Subcutaneous Adipose Tissue Mass Research Articles

Gain and loss of subcutaneous and abdominal adipose tissue depot mass of German Holstein dairy cows with different body conditions during the transition period

Subcutaneous adipose tissue (SCAT) and abdominal adipose tissue (AAT) depots are mobilized during the fresh cow period (FCP) and early lactation period (ELP) to counteract the negative energy balance (NEB). Earlier studies suggested that fat depots contribute differently to lipomobilization and may vary in functionality. Differences between the adipose depots might influence the development of metabolic disorders. Thus, the gain and loss of subcutaneous and abdominal adipose depot masses in Holstein cows with lower and higher body condition (mean body condition scores: 3.48 and 3.87, respectively) were compared in the period from d -42 to d 70 relative to parturition in this study. Animals of the 2 experimental groups represented adequately conditioned and overconditioned cows. Estimated depot mass (eDM) of SCAT, AAT, retroperitoneal, omental, and mesenteric adipose depots of 31 pluriparous German Holstein cows were determined via ultrasonography at d -42, 7, 28, and 70 relative to parturition. The cows were grouped according to the eDM of SCAT on d -42 [low body condition (LBC) group: n = 16, mean eDM 8.6 kg; high body condition (HBC) group: n = 15, mean eDM 15.6 kg]. Average daily change (prepartum gain and postpartum loss) in depot masses during dry period (DP; from d -42 to d 7), FCP (d 7 to d 28), and ELP (d 28 to d 70) were calculated and daily dry matter intake and lactation performance recorded. Cows of this study stored about 2 to 3 times more fat in AAT than in SCAT depots. After parturition, on average more adipose tissue mass was lost from the AAT than the SCAT depot (0.23 kg/d vs. 0.14 kg/d). Cows with high compared with low body condition had similar gains in AAT (0.33 kg/d) and SCAT (0.14 kg/d) masses during the DP but mobilized significantly more adipose tissue mass from both depots after calving (AAT, HBC vs. LBC: 0.30 vs. 0.17 kg/d; SCAT, HBC vs. LBC: 0.19 vs. 0.10 kg/d). Correlation analysis indicated a functional disparity between AAT and SCAT. In the case of AAT (R2 = 0.36), the higher the gain in adipose mass during DP, the higher the loss in FCP, but this was not the case for SCAT. During FCP, a greater NEB resulted in greater loss of mass from SCAT (R2 = 0.18). In turn, greater mobilization of SCAT mass led to a higher calculated feed efficiency (R2 = 0.18). However, AAT showed no such correlations. On the other hand, during ELP, loss of both SCAT and AAT mass correlated positively with feed efficiency (R2 = 0.35 and 0.33, respectively). The results indicate that feed efficiency may not be an adequate criterion for performance evaluation in cows during NEB. Greater knowledge of functional disparities between AAT and SCAT depots may improve our understanding of excessive lipomobilization and its consequences for metabolic health and performance of dairy cows during the transition period.

Ultrasound method of the USVALID study to measure subcutaneous adipose tissue and muscle thickness on the thigh and upper arm: An illustrated step-by-step guide

Summary Objective So far there is no standardised widely accepted ultrasound method for assessment of both subcutaneous adipose tissue and muscle mass in healthy subjects, patients and ICU patients. The goal is to provide an illustrated step-by-step guide of the ultrasound method developed since 2011, refined and applied during the USVALID study. Methods We use 2 linear probes with a footprint width of 25,6 and 38,4 mm. The subject is lying relaxed with the head of bed elevated to 30°. Foam supports are placed under elbows and knees. Precise anatomical landmarks are palpated to measure the limb lengths. 3 measuring points at 50% of the thigh length and 2 measuring points at 70% of the upper arm length are marked on both sides. A gelpad is used to enable minimal compression. It is verified that the borders of the scan are blurred. Each measuring point is scanned in the short-axis and long-axis plane to more easily determine the subcutaneous adipose tissue and muscle structures especially in the presence of edema. First the quality of the scan is evaluated according to the visibility of the muscle fascia and bone surface. Then subcutaneous adipose tissue and entire muscle thickness are measured at the exact center of the scan drawing the shortest possible line from skin to bone surface. Discussion The illustrated description of the USVALID ultrasound method enables reproducibility by other researchers for external validity. The subject's position, the location of the measuring points, the performance and evaluation of the ultrasound scans are discussed and compared to other published ultrasound methodologies.

Effects of High-Intensity Exercise Training on Adipose Tissue Mass, Glucose Uptake and Protein Content in Pre- and Post-menopausal Women.

The menopausal transition is accompanied by changes in adipose tissue storage, leading to an android body composition associated with increased risk of type 2 diabetes and cardiovascular disease in post-menopausal women. Estrogens probably affect local adipose tissue depots differently. We investigated how menopausal status and exercise training influence adipose tissue mass, adipose tissue insulin sensitivity and adipose tissue proteins associated with lipogenesis/lipolysis and mitochondrial function. Healthy, normal-weight pre- (n = 21) and post-menopausal (n = 20) women participated in high-intensity exercise training three times per week for 12 weeks. Adipose tissue distribution was determined by dual-energy x-ray absorptiometry and magnetic resonance imaging. Adipose tissue glucose uptake was assessed by positron emission tomography/computed tomography (PET/CT) by the glucose analog [18F]fluorodeoxyglucose ([18F]FDG) during continuous insulin infusion (40 mU·m−2·min−1). Protein content associated with insulin signaling, lipogenesis/lipolysis, and mitochondrial function were determined by western blotting in abdominal and femoral white adipose tissue biopsies. The mean age difference between the pre- and the post-menopausal women was 4.5 years. Exercise training reduced subcutaneous (~4%) and visceral (~6%) adipose tissue masses similarly in pre- and post-menopausal women. Insulin-stimulated glucose uptake, assessed by [18F]FDG-uptake during PET/CT, was similar in pre- and post-menopausal women in abdominal, gluteal, and femoral adipose tissue depots, despite skeletal muscle insulin resistance in post- compared to pre-menopausal women in the same cohort. Insulin-stimulated glucose uptake in adipose tissue depots was not changed after 3 months of high-intensity exercise training, but insulin sensitivity was higher in visceral compared to subcutaneous adipose tissue depots (~139%). Post-menopausal women exhibited increased hexokinase and adipose triglyceride lipase content in subcutaneous abdominal adipose tissue. Physical activity in the early post-menopausal years reduces abdominal obesity, but insulin sensitivity of adipose tissue seems unaffected by both menopausal status and physical activity.

Obesity Phenotypes, Diabetes, and Cardiovascular Diseases

This review addresses the interplay between obesity, type 2 diabetes mellitus, and cardiovascular diseases. It is proposed that obesity, generally defined by an excess of body fat causing prejudice to health, can no longer be evaluated solely by the body mass index (expressed in kg/m2) because it represents a heterogeneous entity. For instance, several cardiometabolic imaging studies have shown that some individuals who have a normal weight or who are overweight are at high risk if they have an excess of visceral adipose tissue-a condition often accompanied by accumulation of fat in normally lean tissues (ectopic fat deposition in liver, heart, skeletal muscle, etc). On the other hand, individuals who are overweight or obese can nevertheless be at much lower risk than expected when faced with excess energy intake if they have the ability to expand their subcutaneous adipose tissue mass, particularly in the gluteal-femoral area. Hence, excessive amounts of visceral adipose tissue and of ectopic fat largely define the cardiovascular disease risk of overweight and moderate obesity. There is also a rapidly expanding subgroup of patients characterized by a high accumulation of body fat (severe obesity). Severe obesity is characterized by specific additional cardiovascular health issues that should receive attention. Because of the difficulties of normalizing body fat content in patients with severe obesity, more aggressive treatments have been studied in this subgroup of individuals such as obesity surgery, also referred to as metabolic surgery. On the basis of the above, we propose that we should refer to obesities rather than obesity.

SUN-LB106 The Transcriptomic Evidences on Role of Abdominal Visceral vs. Subcutaneous Adipose Tissue in the Pathophysiology of Diabetes in Asian Indian Indicates the Involvement of Both

Introduction: Asian Indians show “thin fat phenotype” characterized by higher visceral adipose tissue(VAT) and lower subcutaneous adipose tissue(SAT) mass and their higher cardio-metabolic risk has been attributed to this fat distribution. However, the underlying molecular pathology and role of these adipose depots in the pathogenesis of T2D in them remains unknown.Hypothesis: The comparison of transcription profiles of abdominal VAT and SAT and their correlation with diabetes related intermediate phenotypic traits could shed some light on their role in the pathophysiology of diabetes.MethodologySubjects: 19 diabetics (M: F ratio, 8:11) and 16 age and BMI matched controls (M: F ratio 5:11) undergoing abdominal surgery (non-malignant and non-infective conditions).Clinical Parameters: Anthropometry, Serum glucose, insulin, HOMA-R, HbA1c, lipid profile, FFA, adipocytokines. Abdominal VAT, SAT and liver fat were estimated by MRI.Adipose tissue biopsy: SAT and VAT samples were taken during surgery. Genome-wide gene expression profiling of these biopsies was performed using Affymetrix GeneChipPrimeView® arrays. The data was submitted to NCBI-GEO (Accession # GSE78721). Selected genes were validated by qPCR. Gene set enrichment analysis (GSEA) for functional and Weighted Gene Correlation Analysis (WGCNA) for statistical comparison was done.Results:Diabetics had higher waist circumference (p=0.05), HOMA-R (p=0.0002), Visceral fat content (p=0.02) and adipocyte size (p=0.02)GSEA: diabetics vs. controls: In VAT 16 gene sets were upregulated (FDR < 25%) enriching various immune system and inflammation-related pathways. In SAT too, various inflammatory genes were upregulated however they were statistically non-significant (FDR > 25%). Moreover, 12 out of 16 significantly enriched pathways in VAT were among the top 20 pathways in SAT. GSEA in diabetics: VAT vs SAT: None of the gene sets were found significant at FDR < 25% which substantiated our hypothesis that overall pathophysioloigcal alteration in both depots are similar. WGCNA for statistical comparison of VAT and SAT depots The correlation between measures of average gene expression and overall connectivity between both depots was significantly positive. Several modules of co-expressed genes in both VAT and SAT showed positive as well as negative correlation with various intermediate phenotypic traits of diabetes. In both depots they enriched several pathways otherwise known to be associated with pathological adipose tissue like inflammation, adipogenesis etc.ConclusionsIn Asian Indians, diabetes pathology inflicts similar molecular alternations in VAT and SAT, which are more intense in the former. The role of both adipose depots in the pathophysiology of diabetes is along similar lines and they enrich several molecular pathways which are otherwise known to be implicated in pathological adipose tissue.

Expression profiling and analysis of some miRNAs in subcutaneous white adipose tissue during development of obesity

BackgroundMicroRNAs are emerging as new mediators in the regulation of adipocyte physiology and have been approved to play a role in obesity. Despite several studies have focused on microRNA expression profiles and functions in different metabolic tissues, little is known about their response to nutritional interventions in white adipose tissue during obesity stages, and whether they differ in this response to weight-reduction strategy is poorly understood. Our objectives were to study the dysregulation of some miRNAs in subcutaneous inguinal white adipose tissue during weight change, expansion/reduction; in response to both a high-fat diet and switching to a normal diet feeding, and to evaluate them as potential biomarkers and therapeutic targets for early obesity managementMethodA hundred 6-week-old male Wister rats were randomly divided into a normal diet group (N.D), a high-fat diet group (H.F.D), and a switched to a normal diet group (H.F.D/N.D). At the beginning and at intervals 2 weeks, serum lipid, hormone levels, total body fat mass, and inguinal subcutaneous white adipose tissue mass (WAT) measurements were recorded using dual-energy X-ray absorptiometry (DEXA). The expression levels of microRNAs were evaluated using real-time PCR.ResultsSignificant alterations were observed in serum glucose, lipid profile, and adipokine hormones during the early stages of obesity development. Alteration in rno-mir 30a-5p, rno-mir 133a-5p, and rno-mir 107-5p expression levels were observed at more than one time point. While rno-let-7a-5p, rno-mir 193a-5p, and rno-mir125a-5p were downregulated and rno-mir130a-5p was upregulated at all time points within 2 to 4 weeks in response to H.F.D feeding for 10 weeks. The impact of switching to normal diet has a reversed effect on lipid profile, adipokine hormone levels, and some miRNAs. The bioinformatics results have identified a novel and important pathway related to inflammatory signalling.ConclusionOur research demonstrated significant alterations in some adipocyte-expressed miRNAs after a short time of high caloric diet consumption. This provides further evidence of the significant role of nutrition as an epigenetic factor in regulation of lipid and glucose metabolism genes by modulating of related key miRNAs. Therefore, we suggest that miRNAs could be used as biomarkers for adiposity during diet-induced obesity. Perhaps limitation in calories intake is a way to manipulate obesity and associated metabolic disorders. Further studies are needed to fully elucidate the role of microRNAs in the development of obesity

Long-term hypercortisolism induces lipogenesis promoting palmitic acid accumulation and inflammation in visceral adipose tissue compared with HFD-induced obesity.

Glucocorticoids (GCs) play critical roles in adipose tissue metabolism. Here, we compare in a mouse model the effects of chronic glucocorticoid excess and diet-induced obesity on white adipose tissue mass and distribution, by focusing on visceral adipose tissue (VAT) fatty acid composition changes, the role of de novo lipogenesis (DNL) and the inflammatory state. We used a noninvasive mouse model of hypercortisolism to compare GC-induced effects on adipose tissue with diet-induced obesity [high-fat diet (HFD) 45%] and control mice after 10 wk of treatment. Subcutaneous adipose tissue (SAT) and VAT mass and distribution were measured by nuclear magnetic resonance imaging (NMRI). Fatty acid composition in VAT was analyzed by NMR spectroscopy and gas chromatography. Gene expression of key enzymes involved in DNL was analyzed in liver and VAT. Macrophage infiltration markers and proinflammatory cytokines were measured by gene expression in VAT. HFD or GC treatment induced similar fat mass expansion with comparable distribution between SAT and VAT depots. However, in VAT, GCs induce DNL, higher palmitic acid (PA), macrophage infiltration, and proinflammatory cytokine levels, accompanied by systemic nonesterified fatty acid (NEFA) elevation, hyperinsulinemia, and higher homeostatic model assessment for insulin resistance (HOMA-IR) levels compared with diet-induced obesity. Thus, chronic hypercortisolism induces DNL and fatty acid composition changes toward increased SFA and reduced polyunsaturated fatty acid (PUFA) levels in VAT, promoting macrophage recruitment and proinflammatory cytokines, suggesting a worse cardiometabolic profile even compared with HFD mice.

Artificial sweeteners impair endothelial vascular reactivity: Preliminary results in rodents

Background and aimsProspective epidemiological studies highlighted recently the link between artificial sweeteners (AS) consumption and the risk of developing cardiometabolic diseases. However, underlying mechanisms remain unknown. Thus, the aim of this preliminary study was to characterize, in a healthy rat population, the effect of chronic AS consumption on body composition and vascular function, an early marker for cardiovascular disease. Methods and resultsHealthy Wistar rats followed a 10-week standard diet including the consumption of water sweetened or not with a sucralose/acesulfame potassium solution at different concentrations: for moderate consumption at 1 and 2 mg.kg−1.day−1, respectively or high intake at 15 and 15 mg.kg−1.day−1 for both molecules (acceptable daily intake). Body fat composition has been evaluated and ex vivo aortic vasomotor function has been investigated with a pharmacological approach. ConclusionBoth groups of AS-treated rats showed a significant increase in subcutaneous and perirenal adipose tissue mass storage, without changes in total body mass. However, rats that have consumed AS at Acceptable Daily Intake (ADI) concentration revealed a significant vascular endothelial dysfunction compared to other groups. These results are interesting because they will help to better explain the observed increase in cardiometabolic risk.

Chronic arsenic exposure impairs adaptive thermogenesis in male C57BL/6J mice.

The global prevalence of type 2 diabetes (T2D) has doubled since 1980. Human epidemiological studies support arsenic exposure as a risk factor for T2D, although the precise mechanism is unclear. We hypothesized that chronic arsenic ingestion alters glucose homeostasis by impairing adaptive thermogenesis, i.e., body heat production in cold environments. Arsenic is a pervasive environmental contaminant, with more than 200 million people worldwide currently exposed to arsenic-contaminated drinking water. Male C57BL/6J mice exposed to sodium arsenite in drinking water at 300 μg/L for 9 wk experienced significantly decreased metabolic heat production when acclimated to chronic cold tolerance testing, as evidenced by indirect calorimetry, despite no change in physical activity. Arsenic exposure increased total fat mass and subcutaneous inguinal white adipose tissue (iWAT) mass. RNA sequencing analysis of iWAT indicated that arsenic dysregulated mitochondrial processes, including fatty acid metabolism. Western blotting in WAT confirmed that arsenic significantly decreased TOMM20, a correlate of mitochondrial abundance; PGC1A, a master regulator of mitochondrial biogenesis; and, CPT1B, the rate-limiting step of fatty acid oxidation (FAO). Our findings show that chronic arsenic exposure impacts the mitochondrial proteins of thermogenic tissues involved in energy expenditure and substrate regulation, providing novel mechanistic evidence for arsenic's role in T2D development.

Visceral Adipose Tissue Radiodensity Is Linked to Prognosis in Hepatocellular Carcinoma Patients Treated with Selective Internal Radiation Therapy.

Hepatocellular carcinoma (HCC) constitutes the fourth leading cause of cancer-related mortality. Various factors, such as tumor size, tumor multiplicity, and liver function, have been linked to the prognosis of HCC. The aim of this study was to explore the prognostic significance of muscle, subcutaneous and visceral adipose tissue (VAT) mass, and radiodensity, in a cohort of 101 HCC patients treated with selective internal radiation therapy (SIRT). Muscle and adipose tissue cross sectional area (cm2/m2) and radiodensity, reported as the Hounsfield Unit (HU), were determined using pre-SIRT computed tomography images. Cox proportional hazard models and exact logistic regression were conducted to assess associations between body composition and adverse outcomes. Majority of the patients were male (88%) with a mean VAT radiodensity of −85 ± 9 HU. VAT radiodensity was independently associated with mortality (HR 1.05; 95% CI: 1.01–1.08; p = 0.01), after adjusting for cirrhosis etiology, Barcelona Clinic Liver Cancer stage, previous HCC treatment, and portal hypertension markers. Patients with a high VAT radiodensity of ≥–85 HU had a two times higher risk of mortality (HR 2.01, 95% CI 1.14–3.54, p = 0.02), compared to their counterpart. Clinical features of portal hypertension were more prevalent in patients with high VAT radiodensity. High VAT radiodensity was associated with severe adverse events after adjusting for confounding factors. High VAT radiodensity is independently associated with both increased mortality and severe adverse events in patients treated with SIRT. VAT radiodensity measurement might serve as an objective approach to identify patients who will experience the most benefit from SIRT.

Computed Tomography-Based Body Composition Is Not Consistently Associated with Outcome in Older Patients with Colorectal Cancer.

BackgroundCurrent literature is inconsistent in the associations between computed tomography (CT)‐based body composition measures and adverse outcomes in older patients with colorectal cancer (CRC). Moreover, the associations with consecutive treatment modalities have not been studied. This study compared the associations of CT‐based body composition measures with surgery‐ and chemotherapy‐related complications and survival in older patients with CRC.Materials and MethodsA retrospective single‐center cohort study was conducted in patients with CRC aged ≥65 years who underwent elective surgery between 2010 and 2014. Gender‐specific standardized scores of preoperative CT‐based skeletal muscle (SM), muscle density, intermuscular adipose tissue (IMAT), visceral adipose tissue (VAT), subcutaneous adipose tissue, IMAT percentage, SM/VAT, and body mass index (BMI) were tested for their associations with severe postoperative complications, prolonged length of stay (LOS), readmission, and dose‐limiting toxicity using logistic regression and 1‐year and long‐term survival (range 3.7–6.6 years) using Cox regression. Bonferroni correction was applied to account for multiple testing.ResultsThe study population consisted of 378 patients with CRC with a median age of 73.4 (interquartile range 69.5–78.4) years. Severe postoperative complications occurred in 13.0%, and 39.4% of patients died during follow‐up. Dose‐limiting toxicity occurred in 77.4% of patients receiving chemotherapy (n = 53). SM, muscle density, VAT, SM/VAT, and BMI were associated with surgery‐related complications, and muscle density, IMAT, IMAT percentage, and SM/VAT were associated with long‐term survival. After Bonferroni correction, no CT‐based body composition measure was significantly associated with adverse outcomes. Higher BMI was associated with prolonged LOS.ConclusionThe associations between CT‐based body composition measures and adverse outcomes of consecutive treatment modalities in older patients with CRC were not consistent or statistically significant.Implications for PracticeComputed tomography (CT)‐based body composition, including muscle mass, muscle density, and intermuscular, visceral, and subcutaneous adipose tissue, showed inconsistent and nonsignificant associations with surgery‐related complications, dose‐limiting toxicity, and overall survival in older adults with colorectal cancer. This study underscores the need to verify whether CT‐based body composition measures are worth implementing in clinical practice.

ACE2 exerts anti-obesity effect via stimulating brown adipose tissue and induction of browning in white adipose tissue.

The angiotensin II (ANG II)-ANG II type 1 receptor (AT1R) axis is a key player in the pathophysiology of obesity. Angiotensin-converting enzyme 2 (ACE2) counteracts the ANG II/AT1R axis via converting ANG II to angiotensin 1-7 (Ang 1-7), which is known to have an anti-obesity effect. In this study, we hypothesized that ACE2 exerts a strong anti-obesity effect by increasing Ang 1-7 levels. We injected intraperitoneally recombinant human ACE2 (rhACE2, 2.0 mg·kg-1·day-1) for 28 days to high-fat diet (HFD)-induced obesity mice. rhACE2 treatment decreased body weight and improved glucose metabolism. Furthermore, rhACE2 increased oxygen consumption and upregulated thermogenesis in HFD-fed mice. In the rhACE2 treatment group, brown adipose tissue (BAT) mass increased, accompanied with ameliorated insulin signaling and increased protein levels of uncoupling protein-1 (UCP-1) and PRD1-BF1-RIZ1 homologous domain containing 16. Importantly, subcutaneous white adipose tissue (sWAT) mass decreased, concomitant with browning, which was established by the increase of UCP-1 expression. The browning is the result of increased H3K27 acetylation via the downregulation of histone deacetylase 3 and increased H3K9 acetylation via upregulation of GCN5 and P300/CBP-associated factor. These results suggest that rhACE2 exerts anti-obesity effects by stimulating BAT and inducing browning in sWAT. ACE2 and the Ang 1-7 axis represent a potential therapeutic approach to prevent the development of obesity.

Fatigue, quality of life and metabolic changes in men treated with first-line enzalutamide versus abiraterone plus prednisolone for metastatic castration-resistant prostate cancer (HEAT): a randomised trial protocol

IntroductionEnzalutamide and abiraterone acetate plus prednisolone (AAP) are used in combination with androgen-deprivation therapy to further suppress the androgen stimulation of metastatic castration-resistant prostate cancer (mCRPC). First-line mCRPC treatment with...

A Possible Mechanism: Genistein Improves Metabolism and Induces White Fat Browning Through Modulating Hypothalamic Expression of Ucn3, Depp, and Stc1.

Bioactive food components have gained growing attention in recent years. Multiple studies demonstrated that genistein had beneficial effects on metabolism. However, the exact mechanism by which genistein improves metabolism remains unclear, especially the central regulation. This study was designed to evaluate whether addition of genistein to the high-fat diet could counter metabolic disorders and whether these alterations were associated with gene expression in hypothalamus. C57BL/6 mice were fed either a high-fat diet (HF), high-fat diet with genistein (0.25 g/kg diet) (HFG) or a normal control diet (CON) for 8 weeks. Body weight was assessed during the study. After 8-week intervention, content of inguinal subcutaneous adipose tissue (SAT), perirenal visceral adipose tissue (VAT) and brown adipose tissue (BAT) were weighed. Glucose tolerance test, the serum levels of insulin and lipid were assessed. The mRNA of browning marker was detected in the white fat. The hypothalamus was collected for whole transcriptome sequencing and reverse transcription quantitative PCR validation. The results demonstrated that mice fed HFG diet had lower body weight and SAT mass, decrease levels of low-density lipoprotein cholesterol and free fatty acids, higher browning marker of Ucp1 and Cidea in WAT and an improvement in glucose tolerance and insulin sensitivity compared with those in HF group. Transcriptome sequencing showed that there were three differentially expressed genes in hypothalamus among the three groups, including Ucn3, Depp, and Stc1, which were significantly correlated with the browning markers in WAT and insulin sensitivity. Thus, regulating gene expressions in hypothalamus is a potential mechanism for genistein improving metabolism and inducing WAT browning, which may provide a novel target for the precaution and treatment of T2DM.

Evaluation of Preoperative Abdominal Adipose Tissue–, Inflammation-, Muscle Mass–, and Nutritional Status–based Prognostic Markers to Assess Renal Dysfunction in Living Kidney Donors

BackgroundLiving kidney donors (LKDs) are at high risk of renal dysfunction after undergoing a donor nephrectomy (DN), resulting in poor prognosis associated with the development of cardiovascular or cerebrovascular disease. Decreasing this risk can improve the survival rate of LKDs. We investigated the effects of preoperative conditions in LKDs on renal dysfunction after DN using abdominal adipose tissue, inflammation, nutritional status, and muscle mass as markers for this assessment. MethodsOur retrospective study included 79 LKDs. Body composition markers were assessed using preoperative unenhanced computed tomographic images. Inflammation- and nutritional status–based markers were assessed using preoperative laboratory blood tests. The association between each marker was investigated, and prognostic markers for renal dysfunction after DN were identified. ResultsThe LKDs in this cohort comprised 30 men and 49 women. The median age at the time of DN and the preoperative estimated glomerular filtration rate were 58 years and 81.9 mL/min/1.73 m2, respectively. Abdominal subcutaneous adipose tissue and muscle mass significantly differed between the sexes. Each adipose tissue–, inflammation-, nutritional status–, and muscle mass–based marker showed an association with each other. Abdominal visceral adipose tissue and nutritional status could be independent prognostic markers for renal dysfunction after DN. ConclusionsOur findings suggest that the preoperative condition of LKDs (assessed using specific markers such as abdominal visceral adipose tissue mass per volume and nutritional status) could affect renal dysfunction after DN. Optimal preoperative management can lead to better outcomes in LKDs. Further research is needed to establish appropriate exercise programs and nutritional interventions.

1821-P: A Possible Mechanism: Genistein Improves Metabolism and Induces White Fat Browning through Modulating Hypothalamic Expression of Ucn3, Depp, and Stc1

Bioactive food components have gained growing attention in recent years. Multitude of studies have demonstrated that genistein, as a soy-derived phytoestrogen, has beneficial effects on metabolism. However, the exact mechanism by which genistein improving metabolic disorders remains unclear, especially the central regulation. This study was designed to evaluate whether addition of genistein to the high-fat diet could counter the metabolic disorders and whether these alterations were associated with the gene expression in hypothalamus. C57BL/6 mice were fed either a high-fat diet (HF), high-fat diet with genistein (0.25g/kg diet) (HFG) or a normal control diet (CON) for eight weeks. Body weight were assessed during the study. After eight-week intervention, content of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and brown adipose tissue (BAT) were weighed. Glucose tolerance test, the serum levels of insulin and lipid were assessed. The mRNA of browning marker was detected in the WAT. The hypothalamus was collected for whole transcriptome sequencing and reverse transcription quantitative PCR (RT-qPCR) validation. The results demonstrated that mice fed the HFG diet had lower body weight (p&amp;lt;0.05) and SAT mass (p&amp;lt;0.01), decrease levels of low-density lipoprotein cholesterol (LDL-C) (p&amp;lt;0.01) and free fatty acids (FFA) (p&amp;lt;0.05), higher browning marker of Ucp1 (p&amp;lt;0.01) and Cidea (p&amp;lt;0.05) in WAT and an improvement in glucose tolerance and insulin sensitivity compared with those in the HF group. Transcriptome sequencing showed that there were three differentially expressed genes in hypothalamus among the three groups, including Ucn3 (p&amp;lt;0.05), Depp (p&amp;lt;0.01) and Stc1 (p&amp;lt;0.01). Thus, regulating gene expressions in hypothalamus is a potential mechanism for genistien improving metabolism and inducing WAT browning, which may provide a novel target for the precaution and treatment of T2DM. Disclosure L. Zhou: None. X. Xiao: None. M. Deng: None. J. Liu: None. M. Yu: None. Funding National Natural Science Foundation of China

Essential Fatty Acid Deficiency (EFAD) in a Patient with Vascular Ehlers Danlos Syndrome (EDS-4) (P12-053-19)

ObjectivesEDS-4 comprises ∼4% of all EDS, involving mutations in type III procollagen rather than type V. It causes spontaneous vascular and visceral rupture but not large joint or skin hypermotility. Nutritional deficiencies and malabsorption have been described in classical EDS, but not in EDS-4. MethodsA 30-year-old female with EDS-4, bowel obstruction, spontaneous colon rupture, spontaneous pneumothorax and cholecystitis had fatigue, diarrhea, abdominal pain, hair loss and dry skin. Stools were malodorous and floating; oily and often orange in color. There was no response to bile acid sequestration.The patient weighed 40.4 KG (BMI = 16.9) with intact muscle mass and near total absence of subcutaneous adipose tissue. There were sparse hair follicles; hair was easily pluckable and lanugo-like. The skin was thin and translucent; dry with flaking and peeling both tibial regions.Vitamin levels (A, D, E, K1, C, B1, B6, B9, B12) were normal as were zinc, iron, copper and carnitine. Levels of palmitoleic (C16:1w7), hexadecenoic (C16:1w9), linoleic (C18:2w6), alpha linolenic (C18:3w3), gamma linolenic (C18:3w6), vaccenic (C18:3w7), arachidic (C20:0), arachidonic (C20:4w6), docosenoic (C22:1) and nervoic (C24:1w9) acids were deficient. The triene-tetraene ratio was 0.028 (range = 0.01–0.038). ResultsWe diagnosed fat malabsorption (FM) with EFAD and began pancreatic enzyme replacement with a blend of vegetable oils (coconut, corn, soy, safflower, olive and avocado). After 6 months, there was reversal of all deficiencies. GI symptoms, general strength and vitality improved. Her scalp hair increased. The hair shafts were less fragile and normal in color. The skin dryness, flaking and peeling had resolved. ConclusionsEDS-4 patients may present with FM and develop EFAD. The pathogenensis of FM in EDS-4 may involve disordered collagen type III within the bowel wall, pancreatic matrix or ductal system. Dysbiosis and dysautonomia may also play a role. The combination of pancreatic enzyme replacement and fatty acid supplementation was beneficial in this case and may be appropriate for other patients with EDS-4 and FM. Funding Sourcesnone.

SAT-438 Visceral and Marrow Adiposity in Patients with Acromegaly; Relationships to Disease Activity, Markers of Bone Turnover, Bone Mineral Density, and Peripheral Bone Microarchitecture

Adipose tissue (AT) mass, especially visceral (VAT), is reduced in active acromegaly and rises with treatment. Although the effect of acromegaly and its therapy on marrow AT(MAT) is unknown, data in other populations and in vitro, suggest a reciprocal relationship between GH and marrow adiposity. In other groups, VAT and MAT are associated with reduced bone quality and increased vertebral fracture (VF) risk. Therefore, since acromegaly patients have an increased VF incidence, we examined the relationships of VAT and MAT to bone quality in acromegaly. We studied 65 acromegaly subjects (40 men, 25 women, range 18.7-74 yr.) before (n=20) or before and after (n=45) acromegaly therapy by total body multi-slice MRI(n=159)(measurement of VAT, subcutaneous (SAT) and total (TAT) adipose tissue mass), DXA (BMD (n=120) and body composition (n=145)) and HRpQCT (n=35) (microarchitecture of the tibia and radius). Marrow lipid spectra of the tibial diaphysis were acquired by 1H MRS (PRESS technique)(1.5T MR scanner, Philips) and percentages of bone marrow lipids were quantified (n=53). GH and IGF-1 (n=159) and bone turnover markers (BTM)(n=49) were measured. We examined the relationship between MAT or VAT and GH, IGF-1, age, weight, mass of other MRI measured AT depots, and selected DXA and HRpQCT parameters previously shown to differ in acromegaly compared to healthy subjects and to be associated in other groups with fracture. Data were analyzed by Pearson correlation and the generalized estimating equation (GEE). MAT directly correlated with VAT (r=.249, p=.023) and by HRpQCT (n=13) with bone size (radius: total area (r=.678, p=.01), tibia: total area (r=.535, p=.05)) and trabecular number (r=.543, p=.055). VAT was inversely associated with GH (β= -.017, p<.001), IGF-1 level (expressed as % upper normal limit) (β= -0.004, p=.049) and BTMs (N-Mid Osteocalcin (β= -.0223, p<0.001); CTX (β= -.7283, p=.0134)). VAT was positively associated with age (β=.034, p=.053), weight (β=.072, p <.0001) and with HRpQCT measured bone size (radius: total area (β=.0073, p=.0098); tibia: total area (β= .0049, p <.0001)) and trabecular number (tibia: β=1.9321, p=.0096), and inversely associated with cortical thickness (radius: β= -2.8477, p= .074; tibia: β= -2.3341, p=.0497), trabecular thickness (tibia: β= -92, p<.0001) and total body density (radius β= -.0102, p=.0353; tibia: β= -.0149, p=.003). In summary, VAT is inversely related to acromegaly disease activity, consistent with its known rise as acromegaly is treated. We found that greater VAT is associated with larger bone size and lower bone turnover, but also with some less favorable aspects of bone microarchitecture. MAT correlated with VAT and, in a small number of subjects, with bone size. Whether rising adiposity and reductions in bone turnover with acromegaly therapy are relevant to the skeletal fragility reported in treated acromegaly warrants further study.

Novel approaches for the assessment of relative body weight and body fat in diagnosis and treatment of anorexia nervosa: A cross-sectional study

Anorexia nervosa (AN) is a severe psychosomatic disease that seriously affects nutritional status. Therapeutic approaches primarily aim for rapid weight restoration by high caloric diets and activity restriction. This often promotes abdominal body fat gain, which potentially negatively influences the patient's compliance and increases the risk of relapse. This study focused on the evaluation of body weight and subcutaneous adipose tissue (SAT) in AN patients by novel approaches. The SAT of AN patients (n=18, body mass index (BMI) 15.3±1.3kg/m2) was determined by a highly accurate and reliable ultrasound method. The sum of SAT thicknesses of eight sites (DINCL) was calculated. Individual metabolic profiles were analyzed. The mass index (MI), which considers body proportions, was used in addition to BMI. Additional to the standard laboratory diagnostics, dermal carotenoids measured by resonance Raman spectroscopy, leptin, and oxidative stress indicators were determined. The mean MI was 15.7±1.4kg/m2. The DINCL considerably differed between individuals with the same BMI. Half of the patients (Group 1) had low DINCL: 1.3-28.4mm, and Group 2 showed values up to 58.2mm (corresponding to approximately 6kg SAT mass). The two group means differed by more than 300% (P < 0.001). Accordingly, leptin levels significantly differed (P < 0.001). Mean SAT thicknesses were significantly higher in Group 2at all eight sites. The groups also significantly differed in two oxidative stress parameters: total antioxidative capacity, malondialdehyde-modified low density lipoprotein immunoglobulin M (MDA-LDL IgM), and in the carotenoid level. Half of the patients had sufficiently high fat mass, despite very low BMI. Consequently, their muscle (and other organ) masses must have been extremely low. Diagnostic criteria and treatment protocols for AN should consider each patient's body composition. In addition to dietary treatments, muscle training at low energy turnover rates may be essential for avoiding unnecessary body fat gain, better treatment results, and long-term recovery.

Prediction of Circulating Adipokine Levels Based on Body Fat Compartments and Adipose Tissue Gene Expression

Background: Adipokines are hormones secreted from adipose tissue (AT), and a number of them have been established as risk factors for chronic diseases. However, it is not clear whether and to what extent adiposity, gene expression, and other factors determine their circulating levels. Objectives: To assess to what extent adiposity, as measured by the amount of subcutaneous AT (SAT) and visceral AT (VAT) using magnetic resonance imaging, and gene expression levels in SAT determine plasma concentrations of the adipokines adiponectin, leptin, soluble leptin receptor, resistin, interleukin 6, and fatty acid-binding protein 4 (FABP4). Methods: We performed a cross-sectional analysis of 156 participants from the EPIC Potsdam cohort study and analyzed multiple regression models and partial correlation coefficients. Results: For leptin and FABP4 concentrations, 81 and 45% variance were explained by SAT mass, VAT mass, and gene expression in SAT in multivariable regression models. For the remaining adipokines, AT mass and gene expression explained <16% variance of plasma concentrations. Gene expression in SAT was a less important predictor compared to AT mass. SAT mass was a better predictor than VAT mass for leptin (partial correlation r = 0.81, 95% confidence interval 0.75–0.86, vs. r = 0.58, 95% confidence interval 0.46–0.67), while differences between AT compartments were small for the other adipokines. Conclusions: While plasma levels of leptin and FABP4 can be explained in a large and medium part by the amount of AT and SAT gene expression, surprisingly, these predictors explained only little variance for all other investigated adipokines.