association for the Study of Obesity (EASO): a new framework for the diagnosis, staging and management of obesity in adults

Obesity is defined as chronic disease process. However, current guidelines for obesity are not aligned sufficiently with those adopted for other chronic diseases. The diagnosis of obesity is based solely on BMI values, not reflecting the role of adipose tissue distribution and function in the severity of the disease. Indications for using the different therapeutic approaches now available for obesity management remain mostly based on anthropometric measurements, rather than on a complete clinical evaluation. This contrast with other chronic diseases, for which therapeutic targets are set, and the choice of the treatment is based on the probability of reaching the target, with adequate and prompt treatment intensification if needed. To stimulate the development of clinical guidelines for obesity more aligned with those already in place for other chronic diseases, the European Association for the Study of Obesity (EASO) conducted a consensus process to propose a new framework for the diagnosis, staging and management of obesity in adults.

Adipose Tissue Plasticity: A Comprehensive Definition and Multidimensional Insight.

Adipose tissue is composed of adipocytes, stromal vascular fraction, nerves, surrounding immune cells, and the extracellular matrix. Under various physiological or pathological conditions, adipose tissue shifts cellular composition, lipid storage, and organelle dynamics to respond to the stress; this remodeling is called "adipose tissue plasticity". Adipose tissue plasticity includes changes in the size, species, number, lipid storage capacity, and differentiation function of adipocytes, as well as alterations in the distribution and cellular composition of adipose tissue. This plasticity has a major role in growth, obesity, organismal protection, and internal environmental homeostasis. Moreover, certain thresholds exist for this plasticity with significant individualized differences. Here, we comprehensively elaborate on the specific connotation of adipose tissue plasticity and the relationship between this plasticity and the development of many diseases. Meanwhile, we summarize possible strategies for treating obesity in response to adipose tissue plasticity, intending to provide new insights into the dynamic changes in adipose tissue and contribute new ideas to relevant clinical problems.

Impact of Maternal Body Composition, Hydration, and Metabolic Health on Breastfeeding Success: A Comprehensive Review.

It is well established that breastfeeding provides significant health benefits for both the mother and the infant. The World Health Organization recommends initiating breastfeeding within the first hour after birth and continuing exclusive breastfeeding for 6 months. Successful breastfeeding is influenced not only by the proper physiological preparation of the body and the action of pregnancy-related hormones but also by the mother's overall health status. However, the role of maternal body composition and metabolic condition in breastfeeding success has received little attention. To better understand the impact of these factors on breastfeeding effectiveness, we reviewed the latest research on this topic, with particular emphasis on the role of hydration and lipid metabolism. Our narrative review indicates that the amount and distribution of water and adipose tissue are crucial for successful lactation and that various hormonal imbalances and metabolic disorders increase the risk of delayed breastfeeding initiation, shortened breastfeeding duration, or insufficient milk production. In light of our findings, measurement methods for assessing described parameters were also introduced. This article aims to review the effects of maternal body composition, hydration status, and metabolic and social factors on lactation and breastfeeding.

Fundamental Body Composition Principles Provide Context for Fat-Free and Skeletal Muscle Loss With GLP-1 RA Treatments.

During weight loss, reductions in body mass are commonly described using molecular body components (eg, fat mass and fat-free mass [FFM]) or tissues and organs (eg, adipose tissue and skeletal muscle). While often conflated, distinctions between body components established by different levels of the 5-level model of body composition-which partitions body mass according to the atomic, molecular, cellular, tissue/organ, or whole-body level-are essential to recall when interpreting the composition of weight loss. A contemporary area of clinical and research interest that demonstrates the importance of these concepts is the discussion surrounding body composition changes with glucagon-like peptide-1 receptor agonists (GLP-1RA), particularly in regard to changes in FFM and skeletal muscle mass. The present article emphasizes the importance of fundamental principles when interpreting body composition changes experienced during weight loss, with a particular focus on GLP-1RA drug trials. The potential for obligatory loss of FFM due to reductions in adipose tissue mass and distribution of FFM loss from distinct body tissues are also discussed. Finally, selected countermeasures to combat loss of FFM and skeletal muscle, namely resistance exercise training and increased protein intake, are presented. Collectively, these considerations may allow for enhanced clarity when conceptualizing, discussing, and seeking to influence body composition changes experienced during weight loss.