Tumoral periprostatic adipose tissue exovesicles-derived miR-20a-5p regulates prostate cancer cell proliferation and inflammation through the RORA gene.

BACKGROUND: From the first steps of prostate cancer (PCa) initiation, tumours are in contact with the most-proximal adipose tissue called periprostatic adipose tissue (PPAT). Extracellular vesicles are important carriers of non-coding RNA such as miRNAs that are crucial for cellular communication. The secretion of extracellular vesicles by PPAT may play a key role in the interactions between adipocytes and tumour. Analysing the PPAT exovesicles (EVs) derived-miRNA content can be of great relevance for understanding tumour progression and aggressiveness. METHODS: A total of 24 samples of human PPAT and 17 samples of perivesical adipose tissue (PVAT) were used. EVs were characterized by western blot and transmission electron microscopy (TEM), and uptake by PCa cells was verified by confocal microscopy. PPAT and PVAT explants were cultured overnight, EVs were isolated, and miRNA content expression profile was analysed. Pathway and functional enrichment analyses were performed seeking potential miRNA targets. In vitro functional studies were evaluated using PCa cells lines, miRNA inhibitors and target gene silencers. RESULTS: Western blot and TEM revealed the characteristics of EVs derived from PPAT (PPAT-EVs) samples. The EVs were up taken and found in the cytoplasm of PCa cells. Nine miRNAs were differentially expressed between PPAT and PVAT samples. The RORA gene (RAR Related Orphan Receptor A) was identified as a common target of 9 miRNA-regulated pathways. In vitro functional analysis revealed that the RORA gene was regulated by PPAT-EVs-derived miRNAs and was found to be implicated in cell proliferation and inflammation. CONCLUSION: Tumour periprostatic adipose tissue is linked to PCa tumour aggressiveness and could be envisaged for new therapeutic strategies.

Fatty infiltration and ventricular premature beats originating from right ventricular outflow tract: association or causality?

BACKGROUND: Anatomical evidence reveals heterogeneous fat distribution in both atrial and ventricular myocardium that are considered normal, but at the same time arrhythmogenic, and numerous cardiac pathophysiological conditions are associated with myocardial fat deposits. The relationship between fatty infiltration, especially in the epicardial layer and its pathophysiological implication is not completely understood. AIM: The aim of this study was to establish a positive or negative relationship between the ventricular burden and several parameters related to right ventricle (RV) adipose tissue - the RV thickness, RV indexed mass, body mass index (BMI), age, gender. PATIENTS, MATERIALS AND METHODS: Twenty-three patients with documented premature ventricular contractions (PVCs) originating from right ventricular outflow tract based on electrocardiography (ECG) evaluation were hospitalized between January 2018-November 2022 for electrophysiological study and PVCs ablation. Data obtained after collecting the clinical characteristics, ECG, RV measurements from transthoracic echocardiography (TTE), cardiac computed tomography (CT) and magnetic resonance imaging (MRI) were analyzed. RESULTS: A weak positive relationship between the ventricular burden and BMI (r=0.14, p=0.49), tricuspid annular plane systolic excursion (TAPSE) (r=0.07, p=0.7), the RV thickness (r=0.03, p=0.8), epicardial adipose tissue (r=0.13, p=0.55), RV mass indexed (r=0.05, p=0.82) was observed. No clear cut-off of the PVCs burden could be established in terms related to the increase in BMI, RV thickness, epicardial adipose tissue, RV mass indexed. CONCLUSIONS: No significant positive or negative relationship between the ventricular burden and the RV thickness, RV indexed mass were found in individuals with a high PVCs originating from right ventricular outflow tract (RVOT) burden.

Association of MRI findings with paraspinal muscles fat infiltration at lower lumbar levels in patients with chronic low back pain: a multicenter prospective study.

OBJECTIVE: In chronic low back pain (CLBP), the relationship between spinal pathologies and paraspinal muscles fat infiltration remains unclear. This study aims to evaluate the relationship between MRI findings and paraspinal muscles morphology and fat infiltration in CLBP patients by quantitative MRI. METHODS: All the CLBP patients were enrolled from July 2021 to December 2022 in four medical institutions. The cross-sectional area (CSA) and proton density fat fraction (PDFF) of the multifidus (MF) and erector spinae (ES) muscles at the central level of the L4/5 and L5/S1 intervertebral discs were measured. MRI findings included degenerative lumbar spondylolisthesis (DLS), intervertebral disc degeneration (IVDD), facet arthrosis, disc bulge or herniation, and disease duration. The relationship between MRI findings and the paraspinal muscles PDFF and CSA in CLBP patients was analyzed. RESULTS: A total of 493 CLBP patients were included in the study (198 females, 295 males), with an average age of 45.68 ± 12.91 years. Our research indicates that the number of MRI findings are correlated with the paraspinal muscles PDFF at the L4/5 level, but is not significant. Moreover, the grading of IVDD is the primary factor influencing the paraspinal muscles PDFF at the L4-S1 level (BES at L4/5=1.845, P < 0.05); DLS was a significant factor affecting the PDFF of MF at the L4/5 level (B = 4.774, P < 0.05). After including age, gender, and Body Mass Index (BMI) as control variables in the multivariable regression analysis, age has a significant positive impact on the paraspinal muscles PDFF at the L4-S1 level, with the largest AUC for ES PDFF at the L4/5 level (AUC = 0.646, cut-off value = 47.5), while males have lower PDFF compared to females. BMI has a positive impact on the ES PDFF only at the L4/5 level (AUC = 0.559, cut-off value = 24.535). CONCLUSION: The degree of paraspinal muscles fat infiltration in CLBP patients is related to the cumulative or synergistic effects of multiple factors, especially at the L4/L5 level. Although age and BMI are important factors affecting the degree of paraspinal muscles PDFF in CLBP patients, their diagnostic efficacy is moderate.

Breast volume in non-obese females is related to breast adipose cell hypertrophy, inflammation, and COX2 expression.

BACKGROUND: Breast hypertrophy seems to be a risk factor for breast cancer and the amount and characteristics of breast adipose tissue may play important roles. The main aim of this study was to investigate associations between breast volume in normal weight women and hypertrophic adipose tissue and inflammation. METHODS: Fifteen non-obese women undergoing breast reduction surgery were examined. Breast volume was measured with plastic cups and surgery was indicated if the breast was 800 ml or larger according to Swedish guidelines. We isolated adipose cells from the breasts and ambient subcutaneous tissue to measure cell size, cell inflammation and other known markers of risk of developing breast cancer including COX2 gene activation and MAPK, a cell proliferation regulator. RESULTS: Breast adipose cell size was characterized by cell hypertrophy and closely related to breast volume. The breast adipose cells were also characterized by being pro-inflammatory with increased IL-6, IL-8, IL-1ß, CCL-2, TNF-a and an increased marker of cell senescence GLB1/ß-galactosidase, commonly increased in hypertrophic adipose tissue. The prostaglandin synthetic marker COX2 was also increased in the hypertrophic cells and COX2 has previously been shown to be an important marker of risk of developing breast cancer. Interestingly, the phosphorylation of the proliferation marker MAPK was also increased in the hypertrophic adipose cells. CONCLUSION: Taken together, these findings show that increased breast volume in non-obese women is associated with adipose cell hypertrophy and dysfunction and characterized by increased inflammation and other markers of increased risk for developing breast cancer. TRIAL REGISTRATION: Projektdatabasen FoU i VGR, project number: 249191 (https://www.researchweb.org/is/vgr/project/249191).

Usefulness of Body Fat and Visceral Fat Determined by Bioimpedanciometry versus Body Mass Index and Waist Circumference in Predicting Elevated Values of Different Risk Scales for Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Obesity constitutes a public health problem worldwide and causes non-alcoholic fatty liver disease (MALFD), the leading cause of liver disease in developed countries, which progresses to liver cirrhosis and liver cancer. MAFLD is associated with obesity and can be evaluated by validated formulas to assess MAFLD risk using different parameters such as the body mass index (BMI) and waist circumference (WC). However, these parameters do not accurately measure body fat. As MAFLD is strongly associated with obesity, we hypothesize that measuring body and visceral fat by electrical bioimpedance is an efficient method to predict the risk of MAFLD. The objective of our work was to demonstrate that electrical bioimpedance is a more efficient method than the BMI or WC to predict an elevated risk of MAFLD. METHODS: A cross-sectional, descriptive study involving 8590 Spanish workers in the Balearic Islands was carried out. The study's sample of employees was drawn from those who underwent occupational medicine examinations between January 2019 and December 2020. Five MAFLD risk scales were determined for evaluating very high levels of body fat and visceral fat. The determination of body and visceral fat was performed using bioimpedanciometry. Student's t-test was employed to ascertain the mean and standard deviation of quantitative data. The chi-square test was used to find prevalences for qualitative variables, while ROC curves were used to define the cut-off points for body and visceral fat. The calculations included the area under the curve (AUC), the cut-off points along with their Youden index, sensitivity, and specificity. Correlation and concordance between the various scales were determined using Pearson's correlation index and Cohen's kappa, respectively. RESULTS: As both total body fat and visceral fat increase, the risk of MAFLD increases with a statistically significant result (p < 0.001), presenting a higher risk in men. The areas under the curve (AUC) of the five scales that assess overweight and obesity to determine the occurrence of high values of the different MAFLD risk scales were very high, most of them exceeding 0.9. These AUC values were higher for visceral and body fat than for the BMI or waist circumference. FLD-high presented the best results in men and women with the AUC at around 0.97, both for visceral fat and total body fat, with a high Youden index in all cases (women body fat = 0.830, visceral fat = 0.892; men body fat = 0.780, visceral fat = 0.881). CONCLUSIONS: In our study, all the overweight and obesity scales show a very good association with the scales assessing the risk of MAFLD. These values are higher for visceral and body fat than for waist circumference and the BMI. Both visceral fat and body fat are better associated than the BMI and waist circumference with MAFLD risk scales.

Postmenopausal giant uterine adenomyoma with adipose metaplasia: A case report and literature review.

RATIONALE: Uterine adenomyomas (UAs) are common benign tumors, usually not exceeding 280 g or the weight of the uterus at 12 weeks gestation. Postmenopausal giant UAs of diameter larger than 20 cm are rare, as well as steatosis, but curable by surgical excision. Few cases of postmenopausal giant UAs have been reported. PATIENT CONCERNS: Herein, we report a case of a 70-year-old female patient who presented with a giant pelvic tumor of about 20 cm × 18 cm × 20 cm with postmenopausal vaginal bleeding, and whose radiographic manifestations did not exclude the possibility of uterine malignancy. DIAGNOSES: Histopathology confirms an adenomyoma with partial adipose metaplasia. INTERVENTIONS: We did an open laparotomy of hysterectomy, bi-adnexectomy, and pelvic adhesion release for the patient. OUTCOMES: Pathology revealed adenomyoma with adipose metaplasia. The patient recovered well and was discharged on postoperative day 7 with satisfactory follow-up.

Fatty infiltration in the musculoskeletal system: pathological mechanisms and clinical implications.

Fatty infiltration denotes the anomalous accrual of adipocytes in non-adipose tissue, thereby generating toxic substances with the capacity to impede the ordinary physiological functions of various organs. With aging, the musculoskeletal system undergoes pronounced degenerative alterations, prompting heightened scrutiny regarding the contributory role of fatty infiltration in its pathophysiology. Several studies have demonstrated that fatty infiltration affects the normal metabolism of the musculoskeletal system, leading to substantial tissue damage. Nevertheless, a definitive and universally accepted generalization concerning the comprehensive effects of fatty infiltration on the musculoskeletal system remains elusive. As a result, this review summarizes the characteristics of different types of adipose tissue, the pathological mechanisms associated with fatty infiltration in bone, muscle, and the entirety of the musculoskeletal system, examines relevant clinical diseases, and explores potential therapeutic modalities. This review is intended to give researchers a better understanding of fatty infiltration and to contribute new ideas to the prevention and treatment of clinical musculoskeletal diseases.

Increased secretion of adipocyte-derived extracellular vesicles is associated with adipose tissue inflammation and the mobilization of excess lipid in human obesity.

BACKGROUND: Obesity is a worldwide epidemic characterized by adipose tissue (AT) inflammation. AT is also a source of extracellular vesicles (EVs) that have recently been implicated in disorders related to metabolic syndrome. However, our understanding of mechanistic aspect of obesity's impact on EV secretion from human AT remains limited. METHODS: We investigated EVs from human Simpson Golabi Behmel Syndrome (SGBS) adipocytes, and from AT as well as plasma of subjects undergoing bariatric surgery. SGBS cells were treated with TNFα, palmitic acid, and eicosapentaenoic acid. Various analyses, including nanoparticle tracking analysis, electron microscopy, high-resolution confocal microscopy, and gas chromatography-mass spectrometry, were utilized to study EVs. Plasma EVs were analyzed with imaging flow cytometry. RESULTS: EVs from mature SGBS cells differed significantly in size and quantity compared to preadipocytes, disagreeing with previous findings in mouse adipocytes and indicating that adipogenesis promotes EV secretion in human adipocytes. Inflammatory stimuli also induced EV secretion, and altered EV fatty acid (FA) profiles more than those of cells, suggesting the role of EVs as rapid responders to metabolic shifts. Visceral AT (VAT) exhibited higher EV secretion compared to subcutaneous AT (SAT), with VAT EV counts positively correlating with plasma triacylglycerol (TAG) levels. Notably, the plasma EVs of subjects with obesity contained a higher number of adiponectin-positive EVs than those of lean subjects, further demonstrating higher AT EV secretion in obesity. Moreover, plasma EV counts of people with obesity positively correlated with body mass index and TNF expression in SAT, connecting increased EV secretion with AT expansion and inflammation. Finally, EVs from SGBS adipocytes and AT contained TAGs, and EV secretion increased despite signs of less active lipolytic pathways, indicating that AT EVs could be involved in the mobilization of excess lipids into circulation. CONCLUSIONS: We are the first to provide detailed FA profiles of human AT EVs. We report that AT EV secretion increases in human obesity, implicating their role in TAG transport and association with adverse metabolic parameters, thereby emphasizing their role in metabolic disorders. These findings promote our understanding of the roles that EVs play in human AT biology and metabolic disorders.

Vertebral bone quality score was associated with paraspinal muscles fat infiltration, but not modic classification in patients with chronic low back pain: a prospective cross-sectional study.

BACKGROUND: The lumbar vertebra and paraspinal muscles play an important role in maintaining the stability of the lumbar spine. Therefore, the aim of this study was to investigate the relationship between paraspinal muscles fat infiltration and vertebral body related changes [vertebral bone quality (VBQ) score and Modic changes (MCs)] in patients with chronic low back pain (CLBP). METHODS: Patients with CLBP were prospectively collected in four hospitals and all patients underwent 3.0T magnetic resonance scanning. Basic clinical information was collected, including age, sex, course of disease (COD), and body mass index (BMI). MCs were divided into 3 types based on their signal intensity on T1 and T2-weighted imaging. VBQ was obtained by midsagittal T1-weighted imaging (T1WI) and calculated using the formula: SIL1-4/SICSF. The Proton density fat fraction (PDFF) values and cross-sectional area (CSA) of paraspinal muscles were measured on the fat fraction map from the iterative decomposition of water and fat with the echo asymmetry and least-squares estimation quantitation (IDEAL-IQ) sequences and in/out phase images at the central level of the L4/5 and L5/S1 discs. RESULTS: This study included 476 patients with CLBP, including 189 males and 287 females. 69% had no Modic changes and 31% had Modic changes. There was no difference in CSA and PDFF for multifidus(MF) and erector spinae (ES) at both levels between Modic type I and type II, all P values>0.05. Spearman correlation analysis showed that VBQ was weakly negatively correlated with paraspinal muscles CSA (all r values < 0.3 and all p values < 0.05), moderately positive correlation with PDFF of MF at L4/5 level (r values = 0.304, p values<0.001) and weakly positively correlated with PDFF of other muscles (all r values<0.3 and all p values<0.001). Multivariate linear regression analysis showed that age (ß = 0.141, p < 0.001), gender (ß = 4.285, p < 0.001) and VBQ (ß = 1.310, p = 0.001) were related to the total PDFF of muscles. For MCs, binary logistic regression showed that the odds ratio values of age, BMI and COD were 1.092, 1.082 and 1.004, respectively (all p values ＜ 0.05). CONCLUSIONS: PDFF of paraspinal muscles was not associated with Modic classification. In addition to age and gender, PDFF of paraspinal muscles is also affected by VBQ. Age and BMI are considered risk factors for the MCs in CLBP patients.

Advances in the interaction between lumbar intervertebral disc degeneration and fat infiltration of paraspinal muscles: critical summarization, classification, and perspectives.

More than 619 million people in the world suffer from low back pain (LBP). As two potential inducers of LBP, intervertebral disc degeneration (IVDD) and fat infiltration of paraspinal muscles (PSMs) have attracted extensive attention in recent years. So far, only one review has been presented to summarize their relationship and relevant mechanisms. Nevertheless, it has several noticeable drawbacks, such as incomplete categorization and discussion, lack of practical proposals, etc. Consequently, this paper aims to systematically summarize and classify the interaction between IVDD and fat infiltration of PSMs, thus providing a one-stop search handbook for future studies. As a result, four mechanisms of IVDD leading to fat infiltration of PSMs and three mechanisms of fat infiltration in PSMs causing IVDD are thoroughly analyzed and summarized. The typical reseaches are tabulated and evaluated from four aspects, i.e., methods, conclusions, benefits, and drawbacks. We find that IVDD and fat infiltration of PSMs is a vicious cycle that can promote the occurrence and development of each other, ultimately leading to LBP and disability. Finally, eight perspectives are proposed for future in-depth research.

Carbohydrate antigen 125 on epicardial fat and its association with local inflammation and fibrosis-related markers.

BACKGROUND: Carbohydrate antigen 125 (CA125) is a proteolytic fragment of MUC-16 that is increased in heart failure (HF) and associated with inflammation, fluid overload, and worse adverse events. Our main objective was to study the expression of CA125 on epicardium and its association with inflammation, adipogenesis, and fibrosis. METHODS: Epicardial fat biopsies and blood were obtained from 151 non-selected patients undergoing open heart surgery. Immunohistochemistry, ELISA, or real-time PCR were used for analyzing protein or mRNA expression levels of CA125 and markers of inflammatory cells, fibroblasts, and adipocytes. Epithelial or stromal cells from epicardium were isolated and cultured to identify CA125 and its association with the adipogenesis and fibrosis pathways, respectively. RESULTS: The median age was 71 (63-74) years, 106 patients (70%) were male, and 62 (41%) had an established diagnosis of HF before surgery. The slice of epicardial fat biopsy determined a positive and colorimetric staining on the epithelial layer after incubating with the CA125 M11 antibody, providing the first description of CA125 expression in the human epicardium. Epicardial CA125 showed a strong and positive correlation with markers of inflammation and fibrosis in the epicardial fat tissue while exhibiting a negative correlation with markers of the adipogenesis pathway. This relationship remained significant after adjusting for potential confounders such as a prior HF diagnosis and plasma CA125 levels. CONCLUSION: Epicardial cells express CA125, which is positively associated with inflammatory and fibroblast markers in epicardial adipose tissue. These results suggest that CA125 may be biologically involved in HF progression (transition from adipogenesis to fibrosis).

M6A modification and T cells in adipose tissue inflammation.

Adipose tissue in the obese state can lead to low-grade chronic inflammation while inducing or exacerbating obesity-related metabolic diseases and impairing overall health.T cells, which are essential immune cells similar to macrophages, are widely distributed in adipose tissue and perform their immunomodulatory function; they also cross-talk with other cells in the vascular stromal fraction. Based on a large number of studies, it has been found that N6 methyl adenine (m6A) is one of the most representative of epigenetic modifications, which affects the crosstalk between T cells, as well as other immune cells, in several ways and plays an important role in the development of adipose tissue inflammation and related metabolic diseases. In this review, we first provide an overview of the widespread presence of T cells in adipose tissue and summarize the key role of T cells in adipose tissue inflammation. Next, we explored the effects of m6A modifications on T cells in adipose tissue from the perspective of adipose tissue inflammation. Finally, we discuss the impact of m6a-regulated crosstalk between T cells and immune cells on the prospects for improving adipose tissue inflammation research, providing additional new ideas for the treatment of obesity.

Excessive accumulation of epicardial adipose tissue promotes microvascular obstruction formation after myocardial ischemia/reperfusion through modulating macrophages polarization.

BACKGROUND: Owing to its unique location and multifaceted metabolic functions, epicardial adipose tissue (EAT) is gradually emerging as a new metabolic target for coronary artery disease risk stratification. Microvascular obstruction (MVO) has been recognized as an independent risk factor for unfavorable prognosis in acute myocardial infarction patients. However, the concrete role of EAT in the pathogenesis of MVO formation in individuals with ST-segment elevation myocardial infarction (STEMI) remains unclear. The objective of the study is to evaluate the correlation between EAT accumulation and MVO formation measured by cardiac magnetic resonance (CMR) in STEMI patients and clarify the underlying mechanisms involved in this relationship. METHODS: Firstly, we utilized CMR technique to explore the association of EAT distribution and quantity with MVO formation in patients with STEMI. Then we utilized a mouse model with EAT depletion to explore how EAT affected MVO formation under the circumstances of myocardial ischemia/reperfusion (I/R) injury. We further investigated the immunomodulatory effect of EAT on macrophages through co-culture experiments. Finally, we searched for new therapeutic strategies targeting EAT to prevent MVO formation. RESULTS: The increase of left atrioventricular EAT mass index was independently associated with MVO formation. We also found that increased circulating levels of DPP4 and high DPP4 activity seemed to be associated with EAT increase. EAT accumulation acted as a pro-inflammatory mediator boosting the transition of macrophages towards inflammatory phenotype in myocardial I/R injury through secreting inflammatory EVs. Furthermore, our study declared the potential therapeutic effects of GLP-1 receptor agonist and GLP-1/GLP-2 receptor dual agonist for MVO prevention were at least partially ascribed to its impact on EAT modulation. CONCLUSIONS: Our work for the first time demonstrated that excessive accumulation of EAT promoted MVO formation by promoting the polarization state of cardiac macrophages towards an inflammatory phenotype. Furthermore, this study identified a very promising therapeutic strategy, GLP-1/GLP-2 receptor dual agonist, targeting EAT for MVO prevention following myocardial I/R injury.

Novel perspectives on autophagy-oxidative stress-inflammation axis in the orchestration of adipogenesis.

Adipose tissue, an indispensable organ, fulfils the pivotal role of energy storage and metabolism and is instrumental in maintaining the dynamic equilibrium of energy and health of the organism. Adipocyte hypertrophy and adipocyte hyperplasia (adipogenesis) are the two primary mechanisms of fat deposition. Mature adipocytes are obtained by differentiating mesenchymal stem cells into preadipocytes and redifferentiation. However, the mechanisms orchestrating adipogenesis remain unclear. Autophagy, an alternative cell death pathway that sustains intracellular energy homeostasis through the degradation of cellular components, is implicated in regulating adipogenesis. Furthermore, adipose tissue functions as an endocrine organ, producing various cytokines, and certain inflammatory factors, in turn, modulate autophagy and adipogenesis. Additionally, autophagy influences intracellular redox homeostasis by regulating reactive oxygen species, which play pivotal roles in adipogenesis. There is a growing interest in exploring the involvement of autophagy, inflammation, and oxidative stress in adipogenesis. The present manuscript reviews the impact of autophagy, oxidative stress, and inflammation on the regulation of adipogenesis and, for the first time, discusses their interactions during adipogenesis. An integrated analysis of the role of autophagy, inflammation and oxidative stress will contribute to elucidating the mechanisms of adipogenesis and expediting the exploration of molecular targets for treating obesity-related metabolic disorders.

Long-Term pemafibrate treatment exhibits limited impact on body fat mass in patients with hypertriglyceridemia accompanying NAFLD.

Aim: Short-term use of pemafibrate (PEM), a selective modulator of peroxisome proliferator-activated receptor alpha, has been reported to improve abnormal liver function in patients with nonalcoholic fatty liver disease with hypertriglyceridemia (HTG-NAFLD). This study aimed to clarify the effects and predictive factors of long-term 72-week PEM administration on body composition, and laboratory tests in HTG-NAFLD patients. Methods: Fifty-three HTG-NAFLD patients receiving a 72-week PEM regimen were retrospectively enrolled. Routine blood and body composition results were analyzed immediately before and at the end of the study period. Results: PEM treatment significantly improved liver enzyme levels such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and gamma-glutamyl transferase, along with lipid profiles including triglyceride, total cholesterol, and low-density lipoprotein cholesterol. PEM did not have any detectable impact on body composition parameters. The factors of female, higher AST (≥ 46 U/L) and fat mass (≥ 31.9%), as well as lower soft lean mass (< 61.6%), skeletal muscle mass (< 36%), and skeletal muscle mass index (< 6.9 kg/m2) were significantly associated with the treatment response status of a > 30% decrease in ALT. All patients completed the treatment without any adverse effects. Conclusions: Long-term PEM treatment had a positive impact on liver enzymes and lipid profiles, but it did not result in significant changes in body composition among HTG-NAFLD patients. In predicting the response to PEM treatment, the evaluation of AST and body composition may be useful.

Preliminary Single-Cell RNA-Sequencing Analysis Uncovers Adipocyte Heterogeneity in Lipedema.

Background: Despite its increasing incidence and prevalence throughout Western countries, lipedema continues to be a very enigmatic disease, often misunderstood or misdiagnosed by the medical community and with an intrinsic pathology that is difficult to trace. The nature of lipedemic tissue is one of hypertrophic adipocytes and poor tissue turnover. So far, there are no identified pathways responsible, and little is known about the cell populations of lipedemic fat. Methods: Adipose tissue samples were collected from affected areas of both lipedema and healthy participants. For single-cell RNA sequencing analysis, the samples were dissociated into single-cell suspensions using enzymatic digestion and then encapsulated into nanoliter-sized droplets containing barcoded beads. Within each droplet, cellular mRNA was converted into complementary DNA. Complementary DNA molecules were then amplified for downstream analysis. Results: The single-cell RNA-sequencing analysis revealed three distinct adipocyte populations at play in lipedema. These populations have unique gene signatures which can be characterized as a lipid generating adipocyte, a disease catalyst adipocyte, and a lipedemic adipocyte. Conclusions: The single-cell RNA sequencing of lipedemic tissue samples highlights a triad of distinct adipocyte subpopulations, each characterized by unique gene signatures and functional roles. The interplay between these adipocyte subtypes offers promising insights into the complex pathophysiology of lipedema.

Perinephric fat stranding is associated with increased age and stone size but not with serum creatinine in patients with obstructing ureterolithiasis.

Previous reports show increased severity of perinephric fat stranding (PFS) with elevated serum creatinine in obstructing ureterolithiasis. We sought to investigate this association with our institution's patient population.We reviewed charts of patients diagnosed with obstructive ureterolithiasis or nephrolithiasis in our emergency department between January and October 2018. Patient demographics, lab results, and computed tomography (CT) imaging were reviewed. A blinded radiologist reviewed all CTs and graded hydronephrosis and PFS. Subjects were stratified by degree of PFS and compared via paired t-test, chi-squared test, univariate analysis, and multivariate analysis.We identified 141 patients; 114 had no-mild (Group 1) PFS, while 27 had moderate-severe (Group 2) PFS. Group 1 had a mean age of 56 (SD = 16.1) and mean stone size of 7.3 mm (SD = 4.22); 77% of the cohort had symptoms under 24 h. Group 2 was older with a mean age of 65 (SD = 16.2, p = 0.01) and mean stone size of 10.1 mm (SD = 6.07, p < 0.01); 50% had symptoms less than 24 h (p = 0.01). PFS did not correlate with change in serum creatinine. Univariate and multivariate analysis showed increasing age increased the odds of moderate-severe PFS by 3.5% (OR = 1.035, p < 0.05) while increased stone size increased the odds of moderate-severe PFS by 13.7% (OR = 1.137, p = 0.01).Although increased PFS correlated with increased age and stone size, no correlation was found with presenting creatinine or change in creatinine. Degree of PFS is likely a poor predictor of renal disease severity in acute ureterolithiasis.

CT-based muscle and adipose measurements predict prognosis in patients with digestive system malignancy.

The role of skeletal muscle and adipose tissue in the progression of cancer has been gradually discussed, but it needs further exploration. The objective of this study was to provide an in-depth analysis of skeletal muscle and fat in digestive malignancies and to construct novel predictors for clinical management. This is a retrospective study that includes data from Cancer Center, the First Hospital of Jilin University. Basic characteristic information was analyzed by T tests. Correlation matrices were drawn to explore the relationship between CT-related indicators and other indicators. Cox risk regression analyses were performed to analyze the association between the overall survivals (OS) and various types of indicators. A new indicator body composition score (BCS) was then created and a time-dependent receiver operating characteristic curve was plotted to analyze the efficacy of the BCS. Finally, a nomogram was produced to develop a scored-CT system based on BCS and other indicators. C-index and calibration curve analyses were performed to validate the predictive accuracy of the scored-CT system. A total of 575 participants were enrolled in the study. Cox risk regression model revealed that VFD, L3 SMI and VFA/SFA were associated with prognosis of cancer patients. After adjustment, BCS index based on CT was significantly associated with prognosis, both in all study population and in subgroup analysis according to tumor types (all study population: HR 2.036, P < 0.001; colorectal cancer: HR 2.693, P < 0.001; hepatocellular carcinoma: HR 4.863, P < 0.001; esophageal cancer: HR 4.431, P = 0.008; pancreatic cancer: HR 1.905, P = 0.016; biliary system malignancies: HR 23.829, P = 0.035). The scored-CT system was constructed according to tumor type, stage, KPS, PG-SGA and BCS index, and it was of great predictive validity. This study identified VFD, L3 SMI and VFA/SFA associated with digestive malignancies outcomes. BCS was created and the scored-CT system was established to predict the OS of cancer patients.

Association of myosteatosis with short-term outcomes in patients with acute-on-chronic liver failure.

Sarcopenia (low muscle mass, i.e., quantity) is associated with poor clinical outcomes in patients with acute-on-chronic liver failure (ACLF). In this study, we aimed to illustrate the clinical prognostic value of myosteatosis (muscle fat infiltration) for short-term mortality in patients with ACLF. We retrospectively enrolled consecutive patients with ACLF between January 2019 and January 2022. Computed tomography-based body composition analysis was performed at the third lumbar vertebral level to determine skeletal muscle radiation attenuation. Fine and Gray's competing risk regression model, with liver transplantation as a competing risk, was used to assess the factors associated with 90-day mortality. A total of 431 patients with ACLF were included. Myosteatosis and sarcopenia were observed in 261 (60.6%) and 87 (20.2%) patients, respectively. Competitive risk regression showed that age (HR 1.021, 95% CI 1.000-1.043, P = 0.042), APASL ACLF Research Consortium (AARC) score (HR 1.498, 95% CI 1.312-1.710, P < 0.001), and sarcopenia (HR 1.802, 95% CI 1.062-3.060, P = 0.029) were independently associated with increased 90-day mortality. Subgroup analysis of male patients with HBV-ACLF revealed that myosteatosis (HR 2.119, 95% CI 1.101-4.078, P = 0.025) was promising prognostic factors for 90-day mortality after being adjusted for ascites, acute kidney injury, AARC score, and sarcopenia. Myosteatosis is predictive of short-term outcomes in male patients with HBV-ACLF. Our results emphasise the importance of focusing on muscle fat infiltration in patients with HBV-ACLF. Further studies are warranted to investigate the underlying mechanisms and potential therapies for myosteatosis.

Primary disease of adipose tissue: When to think about and how to evaluate it in clinical practice?

Primary diseases of adipose tissue are rare disorders resulting from impairments in the physiological functions of adipose tissue (lipid stockage and endocrine function). It mainly refers to lipodystrophy syndromes with subcutaneous adipose tissue atrophy and/or altered body distribution of adipose tissue leading to insulin resistance, diabetes, hepatic steatosis, dyslipidemia, cardiovascular complications and polycystic ovary syndrome in women. Those syndromes are congenital or acquired, and lipoatrophy is partial or generalized. The diagnosis of lipodystrophy syndromes is often unrecognized, delayed and/or inaccurate, while it is of major importance to adapt investigations to search for specific comorbidities, in particular cardiovascular involvement, and set up multidisciplinary care, and in some cases specific treatment. Physicians have to recognize the clinical and biological elements allowing to establish the diagnosis. Lipodystrophic syndromes should be considered, notably, in patients with diabetes at a young age, with a normal or low BMI, negative pancreatic autoantibodies, presenting clinical signs of lipodystrophy and insulin resistance (acanthosis nigricans, hyperandrogenism, hepatic steatosis, high insulin doses). The association of diabetes and a family history of severe and/or early cardiovascular disease (coronary atherosclerosis, cardiomyopathy with rhythm and/or conduction disorders) may reveal Dunnigan syndrome, the most frequent form of familial lipodystrophy, due to LMNA pathogenic variants. Clinical assessment is primarily done through clinical examination: acanthosis nigricans, abnormal adipose tissue distribution, lipoatrophy, muscular hypertrophy, acromegaloid or Cushingoid features, lipomas, highly visible subcutaneous veins, may be revealing signs. The amount of circulating adipokines may reflect of adipose dysfunction with low leptinemia and adiponectinemia. Other biological metabolic parameters (hypertriglyceridemia, hyperinsulinemia, increased glycemia and hepatic enzymes) may also represent markers of insulin resistance. Quantification of total body fat by impedancemetry or dual-photon X-ray absorptiometry (DEXA) reveals decreased total body mass, in correlation with adipose tissue atrophy; metabolic magnetic resonance imaging can also quantify intraperitoneal and abdominal fat and the degree of hepatic steatosis. Histological analysis of adipose tissue showing structural abnormalities should be reserved for clinical research. Acquired lipodystrophic syndromes most often lead to similar clinical phenotype as congenital syndromes with generalized or partial lipoatrophy. The most frequent causes are old anti-HIV therapy or glucocorticoid treatments. Family history, history of treatments and clinical examination, including a careful physical examination, are keys for diagnosis.