Investigating the Impact of Fasting and Refeeding on Blood Biochemical Indicators and Transcriptional Profiles in the Hypothalamus and Subcutaneous Adipose Tissue in Geese.

Fasting and refeeding systems can cause significant short-term fluctuations in nutrient and energy levels, triggering adaptive physiological responses in animals. This study examines the effects of fasting and refeeding on blood biochemical indicators and transcriptional profiles in the hypothalamus and subcutaneous adipose tissue of geese. Biochemical assays reveal that fasting significantly increases levels of free fatty acids and glucagon, while reducing concentrations of triglycerides, leptin, and insulin. Transcriptomic analyses identify a complex transcriptional response in both the hypothalamus and subcutaneous adipose tissue, affecting several metabolic pathways and key genes associated with feed intake and energy metabolism. In subcutaneous adipose tissue, fasting downregulates genes involved in fatty acid synthesis (LPL, SCD, and ACSL1) and upregulates PLIN2, a gene promoting lipid droplet degradation. Fasting affects a variety of metabolic pathways and critical genes in the hypothalamus, including Apelin, insulin, and mTOR signaling pathways. After fasting, the mRNA expression of NOG, GABRD, and IGFBP-1 genes in the hypothalamus are significantly upregulated, while proopiomelanocortin (POMC) gene expression is markedly downregulated. This study highlights the intricate biological responses to nutritional changes in geese, which adds to our understanding of energy balance and metabolic regulation in avian species.

Visceral and subcutaneous adiposity and cardiovascular disease: Unravelling associations and prognostic value.

AIM: The distribution pattern of abdominal adiposity may help determine cardiovascular disease (CVD). Waist circumference (WC) is the most common but imprecise method for measuring abdominal adiposity, as it fails to differentiate between visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (ASAT). This study aimed to determine whether elevated VAT or ASAT provides greater prognostic value for CVD events compared to elevated WC in the general population using data from the UK Biobank. MATERIALS AND METHODS: In this secondary analysis of UK Biobank study, 24 265 participants with available abdominal magnetic resonance imaging data were included. The primary outcome of the study was coronary heart disease (CHD), and secondary outcomes included stroke, heart failure (HF) and atrial fibrillation (AF). Cox regressions for VAT, ASAT and WC were examined in relation to the predefined outcomes on continuous scales using standard deviation (SD) changes and by categories of concordant and discordant values defined by medians. RESULTS: During a mean follow-up period of 12.9 ± 1.8 years, 2641 participants developed CVD events (1296 CHD, 165 stroke, 286 HF and 894 AF) Each 1 SD increase in VAT yielded a hazard ratio (HR) of 1.15 (95% confidence interval [CI]: 1.09-1.22) for CHD risk, whereas ASAT had a HR of 1.10 (95% CI: 1.04-1.18). Further adjustment for WC eliminated the association between ASAT and CHD risk, in contrast to the association between VAT and CHD risk, which remained almost unaffected. Discordant VAT above the median with WC below presented a HR of 1.43 (95% CI: 1.15-1.78) for CHD, compared with concordant VAT and WC below the median. Similar results were found for discordant WC above the median with VAT below, with a HR of 1.46 (95% CI: 1.18-1.81). In contrast, discordant ASAT above the median with WC below was not associated with an increased risk of CHD. Similarly, discordant ASAT above the median with VAT below was not associated with an increased risk of CHD. Additionally, there was no observed association between VAT or ASAT and the risks of stroke, HF or AF after further adjustment for WC. Additionally, there was no observed association between VAT or ASAT and the risks of stroke, HF or AF after further adjustment for WC. CONCLUSION: Incorporating VAT measurements alongside WC data improved the ability to identify individuals at high risk for CHD compared to using WC alone. Both VAT and WC proved to be more accurate indicators of CHD risk than ASAT. However, VAT alone did not fully account for the CHD risk associated with elevated WC levels. Neither VAT nor ASAT showed an association with the risk of stroke, HF and AF.

Exploring the transcriptomic and metabolomic profiles of adipose tissues: Insights and implications for fat grafting.

BACKGROUND: Expanding on previous research on murine fat grafts' metabolic shift, this study delved deeper into the metabolic profiles of human adipose tissues, specifically the superficial subcutaneous adipose tissue (SSAT) and deep subcutaneous adipose tissue (DSAT). METHODS: Utilizing RNA sequencing, metabolomics, and metabolic flux analyses, SSAT and DSAT samples obtained during deep inferior epigastric perforator flap breast reconstructions were examined. Transcript data underwent unsupervised hierarchical clustering and Gene Set Enrichment Analysis. Metabolomics involved analyzing samples for cationic and anionic metabolites via capillary electrophoresis time-of-flight mass spectrometry, followed by principal component analysis (PCA) and heat map generation. Primary adipocytes from SSAT and DSAT were assessed using the Seahorse® extracellular flux analyzer. RESULTS: PCA and heat map analyses highlighted distinct transcriptomic and metabolomic differences between SSAT and DSAT. SSAT predominantly upregulated genes linked to adipogenesis [false discovery rate (FDR) q < 0.0001], oxidative phosphorylation (FDR q < 0.0001), fatty acid metabolism (FDR q < 0.0001), and glycolysis (FDR q = 0.001). In contrast, DSAT showed a significant upregulation in inflammatory response genes (FDR q < 0.05). Metabolite analysis revealed an abundance of glycolytic metabolites in SSAT, whereas DSAT was rich in metabolites associated with fatty acid metabolism and oxidative phosphorylation. Cellular flux analysis further confirmed SSAT's elevated glycolysis and spare oxidative phosphorylation capacities. CONCLUSION: Results highlighted the metabolic uniqueness of SSAT and DSAT in humans, with SSAT exhibiting superior metabolic flexibility. The implications of these metabolic differences, especially in fat grafting procedures, necessitate further research and exploration in future studies.

Effectiveness of first trimester maternal fat tissue measurement in prediction of gestational diabetes: a prospective cohort study.

Objective: The aim was to find a cost-effective, more practical method to be used in the early gestational weeks as an alternative to the oral glucose tolerance test (OGTT) for predicting gestational diabetes mellitus (GDM). The method selected was adipose tissue measurements made in the first trimester. Material and Methods: The study was designed as a prospective, cohort study. Ultrasound images were used to calculate abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) thicknesses of the first trimester pregnant women. Two groups were formed: those who were diagnosed with GDM and those who were not, based on the results of the OGTT performed in the same patients at 24th-28th weeks of gestation. Ultrasonographic records were examined and compared between these two groups using received operator characteristic curves and logistic regression analyses. Results: A total of 292 pregnant women were included, of whom 21.2% were diagnosed with GDM. In the group diagnosed with GDM, SAT, VAT and total adipose tissue (TAT) values were significantly higher than the women who did not have GDM. Threshold values for SAT, VAT and TAT were 18 mm, 55 mm and 55 mm. Conclusion: First trimester SAT, VAT and TAT measurements of pregnant women with GDM were significantly higher than those without GDM diagnosis. Although our results showed that adipose measurements cannot be an alternative to OGTT; they may be a powerful aid in identify at-risk pregnant women, suggesting early OGTT in the first trimester.

MRI-measured periprostatic to subcutaneous adipose tissue thickness ratio as an independent risk factor in prostate cancer patients undergoing radical prostatectomy.

The purpose of this study is to evaluate whether the periprostatic adipose tissue thickness (PPATT) is an independent prognostic factor for prostate cancer patients after laparoscopic radical prostatectomy (LRP). This retrospective cohort study included consecutive prostate cancer patients who underwent LRP treatment at Wuhan Union Hospital from June 2, 2016, to September 7, 2023. PPATT was defined as the thickness of periprostatic fat and was obtained by measuring the shortest vertical distance from the pubic symphysis to the prostate on the midsagittal T2-weighted MR images. Subcutaneous adipose tissue thickness (SATT) was obtained by measuring the shortest vertical distance from the pubic symphysis to the skin at the same slice with PPATT. The primary outcome of the study was biochemical recurrence (BCR), and the secondary outcome was overall survival (OS). Multivariable Cox regression analysis was used to identify independent prognostic factors for prostate cancer survival and prognosis. Based on the optimal cutoff value, 162 patients were divided into a low PPATT/SATT group (n = 82) and a high PPATT/SATT group (n = 80). During the entire follow-up period (median 23.5 months), 26 patients in the high PPATT/SATT group experienced BCR (32.5%), compared to 18 in the low PPATT/SATT group (22.0%). Kaplan-Meier curve analysis indicated that the interval to BCR was significantly shorter in the high PPATT/SATT group (P = 0.037). Multivariable Cox regression analysis revealed that an increase in the PPATT/SATT ratio was associated with BCR (hazard ratio: 1.90, 95% CI, 1.03-3.51; P = 0.040). The PPATT/SATT ratio is a significant independent risk factor for BCR after LRP for prostate cancer patients.

Assessment of body compositions in the prediction of metabolic syndrome in adults.

Background: The musculoskeletal system participates in the pathology of metabolic disorders. Several studies have focused on body composition changes; however, the adipose tissue between muscle bundles with different metabolic statuses has rarely been studied. This study sought to explore the association between body compositions and metabolic disorders in Asians, and identify whether these body compositions can be used to detect metabolic disorders with different waist circumferences (WCs) by computed tomography (CT). Methods: A total of 116 subjects were included in the study and categorized into the following four groups according to WC and metabolic syndrome (MS): (I) the healthy control group; (II) the normal WC with metabolic disorder group; (III) the normal WC with MS group; and (IV) the larger WC with MS group. The International Diabetes Federation (IDF) criteria based on WC, laboratory tests, body mass index (BMI), and medical history was used to diagnose MS. Body composition parameters, such as muscle attenuation, the cross-sectional area of subcutaneous adipose tissue (SAT), muscle, extramyocellular lipid (EMCL), visceral adipose tissue (VAT), and the ratios between different compositions [e.g., the SMR (SAT/muscle), EMR (EMCL/muscle), and VMR (VAT/muscle)] were calculated for the thigh and abdomen. The areas under the curve (AUCs) of the receiver operating characteristic (ROC) curves adjusted for multiple comparisons were used to discriminate among metabolic disorders. Results: The groups with metabolic disorders had more SAT (P=0.001) and EMCL (P=0.040) in the thigh, and more VAT (P=0.001) and a higher SMR (P<0.001) in the abdomen. EMCL and muscle attenuation in the thigh (AUCs =0.790 and 0.791), and the VMR and SMR in the abdomen were better able to diagnose metabolic disorders (AUCs =0.752 and 0.746) than other body composition parameters. While SAT and EMCL in the thigh (AUCs =0.768 and 0.760), and VAT and the VMR in the abdomen (AUCs =0.788 and 0.775) were better able to diagnose MS than other parameters. Conclusions: Body composition parameters for the thigh and abdomen could assist in detecting patients with an increased risk of MS.

A Rare Case of Congenital Generalized Lipodystrophy.

Congenital generalized lipodystrophy type 2 (CGL2) is a rare autosomal recessive disorder characterized by the near-total absence of adipose tissue, leading to various metabolic complications. We present the case of a one-year-old male who exhibited progressive abdominal distension from six months of age. Physical examination revealed distinctive features including triangular facies, hypertelorism, an emaciated appearance with absent buccal fat, and hepatosplenomegaly. Laboratory investigations showed elevated transaminases and a deranged lipid profile, while imaging confirmed hepatosplenomegaly without systemic anomalies. A liver biopsy indicated macrovesicular steatosis and impending cirrhosis. Genetic testing revealed a homozygous pathogenic variant in the BSCL2 gene (c.604C>T), confirming CGL2. The child is under regular follow-up, with genetic counseling provided to the parents. This case underscores the importance of early recognition, genetic diagnosis, and regular monitoring in managing this rare condition.

Effect of abdominal adipose tissue glucose uptake on brain aging.

INTRODUCTION: Abdominal adipose tissue (AT) mass has adverse effects on the brain. This study aimed to investigate the effect of glucose uptake by abdominal AT on brain aging. METHODS: Three-hundred twenty-five participants underwent total-body positron emission tomography scan. Brain age was estimated in an independent test set (n = 98) using a support vector regression model that was built using a training set (n = 227). Effects of abdominal subcutaneous and visceral AT (SAT/VAT) glucose uptake on brain age delta were evaluated using linear regression. RESULTS: Higher VAT glucose uptake was linked to negative brain age delta across all subgroups. Higher SAT glucose uptake was associated with negative brain age delta in lean individuals. In contrast, increased SAT glucose uptake demonstrated positive trends with brain age delta in female and overweight/obese participants. DISCUSSION: Increased glucose uptake of the abdominal VAT has positive influences on the brain, while SAT may not have such influences, except for lean individuals. HIGHLIGHTS: Higher glucose uptake of the visceral adipose tissue was linked to decelerated brain aging. Higher glucose uptake of the subcutaneous adipose tissue (SAT) was associated with negative brain age delta in lean individuals. Faster brain aging was associated with increased glucose uptake of the SAT in female and overweight and obese individuals.

Musculoskeletal glomus tumor: a review of 218 lesions in 176 patients.

OBJECTIVE: To review the spectrum of clinical and imaging features of glomus tumor involving the musculoskeletal system including the typically solitary forms as well as the rarer multifocal forms (glomuvenous malformation and glomangiomatosis). MATERIALS AND METHODS: A retrospective review of our institutional pathology database from 1996 to 2023 identified 176 patients with 218 confirmed glomus tumors. Primary imaging studies included MRI (125), radiographs (100), clinical/intraoperative photos (77), and ultrasound (36). Lesions were divided into two groups: those that are typically solitary involving specific anatomic areas (finger, toe, soft tissue, coccyx, and bone), and those that are multifocal (glomuvenous malformation and glomangiomatosis). RESULTS: The finger was the most frequently involved anatomic location for the classic (sporadic) glomus tumor occurring in 51% of patients, 77% of which were women, with the nail plate involved in more of the 75% of cases. Sporadic lesions involving the skin, subcutaneous adipose tissue, and deep soft tissue were termed "soft tissue," and were identified in 39% of patients, 90% of which were in the extremities and in men in 81% of cases. The multifocal syndromic forms of glomus disease occurred in younger individuals and involved less than 6% of the study group. Patients with glomuvenous malformation presented early with predominantly cutaneous involvement, while those with glomangiomatosis present later, often with both superficial and deep involvement, and a high rate of local tumor recurrence. CONCLUSION: While glomus tumor is generally uncommon, it frequently involves the musculoskeletal extremities. Knowledge of the spectrum of characteristic locations and appearances will facilitate definitive diagnosis.

Convolutional Neural Network-Based Automated Segmentation of Skeletal Muscle and Subcutaneous Adipose Tissue on Thigh MRI in Muscular Dystrophy Patients.

We aim to develop a deep learning-based algorithm for automated segmentation of thigh muscles and subcutaneous adipose tissue (SAT) from T1-weighted muscle MRIs from patients affected by muscular dystrophies (MDs). From March 2019 to February 2022, adult and pediatric patients affected by MDs were enrolled from Azienda Ospedaliera Universitaria Pisana, Pisa, Italy (Institution 1) and the IRCCS Stella Maris Foundation, Calambrone-Pisa, Italy (Institution 2), respectively. All patients underwent a bilateral thighs MRI including an axial T1 weighted in- and out-of-phase (dual-echo). Both muscles and SAT were manually and separately segmented on out-of-phase image sets by a radiologist with 6 years of experience in musculoskeletal imaging. A U-Net1 and U-Net3 were built to automatically segment the SAT, all the thigh muscles together and the three muscular compartments separately. The dataset was randomly split into the on train, validation, and test set. The segmentation performance was assessed through the Dice similarity coefficient (DSC). The final cohort included 23 patients. The estimated DSC for U-Net1 was 96.8%, 95.3%, and 95.6% on train, validation, and test set, respectively, while the estimated accuracy for U-Net3 was 94.1%, 92.9%, and 93.9%. Both of the U-Nets achieved a median DSC of 0.95 for SAT segmentation. The U-Net1 and the U-Net3 achieved an optimal agreement with manual segmentation for the automatic segmentation. The so-developed neural networks have the potential to automatically segment thigh muscles and SAT in patients affected by MDs.

Regional adiposity and insulin sensitivity - interactions with menopause and HIV in middle-aged Black African women.

OBJECTIVE: To explore depot-specific functional aspects of adipose tissue, examining the putative role for menopause and HIV status on insulin sensitivity (SI) and beta-cell function in Black South African women. METHODS: Women (n = 92) from the Middle-Aged Soweto Cohort, including premenopausal HIV-negative (n = 21); premenopausal women living with HIV (WLWH; n = 11); postmenopausal HIV-negative (n = 42); postmenopausal WLWH (n = 18) underwent the following tests: body composition (dual energy x-ray absorptiometry); fasting bloods for sex hormones, inflammation and adipokines; frequently sampled intravenous glucose tolerance test for SI and beta-cell function (disposition index, DI); abdominal (aSAT) and gluteal subcutaneous adipose tissue (gSAT) biopsies for cell size and mRNA expression of adipokines, inflammation, and estrogen receptors [ER]. RESULTS: Depot-specific associations between gene expression and insulin parameters did not differ by HIV or menopause status. Pooled analysis showed significant models for SI (P = 0.002) and DI (P = 0.003). Higher SI was associated with lower leptin and CD11c expression in aSAT and higher adiponectin in gSAT. Higher DI was associated with higher aSAT and gSAT expression of adiponectin, LPL, ERα, and PPARγ, and lower leptin in aSAT. WLWH had higher expression of adiponectin and lower expression of leptin in both aSAT (P = 0.002 and P = 0.005) and gSAT (P = 0.004 and P = 0.002), respectively, and a larger proportion of smaller cells in aSAT (P < 0.001). CONCLUSION: Insulin sensitivity and beta cell function were distinctively associated with aSAT and gSAT. While menopause did not influence these relationships, HIV had a significant effect on adipose tissue, characterised by variations in cell size distribution and transcript levels within the depots.

Relationship between muscle and subcutaneous adipose tissue size and density and proximal femur bone in elderly women with hip fracture.

BACKGROUND: Both osteoporosis and sarcopenia are associated with aging, increasing the likelihood of falls in older adults and consequently raising the risk of hip fractures (HF). AIMS: To explore the relationship between the size and density of muscle and subcutaneous adipose tissue (SAT) and the bone mineral density (BMD) of the proximal femur in elderly women with HF. METHODS: Quantitative computed tomography (QCT) was conducted on the hips of 661 female participants who experienced low-energy acute HFs to measure both areal BMD (aBMD) and volume BMD (vBMD). Measurements were taken for the cross-sectional area (CSA) and density of the muscle around the hip and adjacent SAT. Multivariable linear regression models were applied to assess the relationship between these parameters. RESULTS: Most increases in the density of the gluteus medius and minimus muscle (G.Med/MinM) were correlated with higher BMD in the femoral neck fracture (FNF) group with osteoporosis. In the FNF group, gluteus maximus muscle (G.MaxM) density was negatively associated with the BMD parameters of the proximal femur in individuals with osteoporosis, while they were positively associated with nonosteoporosis. In the intertrochanteric fracture (ITF) group without osteoporosis, both FN aBMD and FN vBMD showed significant correlations with G.Med/MinM density. DISCUSSION: In women with HFs, bone and muscle are closely related. CONCLUSIONS: In older women with HFs, density but not CSA of the G.Med/MinM were associated with BMD parameters of the proximal femur. Osteoporosis may influence the relationship between G.MaxM density and proximal femur BMD in elderly women with FNF.

Transcriptomic Analysis of Newborn Hanwoo Calves: Effects of Maternal Overnutrition during Mid- to Late Pregnancy on Subcutaneous Adipose Tissue and Liver.

This study investigated the transcriptomic responses of subcutaneous adipose tissue (SAT) and liver in newborn Hanwoo calves subjected to maternal overnutrition during mid- to late gestation. Eight Hanwoo cows were randomly assigned to control and treatment groups. The treatment group received a diet of 4.5 kg of concentrate and 6.5 kg of rice straw daily, resulting in intake levels of 8.42 kg DMI, 5.69 kg TDN, and 0.93 kg CP-higher than the control group (6.07 kg DMI, 4.07 kg TDN, and 0.65 kg CP), with respective NEm values of 9.56 Mcal and 6.68 Mcal. Following birth, newly born calves were euthanized humanely as per ethical guidelines, and SAT and liver samples from newborn calves were collected for RNA extraction and analysis. RNA sequencing identified 192 genes that were differentially expressed in the SAT (17 downregulated and 175 upregulated); notably, HSPA6 emerged as the most significantly upregulated gene in the SAT and as the singular upregulated gene in the liver (adj-p value < 0.05). Additionally, differential gene expression analysis highlighted extensive changes across genes associated with adipogenesis, fibrogenesis, and stress response. The functional enrichment pathway and protein-protein interaction (PPI) unraveled the intricate networks and biological processes impacted by overnutrition, including extracellular matrix organization, cell surface receptor signaling, and the PI3K-Akt signaling pathway. These findings underscore maternal overnutrition's substantial influence on developmental pathways, suggesting profound cellular modifications with potential lasting effects on health and productivity. Despite the robust insights that are provided, the study's limitations (sample size) underscore the necessity for further research.

Tumor metabolic activity is associated with subcutaneous adipose tissue radiodensity and survival in non-small cell lung cancer.

BACKGROUND: Cachexia-associated body composition alterations and tumor metabolic activity are both associated with survival of cancer patients. Recently, subcutaneous adipose tissue properties have emerged as particularly prognostic body composition features. We hypothesized that tumors with higher metabolic activity instigate cachexia related peripheral metabolic alterations, and investigated whether tumor metabolic activity is associated with body composition and survival in patients with non-small-cell lung cancer (NSCLC), focusing on subcutaneous adipose tissue. METHODS: A retrospective analysis was performed on a cohort of 173 patients with NSCLC. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scans obtained before treatment were used to analyze tumor metabolic activity (standardized uptake value (SUV) and SUV normalized by lean body mass (SUL)) as well as body composition variables (subcutaneous and visceral adipose tissue radiodensity (SAT/VAT radiodensity) and area; skeletal muscle radiodensity (SM radiodensity) and area). Subjects were divided into groups with high or low SAT radiodensity based on Youden Index of Receiver Operator Characteristics (ROC). Associations between tumor metabolic activity, body composition variables, and survival were analyzed by Mann-Whitney tests, Cox regression, and Kaplan-Meier analysis. RESULTS: The overall prevalence of high SAT radiodensity was 50.9% (88/173). Patients with high SAT radiodensity had shorter survival compared with patients with low SAT radiodensity (mean: 45.3 vs. 50.5 months, p = 0.026). High SAT radiodensity was independently associated with shorter overall survival (multivariate Cox regression HR = 1.061, 95% CI: 1.022-1.101, p = 0.002). SAT radiodensity also correlated with tumor metabolic activity (SULpeak rs = 0.421, p = 0.029; SUVpeak rs = 0.370, p = 0.048). In contrast, the cross-sectional areas of SM, SAT, and VAT were not associated with tumor metabolic activity or survival. CONCLUSION: Higher SAT radiodensity is associated with higher tumor metabolic activity and shorter survival in patients with NSCLC. This may suggest that tumors with higher metabolic activity induce subcutaneous adipose tissue alterations such as decreased lipid density, increased fibrosis, or browning.

The browning and mobilization of subcutaneous white adipose tissue supports efficient skin repair.

Adipocytes in dermis are considered to be important participants in skin repair and regeneration, but the role of subcutaneous white adipose tissue (sWAT) in skin repair is poorly understood. Here, we revealed the dynamic changes of sWAT during wound healing process. Lineage-tracing mouse studies revealed that sWAT would enter into the large wound bed and participate in the formation of granulation tissue. Moreover, sWAT undergoes beiging after skin injury. Inhibition of sWAT beiging by genetically silencing PRDM16, a key regulator to beiging, hindered wound healing process. The transcriptomics results suggested that beige adipocytes in sWAT abundantly express neuregulin 4 (NRG4), which regulated macrophage polarization and the function of myofibroblasts. In diabetic wounds, the beiging of sWAT was significantly suppressed. Thus, adipocytes from sWAT regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes.

Epigenetically active chromatin in neonatal iWAT reveals GABPα as a potential regulator of beige adipogenesis.

Background: Thermogenic beige adipocytes, which dissipate energy as heat, are found in neonates and adults. Recent studies show that neonatal beige adipocytes are highly plastic and contribute to >50% of beige adipocytes in adults. Neonatal beige adipocytes are distinct from recruited beige adipocytes in that they develop independently of temperature and sympathetic innervation through poorly defined mechanisms. Methods: We characterized the neonatal beige adipocytes in the inguinal white adipose tissue (iWAT) of C57BL6 postnatal day 3 and 20 mice (P3 and P20) by imaging, genome-wide RNA-seq analysis, ChIP-seq analysis, qRT-PCR validation, and biochemical assays. Results: We found an increase in acetylated histone 3 lysine 27 (H3K27ac) on the promoter and enhancer regions of beige-specific gene UCP1 in iWAT of P20 mice. Furthermore, H3K27ac ChIP-seq analysis in the iWAT of P3 and P20 mice revealed strong H3K27ac signals at beige adipocyte-associated genes in the iWAT of P20 mice. The integration of H3K27ac ChIP-seq and RNA-seq analysis in the iWAT of P20 mice reveal epigenetically active signatures of beige adipocytes, including oxidative phosphorylation and mitochondrial metabolism. We identify the enrichment of GA-binding protein alpha (GABPα) binding regions in the epigenetically active chromatin regions of the P20 iWAT, particularly on beige genes, and demonstrate that GABPα is required for beige adipocyte differentiation. Moreover, transcriptomic analysis and glucose oxidation assays revealed increased glycolytic activity in the neonatal iWAT from P20. Conclusions: Our findings demonstrate that epigenetic mechanisms regulate the development of peri-weaning beige adipocytes via GABPα. Further studies to better understand the upstream mechanisms that regulate epigenetic activation of GABPα and characterization of the metabolic identity of neonatal beige adipocytes will help us harness their therapeutic potential in metabolic diseases.

Adipose Tissue Segmentation after Lung Slice Localization in Chest CT Images Based on ConvBiGRU and Multi-Module UNet.

The distribution of adipose tissue in the lungs is intricately linked to a variety of lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Accurate detection and quantitative analysis of subcutaneous and visceral adipose tissue surrounding the lungs are essential for effectively diagnosing and managing these diseases. However, there remains a noticeable scarcity of studies focusing on adipose tissue within the lungs on a global scale. Thus, this paper introduces a ConvBiGRU model for localizing lung slices and a multi-module UNet-based model for segmenting subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), contributing to the analysis of lung adipose tissue and the auxiliary diagnosis of lung diseases. In this study, we propose a bidirectional gated recurrent unit (BiGRU) structure for precise lung slice localization and a modified multi-module UNet model for accurate SAT and VAT segmentations, incorporating an additive weight penalty term for model refinement. For segmentation, we integrate attention, competition, and multi-resolution mechanisms within the UNet architecture to optimize performance and conduct a comparative analysis of its impact on SAT and VAT. The proposed model achieves satisfactory results across multiple performance metrics, including the Dice Score (92.0% for SAT and 82.7% for VAT), F1 Score (82.2% for SAT and 78.8% for VAT), Precision (96.7% for SAT and 78.9% for VAT), and Recall (75.8% for SAT and 79.1% for VAT). Overall, the proposed localization and segmentation framework exhibits high accuracy and reliability, validating its potential application in computer-aided diagnosis (CAD) for medical tasks in this domain.

A new method that facilitates the diagnosis of endometrial cancer: the ratio of endometrial thickness to the full thickness of the uterine wall and subcutaneous adipose tissue measurements.

Introduction: The aim of the present study was to investigate the association between some risk factors and endometrial pathologies determined by transvaginal sonography (TVS), as well as the diagnostic predictive values of serum oestradiol (E2) levels, subcutaneous adipose tissue (SAT) thickness, endometrium thickness (ET), and the ratio of ET to uterine wall full thickness (UWT) in differential diagnosis of malignant, precancerous, and benign pathologies of endometrium in patients with postmenopausal bleeding (PMB) or with asymptomatic increased endometrial thickness. Material and methods: The study was conducted with 211 women who applied to the hospital with complaints of PMB or ET of 5 mm or more in their routine controls. Venous blood samples were taken for complete blood count and the measurement of E2 levels. Patients also underwent TVS; ET, UWT, and the ratio of ET to UWT were measured. Results: Menopausal age and body mass index averages were significantly higher in atypical hyperplasia and endometrial cancer (EC) groups. Endometrial thickness and endometrial thickness/uterine wall full thickness ratio measured by TVS were significantly higher in all precancerous pathologies and EC. Subcutaneous adipose tissue thickness was significantly higher in all precancerous pathologies and EC. Oestradiol levels were higher in the atypical hyperplasia and EC groups. Conclusions: Postmenopausal bleeding is a common symptom of EC, but in some cases this disease may occur asymptomatically. Measurement of the endometrium thickness, and the ratio of endometrium thickness/uterine wall full thickness and SAT thickness by sonography has a high predictive value for this disease.

Influence of glucagon-like peptide-1 receptor agonists on fat accumulation in patients with diabetes mellitus and non-alcoholic fatty liver disease or obesity: A systematic review and meta-analysis of randomized control trials.

AIM: This systematic review and meta-analysis aimed to comprehensively evaluate the impact of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in individuals with diabetes mellitus and non-alcoholic fatty liver disease (NAFLD) or obesity. METHODS: A search of PubMed, Embase, and Web of Science until October 2023 identified 13 Randomized Controlled Trials (RCTs) meeting the inclusion criteria. Bias risk was assessed using the Cochrane risk-of-bias instrument. Statistical analysis utilized standard mean differences (SMD) in Review Manager 5.4. Heterogeneity and publication bias were assessed. This study used the protocol registered with the Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY2023110020). RESULTS: GLP-1RA treatment significantly reduced VAT (SMD -0.55, 95 % CI [-0.90, -0.19]), SAT (SMD -0.59, 95 % CI [-0.99, -0.19]), body weight (SMD -1.07, 95 % CI [-1.67, -0.47]), and body mass index (BMI) (SMD -1.10, 95 % CI [-1.74, -0.47]) compared to controls. Heterogeneity was observed for VAT (I2 = 79 %, P < 0.01), SAT (I2 = 73 %, P < 0.01), body weight (I2 = 82 %, P < 0.01), and BMI (I2 = 82 %, P < 0.01). No publication bias was detected for VAT (P = 0.57) and SAT (P = 0.18). GLP-1RA treatment improved fasting blood glucose (FBG), postprandial glucose (PPG), hemoglobin A1c (HbA1c), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and fibrosis-4 (FIB-4). CONCLUSIONS: This meta-analysis highlights GLP-1RAs' potential to reduce fat accumulation, body weight, and BMI and improve glycemic control in individuals with diabetes mellitus and NAFLD or obesity. These findings supported using GLP-1RAs as promising therapeutic agents to address abnormal adipose tissue distribution and metabolic dysfunction.

Creatinine-to-cystatin C ratio and body composition predict response to PD-1 inhibitors-based combination treatment in metastatic gastric cancer.

Background: Creatinine-to-cystatin C ratio (CCR) and body composition (BC) parameters have emerged as significant prognostic factors in cancer patients. However, the potential effects of CCR in gastric cancer (GC) remains to be elucidated. This multi-center retrospective study explored the predictive and prognostic value of CCR and BC-parameters in patients with metastatic GC receiving PD-1 inhibitors-based combination therapy. Methods: One hundred and thirteen GC patients undergoing PD-1 inhibitors-based combination therapy were enrolled at three academic medical centers from January 2021 to July 2023. A deep-learning platform based on U-Net was developed to automatically segment skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI) and visceral adipose tissue index (VATI). Patients were divided into two groups based on the median of CCR or the upper tertile of BC-parameters. Logistic and Cox regression analysis were used to determine the effect of CCR and BC-parameters in predicting response rates and survival rates. Results: The CCR was positively correlated with SMI (r=0.43; P<0.001), but not with SATI or VATI (P>0.05). Multivariable logistic analysis identified that both low CCR (OR=0.423, P=0.066 for ORR; OR=0.026, P=0.005 for DCR) and low SATI (OR=0.270, P=0.020 for ORR; OR=0.149, P=0.056 for DCR) were independently associated with worse objective response rate (ORR) and disease control rate (DCR). Patients with low CCR or low SATI had significantly lower 8-month progression-free survival (PFS) rate and 16-month overall survival (OS) rate than those with high CCR (PFS rate, 37.6% vs. 55.1%, P=0.011; OS rate, 19.4% vs. 44.9%, P=0.002) or those with high SATI (PFS rate, 37.2% vs. 53.8%, P=0.035; OS rate, 8.0% vs. 36.0%, P<0.001). Multivariate Cox analysis showed that low CCR (HR=2.395, 95% CI: 1.234-4.648, P=0.010 for PFS rate; HR=2.528, 95% CI: 1.317-4.854, P=0.005 for OS rate) and low SATI (HR=2.188, 95% CI: 1.050-4.560, P=0.037 for PFS rate; HR=2.818, 95% CI: 1.381-5.752, P=0.004 for OS rate) were both independent prognostic factors of poor 8-month PFS rate and 16-month OS rate. A nomogram based on CCR and BC-parameters showed a good performance in predicting the 12- and 16-month OS, with a concordance index of 0.756 (95% CI, 0.722-0.789). Conclusions: Low pre-treatment CCR and SATI were independently associated with lower response rates and worse survival in patients with metastatic GC receiving PD-1 inhibitors-based combination therapy.