Truncal Fat Research Articles

Fat Distribution and Urolithiasis Risk Parameters in Uric Acid Stone Formers and Patients with Type 2 Diabetes Mellitus.

Key Points Under a controlled diet, uric acid stone formers (UASFs) and diabetic patients have higher endogenous net acid production.Under a controlled diet, UASFs have lower ammonium-to-net acid excretion ratio.Body fat inversely correlates with urine buffer capacity in normal individuals, but this relationship is lost in diabetic patients and UASFs. Background Uric acid (UA) nephrolithiasis affects approximately 10% of kidney stones, with a greater preponderance among patients with obesity and diabetes mellitus (DM). UA lithogenicity is driven by abnormally acidic urine pH. Distinguishing the contribution of intrinsic (e.g., body adiposity) versus external (e.g., dietary) factors to UA stone propensity is challenging because of uncontrolled diets in outpatients in previously published studies. Methods This compilation of metabolic studies with body composition examined by dual-energy x-ray absorptiometry scan and blood and urine biochemistry collected under a controlled metabolic diet was conducted across three distinct populations: 74 UA stone formers (UASF group), 13 patients with type 2 DM without kidney stones (DM group), and 51 healthy volunteers (HV group). Results Compared with HVs, both UASFs and patients with DM exhibited higher levels of net acid excretion (NAE) and significantly lower urine pH and lower proportion of NAE excreted as ammonium (NH4 +/NAE), all under controlled diets. UASFs exhibited significantly lower NH4 +/NAE compared with patients with DM. UASFs also showed higher total body and truncal fat compared with HVs. Among the HVs, lower NH4 +/NAE ratio correlated with higher truncal and total fat. However, this association was abolished in the UASF and DM groups who exhibit a fixed low NH4 +/NAE ratio across a range of body and truncal fat. Conclusions The findings suggest a dual defect of diet-independent increase in acid production and impaired kidney NH4 + excretion as major contributors to the risk of UA stone formation. There is an inverse physiologic association between body fat content and NH4 +/NAE in HVs, whereas NH4 +/NAE is persistently low in UASFs and patients with DM, regardless of body fat, representing pathophysiology.

7515 Plasma proteomic signatures for type 2 diabetes mellitus and related traits in the UK Biobank

Abstract Disclosure: T. Gupte: None. Z. Azizi: None. K. Nzenkue: None. P. Kho: None. M. Chen: None. J. Zhou: None. R. Guarischi-Sousa: None. D.J. Panyard: None. F. Abbasi: None. K. Watson: None. S. Clarke: None. P.S. Tsao: None. T.L. Assimes: None. Background: The plasma proteome holds promise as a future diagnostic and prognostic tool that can accurately reflect complex human traits and disease processes. We assessed the ability of plasma proteins to associate with two primary risk factors of type 2 diabetes mellitus (T2DM) and to predict incident T2DM. Methods: Clinical, genetic, and high-throughput proteomic data from three subcohorts of 5586, 5584, and 36339 individuals in the UK Biobank were analyzed for association with DXA-measured truncal fat, maximum VO2, and incident T2DM, respectively. Exclusion criteria included prevalent T2DM, history of T1DM, or elevated A1c (>48 mmol/mol) values. We used LASSO to assess relative ability of 13 clinical variables including the Q-Diabetes (Q-D) score, 36 polygenic risk scores (PRSs), and 2923 proteins to associate with each trait by comparing variances explained (R2) and AUC statistics between data types. Stability selection with randomized LASSO identified the most robustly associated proteins for each trait. The benefit of proteomic signatures (PSs) over the Q-D score was evaluated through the derivation of Δ AUC values. Separate case-control groups were developed to evaluate T2DM prediction in the adiposity and fitness cohorts. Results: Across all three subcohorts, the mean age was 56.6 years, 54.9% were female, and 5.4% developed T2DM over a median follow-up of 7.7 years. In the adiposity cohort, a protein-only LASSO model explained 73.2% of the variance in truncal fat and GLIPR1, CLMP, LEP, FABP4, and FAM3C were among the top proteins selected. In the fitness cohort, a protein-only LASSO model explained 61.9% of the variance in maximum VO2 and LEP, CD99, AGRN, ELN, and CA14 were among the top proteins selected. LASSO-derived PSs increased the R2 of truncal fat and maximum VO2 over clinical and genetic factors by 13% and 1%, respectively, with the former also improving risk prediction of T2DM over Q-D [Δ AUC: 0.026 (95% CI -0.007, 0.060)]. In the T2DM cohort, a protein-only LASSO model returned an AUC of 0.856 (95% CI 0.840, 0.871) and PLXNB2, PODXL, PLA2G7, FGFR2, and NFASC were among the top proteins selected. We observed a similar improvement in T2DM prediction over Q-D [Δ AUC: 0.015 (95% CI 0.009, 0.023)] when using a PS derived strictly from the T2DM outcome and augmented with non-overlapping proteins associated with fat and fitness. A few proteins (ranging between 15-33 for each trait) identified by stability selection algorithms offered most of the improvement in risk prediction. Conclusion: Plasma PS modestly improves the prediction of T2DM over that possible with clinical and genetic factors. Further studies are warranted to better elucidate the clinical utility of these signatures in predicting T2DM risk over the standard practice of using the Q-D score. Presentation: 6/2/2024

Plasma proteomic signatures for type 2 diabetes mellitus and related traits in the UK Biobank cohort.

The plasma proteome holds promise as a diagnostic and prognostic tool that can accurately reflect complex human traits and disease processes. We assessed the ability of plasma proteins to predict type 2 diabetes mellitus (T2DM) and related traits. Clinical, genetic, and high-throughput proteomic data from three subcohorts of UK Biobank participants were analyzed for association with dual-energy x-ray absorptiometry (DXA) derived truncal fat (in the adiposity subcohort), estimated maximum oxygen consumption (VO2max) (in the fitness subcohort), and incident T2DM (in the T2DM subcohort). We used least absolute shrinkage and selection operator (LASSO) regression to assess the relative ability of non-proteomic and proteomic variables to associate with each trait by comparing variance explained (R2) and area under the curve (AUC) statistics between data types. Stability selection with randomized LASSO regression identified the most robustly associated proteins for each trait. The benefit of proteomic signatures (PSs) over QDiabetes, a T2DM clinical risk score, was evaluated through the derivation of delta (Δ) AUC values. We also assessed the incremental gain in model performance metrics using proteomic datasets with varying numbers of proteins. A series of two-sample Mendelian randomization (MR) analyses were conducted to identify potentially causal proteins for adiposity, fitness, and T2DM. Across all three subcohorts, the mean age was 56.7 years and 54.9% were female. In the T2DM subcohort, 5.8% developed incident T2DM over a median follow-up of 7.6 years. LASSO-derived PSs increased the R2 of truncal fat and VO2max over clinical and genetic factors by 0.074 and 0.057, respectively. We observed a similar improvement in T2DM prediction over the QDiabetes score [Δ AUC: 0.016 (95% CI 0.008, 0.024)] when using a robust PS derived strictly from the T2DM outcome versus a model further augmented with non-overlapping proteins associated with adiposity and fitness. A small number of proteins (29 for truncal adiposity, 18 for VO2max, and 26 for T2DM) identified by stability selection algorithms offered most of the improvement in prediction of each outcome. Filtered and clustered versions of the full proteomic dataset supplied by the UK Biobank (ranging between 600-1,500 proteins) performed comparably to the full dataset for T2DM prediction. Using MR, we identified 4 proteins as potentially causal for adiposity, 1 as potentially causal for fitness, and 4 as potentially causal for T2DM. Plasma PSs modestly improve the prediction of incident T2DM over that possible with clinical and genetic factors. Further studies are warranted to better elucidate the clinical utility of these signatures in predicting the risk of T2DM over the standard practice of using the QDiabetes score. Candidate causally associated proteins identified through MR deserve further study as potential novel therapeutic targets for T2DM.

A PRDM16-driven signal regulates body composition in testosterone-treated hypogonadal men.

Testosterone (T) therapy increases lean mass and reduces total body and truncal fat mass in hypogonadal men. However, the underlying molecular mechanisms for the reciprocal changes in fat and lean mass in humans are not entirely clear. Secondary analysis of specimens obtained from a single-arm, open-label clinical trial on pharmacogenetics of response to T therapy in men with late-onset hypogonadism, conducted between 2011 and 2016 involving 105 men (40-74 years old), who were given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subcutaneous fat (SCF), peripheral blood mononuclear cells (PBMC) and serum were obtained from the participants at different time points of the study. We measured transcription factors for adipogenesis and myogenesis in the SCF, and PBMC, respectively, by real-time quantitative PCR at baseline and 6 months. Serum levels of FOLLISTATIN, PAX7, MYOSTATIN, ADIPSIN, and PRDM16 were measured by ELISA. As expected, there was a significant increase in T and estradiol levels after 6 months of T therapy. There was also a reduction in fat mass and an increase in lean mass after 6 months of T therapy. Gene-protein studies showed a significant reduction in the expression of the adipogenic markers PPARγ in SCF and ADIPSIN levels in the serum, together with a concomitant significant increase in the expression of myogenic markers, MYOD in PBMC and PAX7 and FOLLISTATIN levels in the serum after 6 months of T therapy compared to baseline. Interestingly, there was a significant increase in the adipo-myogenic switch, PRDM16, expression in SCF and PBMC, and in circulating protein levels in the serum after 6 months of T therapy, which is likely from increased estradiol. Our study supports that molecular shift from the adipogenic to the myogenic pathway in men with hypogonadism treated with T could be mediated directly or indirectly by enhanced PRDM16 activity, in turn a result from increased estradiol level. This might have led to the reduction in body fat and increase in lean mass commonly seen in hypogonadal men treated with T.

Association between bone age maturity and childhood adiposity.

Evidence shows that overweight and obesity are associated with advanced bone age (BA). To analyse the effect of adiposity on BA among Mexican children. This cross-sectional study included 902 children (5-18 years old). Anthropometric measurements, dual-energy X-ray absorptiometry (DXA) and automated hand X-ray-based BA measurements were obtained. BA curves of children stratified by sex and age were created based on nutritional status. We also calculated odds ratios for advanced BA associated with the body mass index (BMI), waist/height ratio and adiposity estimated using DXA (total and truncal fat mass). Participants with overweight/obesity by BMI (SDS ≥1) advanced earlier in BA than did normal weight participants (6.0 vs. 12.0 years in boys and 6.0 vs. 10.3 in girls, p < 0.01); similarly, participants with a greater body fat percentage (SDS ≥1) exhibited earlier advanced BA (7.5 vs. 10.0 years in boys and 6.0 vs. 9.6 in girls, p < 0.01). Differences were also observed according to the waist/height ratio and truncal fat. Children with a BMI or DXA SDS ≥1 had greater odds of presenting an advanced BA of more than 1 year (OR 1.79-3.55, p < 0.05). Increased adiposity in children, mainly in boys, is associated with advanced BA at earlier ages.

Plasma metabolomic profile of adiposity and body composition in childhood: The Genetics of Glucose regulation in Gestation and Growth cohort.

This study identified metabolite modules associated with adiposity and body fat distribution in childhood using gold-standard measurements. We used cross-sectional data from 329 children at mid-childhood (age 5.3 ± 0.3 years; BMI 15.7 ± 1.5 kg/m2) from the Genetics of Glucose regulation in Gestation and Growth (Gen3G), a prospective pre-birth cohort. We quantified 1038 plasma metabolites and measured body composition using the gold-standard dual-energy x-ray absorptiometry (DXA), in addition to skinfold, waist circumference, and BMI. We applied weighted-correlation network analysis to identify a network of highly correlated metabolite modules. Spearman's partial correlations were applied to determine the associations of adiposity with metabolite modules and individual metabolites with false discovery rate (FDR) correction. We identified a 'green' module of 120 metabolites, primarily comprised of lipids (mostly sphingomyelins and phosphatidylcholine), that showed positive correlations (all FDR p < 0.05) with DXA estimates of total and truncal fat (ρadjusted = 0.11-0.19), skinfold measures (ρadjusted = 0.09-0.26), and BMI and waist circumference (ρadjusted = 0.15 and 0.18, respectively). These correlations were similar when stratified by sex. Within this module, sphingomyelin (d18:2/14:0, d18:1/14:1)*, a sphingomyelin sub-specie that is an important component of cell membranes, showed the strongest associations. A module of metabolites was associated with adiposity measures in childhood.

High-quality research on physical therapy in psoriatic arthritis is needed: a systematic review.

Although physical therapy is recommended as part of the non-pharmacological management of patients with psoriatic arthritis (PsA), the evidence is still unclear. Therefore, this study aimed to systematically review and appraise the quality of research on physical therapy in the management of patients with PsA. In June 2024, a systematic literature search using four different databases (Medline, Embase, Web of Science and the Cochrane Library) was performed to include interventional and observational studies examining physical therapy in patients with PsA (PROSPERO ID 255501). A risk of bias assessment was conducted. Due to the wide variety of interventions and outcomes, a narrative synthesis was used. Of 9442 abstracts, 15 papers examining physical therapy uptake in clinical practice (N = 2) and different physical therapy interventions (N = 13) were included: cardiorespiratory exercises (N = 5), resistance exercises (N = 2), therapeutic modalities (N = 4) and mixed rehabilitation programs (N = 2). A low risk of bias was scored in only one RCT assessing cardiorespiratory exercises. The well-tolerated 11-week high-intensity interval training resulted in a long-term increase in peak oxygen uptake and a short-term decrease in truncal fat percentage in patients with low disease activity. Resistance training in patients with active disease did not increase muscle strength, but improved functional capacity, disease activity, pain and general health after the intervention. Evidence for other modalities was inconclusive. High-quality evidence on physical therapy in PsA was scarce. Cardiorespiratory and resistance exercises demonstrated promising results to positively influence cardiometabolic risk as well as disease-related outcomes. Future research on physical therapy in PsA with adequate methodological quality is needed.

Clinical Implications of Fat Grafting in the Posterior Calf: A Dynamic Cadaver-based Study.

Intramuscular fat grafting in extremity muscles, especially the gastrocnemius, has become increasingly popular. However, while safety in truncal muscle fat grafting has been well-studied, research on extremity muscles is lacking. In this study, we aimed to explore the anatomy of the gastrocnemius muscle and adjacent structures as intramuscular and subcutaneous recipient sites. Additionally, we sought to analyze pressure-volume relationships and fat migration patterns during posterior calf grafting. Eight cadaveric lower extremities were examined. A prosection was performed to better understand the vascular complex around the gastrocnemius. Ultrasound-guided fat injections were then performed into both the subcutaneous and intramuscular layers; dynamic pressures were measured with a manometer. Last, dyed-injectant was injected subcutaneously to better elucidate subcutaneous anatomy. Anatomic prosection demonstrated the proximity of the gastrocnemius muscle to the popliteal venous system that arborized (>1 mm) intramuscularly. In the 3 specimens that underwent intramuscular fat grafting, the peak intramuscular pressures plateaued at 21 mmHg (19.5-23 mmHg); there was no observed extrafascial migration of the injectant. With subcutaneous injectant in 1 specimen, pressures in the subcutaneous space increased (125 mmHg) with additional injectant (240 mL) while pressures in the intramuscular space remained relatively constant (4 mmHg). Intramuscular gastrocnemius fat grafting should be done with caution: its proximity to critical veins and sustained increased intramuscular pressures following grafting increases risks of embolus and thrombosis, respectively. Subcutaneous injection may be safer in that increased pressures are not communicated to deep structures. Last, we present a novel description of posterior calf subcutaneous compartments that may better allow surgeons to direct and predict subcutaneous injectant.

Associations of Childhood Adiposity and Cardiometabolic Biomarkers With Adolescent PCOS.

Polycystic Ovary Syndrome (PCOS) is common among females, with significant metabolic and reproductive comorbidities. We describe PCOS development in a pediatric population. We assessed cardiometabolic biomarkers and adiposity at the midchildhood (mean 7.9 y), early teen (mean 13.1 y), and midteen (mean 17.8 y) visits among 417 females in the prospective Project Viva cohort. We defined PCOS via self-reported diagnosis or ovulatory dysfunction with hyperandrogenism in midlate adolescence. We used multivariable logistic regression to assess associations of metabolic and adiposity markers at each visit with PCOS. Adolescents with PCOS (n = 56, 13%) versus without had higher mean (SD) BMI z-score and truncal fat mass at the midchildhood (0.66 [0.99] vs 0.30 [1.04]; 3.5 kg [2.6] vs 2.7 [1.5]), early teen (0.88 [1.01] vs 0.25 [1.08]; 9.4 kg [6.7] vs 6.1 [3.4]), and midteen (0.78 [1.03] vs 0.33 [0.97]; 11.6 kg [7.2] vs 9.1 [4.9]) visits as well as lower adiponectin to leptin ratio at the early (0.65 [0.69] vs 1.04 [0.97]) and midteen (0.33 [0.26] vs 0.75 [1.21]) visits. In models adjusted for maternal PCOS, education and child race and ethnicity (social factors), we found higher odds of PCOS per 1-SD increase in truncal fat at midchildhood (odds ratio [OR] 1.42; 95% confidence interval [CI] 1.03-1.95) and early teen visits (OR 1.61; 95% CI 1.14-2.28) and lower odds per 1-SD increase in adiponectin/leptin ratio at the midteen visit (OR 0.14; 95% CI 0.03-0.58). Childhood excess adiposity and adipose tissue dysfunction may be a first signs of later PCOS risk.

Association of Aldosterone, Renin, and Aldosterone to Renin Ratio with Metabolic Profile in Primary Aldosteronism.

This study aimed to investigate the glycometabolism, fat mass, and lean mass in primary aldosteronism (PA) during disease progression. Patients diagnosed with PA and healthy controls (HCs) were enrolled. A flash glucose monitoring system (FGMS) and dual-energy X-ray absorptiometry (DEXA) were used to measure glucose variability and glucose target rate along with fat mass and lean mass. Comparative analysis of FGMS- or DEXA-derived parameters along with correlation analyses between these parameters and PA progression were performed. Increased glucose variability and poor glucose target rate, along with an increased proportion of truncal fat mass, and decreased proportion of appendicular lean mass, were identified in PA group compared to those in HCs. Plasma aldosterone concentration was positively correlated with glucose variability and poor glucose target rate. Plasma renin concentration was positively correlated with the proportion of truncal fat mass and lean mass, and negatively correlated with the proportion of appendicular fat mass. Aldosterone-to-renin ratio was negatively correlated with the proportion of truncal fat mass and lean mass, and positively correlated with the proportion of appendicular fat mass. Patients with PA presented significant differences in glycometabolism, fat mass, and lean mass compared with HCs, and these alterations correlated with PA progression.

Comparison of anthropometric, metabolic, and body compositional abnormalities in Korean children and adolescents born small, appropriate, and large for gestational age: a population-based study from KNHANES V (2010-2011).

The impacts of growth restriction and programming in the fetal stage on metabolic and bone health in children and adolescents are poorly understood. Moreover, there is insufficient evidence for the relationship between current growth status and metabolic components. Herein, we compared the growth status, metabolic and body compositions, and bone mineral density in Korean children and adolescents based on birth weight at gestational age. We studied 1,748 subjects (272 small for gestational age [SGA], 1,286 appropriate for gestational age [AGA], and 190 large for gestational age [LGA]; 931 men and 817 women) aged 10-18 years from the Korean National Health and Nutrition Examination Survey (KNHANES) V (2010-2011). Anthropometric measurements, fasting blood biochemistry, and body composition data were analyzed according to birth weight and gestational age. The prevalence of low birth weight (14.7% vs. 1.2% in AGA and 3.2% in LGA, p<0.001) and current short stature (2.237 [1.296-3.861] compared to AGA, p=0.004) in SGA subjects was greater than that in other groups; however, the prevalence of overweight and obesity risks, metabolic syndrome (MetS), and MetS component abnormalities was not. Moreover, no significant differences were found in age- and sex-adjusted lean mass ratio, fat mass ratio, truncal fat ratio, bone mineral content, or bone density among the SGA, AGA, and LGA groups in Korean children and adolescents. Our data demonstrate that birth weight alone may not be a determining factor for body composition and bone mass in Korean children and adolescents. Further prospective and longitudinal studies in adults are necessary to confirm the impact of SGA on metabolic components and bone health.

Which sub-compartments of fat mass and fat-free mass are related to blood viscosity factors?

The size of body compartments is a determinant of several factors of blood viscosity. Red cell aggregation is proportional to fat mass while hematocrit is proportional to both fat-free mass and abdominal adiposity, but which parts of these body components are involved in this relationship is not known. Segmental bioelectrical impedance analysis (sBIA) provides a possibility to delineate the relationships more precisely between various subdivisions of the body and blood viscosity factors, going farther than preceding studies using non segmental BIA. In this study we investigated in 38 subjects undergoing a standardized breakfast test with mathematical modelling of glucose homeostasis and a segmental bioelectrical impedance analysis (sBIA) the relationships between the various compartments of the body and viscosity factors. Blood and plasma viscosity were measured with the Anton Paar rheometer and analyzed with Quemada's model. The parameters better correlated to hematocrit are fat free mass (r = 0.562) and its two components muscle mass (r = 0.516) and non-muscular fat-free mass (r = 0.452), and also trunk fat mass (r = 0.383) and waist-to hip ratio (r = 0.394). Red cell aggregation measurements were correlated with both truncal and appendicular fat mass (r ranging between 0.603 and 0.728). Weaker correlations of M and M1 are found with waist circumference and hip circumference. This study shows that the correlation between lean mass and hematocrit involves both muscle and non-muscle moieties of lean mass, and that both central and appendicular fat are determinants of red cell aggregation.

Randomized Trial to Improve Body Composition and Micronutrient Status Among South African Children

IntroductionPhysical activity (PA) promotion combined with multi-micronutrient supplementation (MMNS) among school-age children may reduce fat mass accrual and increase muscle mass through different mechanisms and so benefit child health. This study determined the efficacy of combined interventions on body composition among South African schoolchildren and determined if micronutrients mediate these effects. Study designLongitudinal cluster randomized controlled trial of children followed from 2019 to 2021. Statistical analyses carried form 2022-2023 Setting/participantsA total of 1304 children 6-12 years of age recruited from public schools in Gqeberha, South Africa. InterventionChildren were randomized by classes to either: (a) a physical activity group (PA); (b) a MMNS group; (c) a physical activity + multi-micronutrient supplementation group (PA + MMNS); and (d) a placebo control group. Main outcome measuresTrajectories of overall and truncal fat free mass (FFM) and fat mass (FM) estimates in modeled at 9 and 21 months using latent growth curve models (LGCM). Changes in micronutrient concentrations at 9 months from baseline. ResultsAn increased FFM trajectory was found among children in the MMNS arm at 9 months (Beta 0.16, 95% CI = 0.12, 0.31). The PA and MMNS arms both had positive indirect effects on this trajectory at 9 months (Beta 0.66, 95% CI = 0.44, 0.88 and Beta 0.32 95% CI = 0.1 0.5, respectively) and similarly at 21 months when mediated by zinc concentration changes. A reduced FM trajectory was found among children in the PA promotion arm at 9 months when using this collection point as the referent intercept. This arm was inversely associated with the FM trajectory at 9 months when mediated by zinc changes. ConclusionsPA and MMNS promotion in school-based interventions directly contributed to reductions in FM and increased FFM among South African children and indirectly through changes in micronutrient status.

Age-related variations in trunk composition and patterns of regional bone and soft tissue changes in adult Caucasian women by DXA.

We explored the regional variations in body composition with advancing age in healthy Caucasian females living in the Mediterranean area. The objectives of this study were to establish body composition values for the trunk in healthy women of a Greek origin and to evaluate the effects of aging on the distribution of truncal bone mass, fat mass (FM) and lean mass (LM). Body composition of the trunk and detailed analysis of its anatomical components-the ribs, the thoracic spine, the lumbar spine and the pelvis, and FM and LM ratios--were calculated in 330 women aged 20-85years, using DXA. Peak bone mineral density (BMD) of the trunk was attained between ages 30 and 33. The overall truncal BMD reduction with age was 20.7% (p < 0.001). Peak %LM of the trunk was achieved at age 20. The overall reduction of %LM with age for the trunk was 9.8% (p < 0.001). Peak %FM of the trunk was attained between ages 68 and 73, and the overall %FM reduction with age was 2.8% (p > 0.05). Multiple comparative analyses showed that the 51-60years age group was the landmark age for significant changes of truncal bone mass measures across all age groups (p = 0). For truncal LM and FM metrics, multigroup comparative analysis showed the turning point of significant changes in soft tissue was the 41-50 age bracket (p = 0 and p = 0, respectively). In Greek women, truncal %LM exceeded by far %FM across all ages (p = 0). Our results suggest that aging affects body composition of the trunk in ambulatory healthy women of a Greek origin differently, leading to menopausal loss of bone mass, senior adulthood loss of lean mass, and middle-age storage of fat mass. In adult women, these age-related associations between bone and soft tissue metrics on DXA exams carry implications for the attainment of optimal peak values and shifts in body composition overtime, impacting lifelong skeletal health.

Abnormal Body Composition Increases the Cardiometabolic Risk in Adolescents and Young Adults With Turner Syndrome

ObjectiveTo determine the cardiometabolic risk of adolescents and adults with Turner syndrome (TS) and whether and how anthropometry and body composition predict this risk. MethodsWe compared the anthropometric, biochemical, and dual-energy x-ray absorptiometry–derived body composition parameters of 103 girls and women with TS aged 12 to 30 years and 103 controls of the same age and body mass index: (1) between TS with and without metabolic syndrome (MetS), (2) between the different karyotypes of TS, and (3) between growth hormone recipients and nonrecipients. ResultsIndividuals with TS had higher prevalence rates of truncal obesity (57.2%), MetS (37.9%), prediabetes (20.4%), dyslipidemia (73.8%), hypertension (9.7%), and hepatic steatosis (15.5%) and a greater total body fat percentage (38.43% vs 34.26%) and fat mass index (9.15 vs 6.71 kg/m2) but a lower lean mass index (11.05 vs 12.49 kg/m2) than controls (P <.001). Individuals with TS and MetS (n = 39) had a higher total body fat percentage (41.74% vs 36.42%, P <.0001), truncal fat percentage (44.66% vs 36.09%, P <.0001), and visceral adipose tissue mass (495.57 vs 276 g, P <.0001) than those with TS but without MetS. Those with classic TS (45,X) had a higher prevalence of prediabetes (32.6% vs 10.5%, P =.01). Growth hormone recipients had a lower prevalence of MetS and lesser truncal obesity. Altered body composition was significantly correlated with metabolic risk. The truncal fat percentage independently predicted MetS (odds ratio, 1.12; 95% confidence interval, 1.003-1.24; P =.04). Waist circumference and waist-hip ratio predicted metabolic risk with good sensitivity and specificity. ConclusionAdverse cardiometabolic risk and altered body composition start early in life in TS. Postpubertal women with TS should be routinely assessed for truncal obesity, dysglycemia, dyslipidemia, and liver steatosis, irrespective of body mass index and karyotype.

Poor vitamin D status was associated with increased appendicular fat deposition in US Adults: Data from 2011–2018 National Health and Nutrition Examination Survey

The aim of the study was to explore the relationship between serum 25-hydroxyvitamin D [25(OH)D] concentrations and regional body fat deposition in 2011–2018 National Health and Nutrition Examination Survey participants aged 18 to 59 years. We hypothesized that serum 25(OH)D concentrations were negatively associated with total, appendicular, and truncal fat deposition. Serum 25(OH)D concentration was categorized into sufficient (≥75.0 nM), insufficient (50.0–74.9 nM), and deficient (<50.0 nM) groups. Fat mass (FM) was measured by dual-energy X-ray absorptiometry, and FM index (FMI) was calculated by dividing FM (kg) with height2 (m2). Multivariant linear regression and Granger causal analysis were performed to assess the causal relationship between vitamin D status and regional FMIs. Overall serum 25(OH)D concentrations were negatively associated with total (β = –0.029, standard error [SE] = 0.002), trunk (β = –0.015, SE = 0.001), arms (β = –0.004, SE = 3.09 × 10−4), and legs (β = –0.010, SE = 0.001) FMIs in all participants (P < .001, respectively); however, after stratified by vitamin D status and BMI, the negative associations were only observed in individuals with vitamin D deficiency and obesity. The causal analysis indicated that serum 25(OH)D concentrations may causally reduce the arms (F = 4.917, probability [P] = 0.007), legs (F = 5.783, P = 0.003), and total (F = 3.202, P = 0.041) FMIs except for trunk FMI but not vice versa. In conclusion, poor vitamin D status was associated with increased total and appendicular body fat deposition in US adults, particularly in participants with obesity.

Alterations of cardiometabolic risk profile in polycystic ovary syndrome: 13years follow-up in an unselected population.

Cardiometabolic risk factors are common in women with polycystic ovary syndrome (PCOS) during reproductive years. The aim of this study wasto determine the impact of aging on cardiometabolic risk of the syndrome by examining womenwho had previously been diagnosedto have PCOS or to be healthy in an unselected population in 2009. Forty-one women with PCOS who were diagnosed and phenotyped according to the Rotterdam criteria and 43 age- and body mass index (BMI)-matched healthy women from the same unselected cohort. All participants were evaluated by structured interview, physical examination, anthropometric, hormonal and biochemical measurements. Additionally, body composition analyses and echocardiographic assessments of 30 women with PCOS and 30 control women were conducted at 13 years of follow-up. There was no difference between the patient and the control groups in terms of anthropometric and body composition measures and metabolic parameters. Echocardiographic assessment showed similar systolic functions, strain measurements and epicardial fat measurements between the groups. PCOS patients still had higher levels of total testosterone, free androgen index (FAI) and dehydroepiandrosterone sulfate (DHEAS) levels compared to controls. Epicardial fat thickness showed positive correlations with BMI, total and truncal body fat, homeostatic model assessment for insulin resistance (HOMA-IR) and free androgen index (FAI). Aging women with PCOS in the population have higher androgen levels and similar cardiometabolic risk profile compared to age- and BMI-matched healthy women. Epicardial fat thickness, a marker of cardiometabolic risk, appear to be associated with hyperandrogenism. Further research is needed on larger community-based cohorts where older patients are assessed with a longer follow-up.

THU115 Sex-Specific And Shared Associations Between Vasopressin Levels And Body Composition In Adults With Obesity

Abstract Disclosure: F. Galbiati: None. M. Wronski: None. A. Aulinas Maso: None. M. Muhammed: None. R. Boutin: None. K. Liya: None. S. Carter: None. H. Nazarloo: None. J.M. Davis: None. K. Holman: None. J. Gydus: None. S. Smith: None. E. Asanza: None. M. Bredella: None. M. Torriani: None. F. Plessow: None. E.A. Lawson: Advisory Board Member; Self; OXT Therapeutics. Grant Recipient; Self; Tonix Pharmaceuticals. Background: Arginine-vasopressin (AVP) is a sexually dimorphic neurohormone shown in preclinical studies to have relevant metabolic effects, including reducing food intake, inducing lipolysis, and promoting muscle regeneration in male mice. However, findings are inconsistent, possibly due to the opposing effects of AVP at different receptor subtypes, and little is known about the effects of AVP on metabolism in humans. We hypothesized that AVP may act as signal of energy availability, such that in adults with obesity, integrated AVP levels around a standardized meal would be positively associated with BMI, adiposity, and lean mass. We also predicted that relationships between AVP and body composition measures would differ by sex. Methods: We performed a cross-sectional study of 53 adults with obesity (56% females; age [mean±SD] 33.7±6.2 years; BMI 36.9±4.9 kg/m2). We obtained plasma AVP levels fasting and 30, 60, and 120 minutes after a standardized meal. We computed area under the curve with respect to ground (AUC) for an integrated measure of AVP levels around the meal. Participants underwent body composition assessment by dual-energy X-ray absorptiometry (total fat, truncal fat, and lean mass) and magnetic resonance imaging (abdominal visceral and subcutaneous fat). We performed Pearson’s correlation (normally distributed variables) and Spearman’s correlation (non-normally distributed variables) to investigate the relationship between AVP levels and body composition parameters. Fisher’s Z test was performed to analyze the difference between correlation coefficients across sexes. Results: Age and AVP AUC did not differ based on sex (p=0.300). Total fat mass (p=0.013) was higher while total lean mass (p&amp;lt;0.0001) and abdominal visceral fat (p=0.001) were lower in females than males; BMI, truncal fat, and abdominal subcutaneous fat did not differ by sex (p’s≥0.09). Across all participants, AVP AUC levels were positively correlated with BMI (rs=0.36, p=0.008), total fat mass (r=0.33, p=0.013), truncal fat (r=0.35; p=0.010), abdominal subcutaneous fat (r=0.30, p=0.028), and total lean mass (r=0.38, p=0.005), but not with abdominal visceral fat (p=0.331). Within sex-based group, a robust positive correlation between AVP AUC and abdominal subcutaneous fat mass was present in males (r=0.56, p=0.004), but not females (r=0.04, p=0.592) [(by Fisher’s Z test, p=0.024). There were no other sex differences in correlations (by Fisher’s Z test, p≥0.108). Conclusions: Our data in humans showing a link between integrated AVP and body composition support preclinical data indicating that AVP is a metabolically active hormone. Additionally, we identified sex differences in the relationship between AVP and subcutaneous fat mass. Further investigation of sex-specific and shared metabolic effects of AVP in humans will be important. Presentation: Thursday, June 15, 2023

OR27-01 Upregulated Prdm16 Impairs Adipogenesis And Promotes Myogenesis Via PAX7 And Osteogenesis In Testosterone-treated Hypogonadal Men

Abstract Disclosure: S. Bathina: None. M. Prado: None. L. Aguirre: None. G. Colleluori: None. E. Ballato: None. F. Deepika: None. V. Fuenmayor Lopez: None. D.T. Villareal: None. R.A. Villareal: None. Background: Testosterone (T) therapy increases lean mass; reduces total body and truncal fat mass and increases bone density in hypogonadal men. However, the underlying mechanisms for these changes remain unclear. In this study, we investigated the mechanisms involved for these effects of T on body composition and bone. Objective: Our aims are to evaluate the changes in 1) the gene and protein machinery involved the adipo-myogenic switch, and 2) the cellular osteogenic markers, in-vivo, in response to T therapy. Methods and Study design: Secondary analysis of specimens obtained from a single-arm, open-label clinical trial (NCT01378299) on pharmacogenetics of response to T therapy conducted between 2011-2016 N=105 men (40-74 years old), with average morning T &amp;lt;300 ng/dL who were given intramuscular T cypionate 200 mg every 2 weeks for 18 months As earlier results from our lab, effect of T therapy is maximal after 6 months, we chose to study the specimens at baseline (BL) and 6 months (6M). We measured the adipogenic transcription factors (PPARγ, CEBPa), enzymes (LPL, Adipsin) from subcutaneous fat, and myogenic lineage (Myf5, MyoD), Prdm16 and Pax7 from buffy coat by real-time quantitative PCR at BL and 6M. Serum Follistatin, PRDM16, PAX7 Myostatin, Adipsin were measured by ELISA. Changes in circulating osteogenic precursors (COP) and osteoclast precursors (OCPs) by Flow cytometry, and gene expression of osteoblastic transcription factor, Runx2, by PCR of buffy coat. OCPs in response to testosterone therapy were evaluated from samples of men participating in an ongoing clinical trial (NCT03887936). Results: T therapy decreased PPARg (BL: 2.59±2.2 vs 6M: 1.23±1.0, p=0.03); CEBPa (BL: 3.0±2.57 vs 6M: 1.7±1.2, p=0.10) LPL (BL: 2.81±2.7 vs 6M: 1.74±2.2, p=0.27) in sub-cutaneous fat tissue and increased the expression of MyoD (BL:1.34±1.6 vs 6M: 8.2±12.7, p=0.02) and Myf5 (BL: 6.1±9.7 vs 6M: 12.9±27.7, p=0.26) along with the adipo-myogenic switch, Prdm16 (BL: 1.8±1.9 vs 6M: 4.5±4.1, p&amp;lt; 0.01); Pax7 (BL:1.3±0.8 vs 6M: 1.9±2.0, p=0.2) in buffy coat. T therapy also increased serum Follistatin (BL:2031±1483 vs 6M: 3396 ± 1662pg/ml, p=0.009), the myogenic regulator, PAX7 (BL:21.5±1.9 vs 6M: 34±2.2ng/ml, p=0.002); and PRDM16 (BL:0.20±0.10 vs 6M: 0.49±0.26ng/ml, p=0.29) and decreased serum Myostatin (BL: 3218±738 vs 6M: 2714±62.2pg/ml, p=0.42) Adipsin (BL:15929±10209 vs 6M:12101±4865ng/ml p=0.04). COPs increased in T-treated (T) compared to Placebo (P); (P (6M): -4.3±57 vs T(6M): -20.2±44, p=0.20 &amp; P(12M): -15.7±44.5 vs T(12M): 47.4±74.8, p=0.02)) and Runx2 expression increased (BL: 1.26±0.86 vs 6M: 2.17±1.6, p=0.03). Conclusions: Our results suggested that reciprocal effect of T-therapy on fat mass and lean mass is not only due to shift from adipogenesis to myogenesis but also due to enhanced osteogenesis. Thus, this study can provide unifying mechanism for observed effect of T in hypogonadal men. Presentation Date: Saturday, June 17, 2023

The effect of fat distribution and nutritional behavior on balance and equilibrium of acrobatics and tumbling athletes

Acrobatics and Tumbling (A&amp;T) is an emerging sport in the United States; balance and equilibrium are critical components of performance in this sport. Therefore, the aim of this study was to identify if body composition, fat distribution, and nutritional behavior affect the balance and vertical jump of A&amp;T athletes. Body mass index (BMI), whole body percentage of fat and skeletal muscle, and fat distribution of top and base A&amp;T athletes from Fairmont State University were assessed using an impedance device (In Body 570). Nutritional behavior was assessed by a 3-day food log. Balance was measured by the time of holding a handstand in seconds. BMI, whole body, and truncal fat percentage were higher in base athletes when compared to tops (p˂0.05). When associating balance with the variables, skeletal muscle mass was positively associated with balance (r=0.49, p˂0.05), and the percentage of fat and fat accumulation in the lower limbs were negatively associated (r=-0.47 and -0.48, respectively p˂0.05). When the association was tested within the position, the percentage of skeletal muscle mass and fat was only associated with balance in top athletes. Thus, training strategies to increment skeletal muscle mass and decrease body fat should be the focus to improve the balance of top A&amp;T athletes.