Limited fasciectomy with versus without autologous adipose tissue grafting for treatment of Dupuytren's contracture (REMEDY): study protocol for a multicentre randomised controlled trial.

BACKGROUND: Dupuytren's contracture is a hereditary disorder which causes progressive fibrosis of the palmar aponeurosis of the hand, resulting in digital flexion contractures of the affected rays. Limited fasciectomy is a standard surgical treatment for Dupuytren's, and the one with the lowest recurrence rate; however, the recurrence is still relatively high (2-39%). Adipose-derived stem cells have been shown to inhibit Dupuytren's myofibroblasts proliferation and contractility in vitro, as well as to improve scar quality and skin regeneration in different types of surgeries. Autologous adipose tissue grafting has already been investigated as an adjuvant treatment to percutaneous needle fasciotomy for Dupuytren's contracture with good results, but it was only recently associated with limited fasciectomy. The purpose of REMEDY trial is to investigate if limited fasciectomy with autologous adipose tissue grafting would decrease recurrence compared to limited fasciectomy alone. METHODS: The REMEDY trial is a multi-centre open-label randomised controlled trial (RCT) with 1:1 allocation ratio. Participants (n = 150) will be randomised into two groups, limited fasciectomy with autologous adipose tissue grafting versus limited fasciectomy alone. The primary outcome is the recurrence of Dupuytren's contracture on any of the treated rays at 2 years postoperatively. The secondary outcomes are recurrence at 3 and 5 years, scar quality, complications, occurrence of algodystrophy (complex regional pain syndrome), patient-reported hand function, and hypodermal adipose tissue loss at 1 year postoperatively in a small subset of patients. DISCUSSION: The REMEDY trial is one of the first studies investigating limited fasciectomy associated with autologous adipose tissue grafting for Dupuytren's contracture, and, to our knowledge, the first one investigating long-term outcomes of this treatment. It will provide insight into possible benefits of combining adipose tissue grafting with limited fasciectomy, such as lower recurrence rate and improvement of scar quality. TRIAL REGISTRATION: ClinicalTrials.gov NCT05067764, June 13, 2022.

Understanding and controlling the variables for stromal vascular fraction therapy.

In regenerative medicine, the isolation of mesenchymal stromal cells (MSCs) from the adipose tissue's stromal vascular fraction (SVF) is a critical area of study. Our review meticulously examines the isolation process of MSCs, starting with the extraction of adipose tissue. The choice of liposuction technique, anatomical site, and immediate processing are essential to maintain cell functionality. We delve into the intricacies of enzymatic digestion, emphasizing the fine-tuning of enzyme concentrations to maximize cell yield while preventing harm. The review then outlines the filtration and centrifugation techniques necessary for isolating a purified SVF, alongside cell viability assessments like flow cytometry, which are vital for confirming the efficacy of the isolated MSCs. We discuss the advantages and drawbacks of using autologous vs allogeneic SVF sources, touching upon immunocompatibility and logistical considerations, as well as the variability inherent in donor-derived cells. Anesthesia choices, the selection between hypodermic needles vs liposuction cannulas, and the role of adipose tissue lysers in achieving cellular dissociation are evaluated for their impact on SVF isolation. Centrifugation protocols are also analyzed for their part in ensuring the integrity of the SVF. The necessity for standardized MSC isolation protocols is highlighted, promoting reproducibility and successful clinical application. We encourage ongoing research to deepen the understanding of MSC biology and therapeutic action, aiming to further the field of regenerative medicine. The review concludes with a call for rigorous research, interdisciplinary collaboration, and strict adherence to ethical and regulatory standards to safeguard patient safety and optimize treatment outcomes with MSCs.

DNA Methyltransferase Inhibition by RG108 Improves Stemness and Multipotential Differentiation of Human Adipose Tissue-derived Stem Cells.

Background: DNA methylation plays important roles in regulating various biological processes, including self-renewal, differentiation and regenerative capacity of stem cells. Previous studies have demonstrated that lineage-specific differentiation of mesenchymal stem cells can be promoted using nontoxic chromatin-modifying drugs. Objectives: Here we evaluated the impact of RG108, a known DNA methyltransferase inhibitor, on the expression of pluripotency genes in human adipose tissue-derived stem cells (hADSCs) and their proliferation and differentiation. Materials and Methods: Human ADSCs were isolated by collagenase treatment and characterized. Then, ADSCs were treated with 5 µM RG108 for four days. The control and RG108-treated cells were analyzed for the cell cycle progression, apoptosis and the expression of pluripotency genes. Also, ADSCs were cultured in adipogenic and osteogenic differentiation media for three weeks and were assessed by Oil Red O and Alizarin Red S staining and qPCR analysis. Results: We showed that RG108 treatment increased proliferation of hADSCs and upregulated the expression of pluripotency-related genes. Additionally, RG108 had a positive impact on the differentiation capability of ADSCs. This was evident through elevated levels of Oil Red O staining in the RG108 treatment group. Also, qPCR analysis showed the upregulation of some adipogenic and osteogenic markers by RG108. Conclusion: These findings indicate that pretreatment with RG108 improves the differentiation potential of ADSCs, probably making these cells more beneficial for cell therapy applications.

Contents of exosomes derived from adipose tissue and their regulation on inflammation, tumors, and diabetes.

Adipose tissue (AT) serves as an energy-capacitive organ and performs functions involving paracrine- and endocrine-mediated regulation via extracellular vesicles (EVs) secretion. Exosomes, a subtype of EVs, contain various bioactive molecules with regulatory effects, such as nucleic acids, proteins, and lipids. AT-derived exosomes (AT-exos) include exosomes derived from various cells in AT, including adipocytes, adipose-derived stem cells (ADSCs), macrophages, and endothelial cells. This review aimed to comprehensively evaluate the impacts of different AT-exos on the regulation of physiological and pathological processes. The contents and functions of adipocyte-derived exosomes and ADSC-derived exosomes are compared simultaneously, highlighting their similarities and differences. The contents of AT-exos have been shown to exert complex regulatory effects on local inflammation, tumor dynamics, and insulin resistance. Significantly, differences in the cargoes of AT-exos have been observed among diabetes patients, obese individuals, and healthy individuals. These differences could be used to predict the development of diabetes mellitus and as therapeutic targets for improving insulin sensitivity and glucose tolerance. However, further research is needed to elucidate the underlying mechanisms and potential applications of AT-exos.

Exercise-Induced cytokines, diet, and inflammation and their role in adipose tissue metabolism.

Background: Obesity poses a significant global health challenge, necessitating effective prevention and treatment strategies. Exercise and diet are recognized as pivotal interventions in combating obesity. This study reviews the literature concerning the impact of exercise-induced cytokines, dietary factors, and inflammation on adipose tissue metabolism, shedding light on potential pathways for therapeutic intervention. Methodology: A comprehensive review of relevant literature was conducted to elucidate the role of exercise-induced cytokines, including interleukin-6 (IL-6), interleukin-15 (IL-15), brain-derived neurotrophic factor (BDNF), irisin, myostatin, fibroblast growth factor 21 (FGF21), follistatin (FST), and angiopoietin-like 4 (ANGPTL4), in adipose tissue metabolism. Various databases were systematically searched using predefined search terms to identify relevant studies. Articles selected for inclusion underwent thorough analysis to extract pertinent data on the mechanisms underlying the influence of these cytokines on adipose tissue metabolism. Results and Discussion: Exercise-induced cytokines exert profound effects on adipose tissue metabolism, influencing energy expenditure (EE), thermogenesis, fat loss, and adipogenesis. For instance, IL-6 activates AMP-activated protein kinase (AMPK), promoting fatty acid oxidation and reducing lipogenesis. IL-15 upregulates peroxisome proliferator-activated receptor delta (PPARδ), stimulating fatty acid catabolism and suppressing lipogenesis. BDNF enhances AMPK-dependent fat oxidation, while irisin induces the browning of white adipose tissue (WAT), augmenting thermogenesis. Moreover, myostatin, FGF21, FST, and ANGPTL4 each play distinct roles in modulating adipose tissue metabolism, impacting factors such as fatty acid oxidation, adipogenesis, and lipid uptake. The elucidation of these pathways offers valuable insights into the complex interplay between exercise, cytokines, and adipose tissue metabolism, thereby informing the development of targeted obesity management strategies. Conclusion: Understanding the mechanisms by which exercise-induced cytokines regulate adipose tissue metabolism is critical for devising effective obesity prevention and treatment modalities. Harnessing the therapeutic potential of exercise-induced cytokines, in conjunction with dietary interventions, holds promise for mitigating the global burden of obesity. Further research is warranted to delineate the precise mechanisms underlying the interactions between exercise, cytokines, and adipose tissue metabolism.

Impact of epicardial adipose tissue on diastolic dysfunction in patients with chronic coronary syndrome and preserved left ventricular ejection fraction.

Aims: This study aims to investigate the association between left ventricular diastolic dysfunction (LVDD) and epicardial adipose tissue (EAT) accumulation in patients with chronic coronary syndrome (CCS) and preserved left ventricular ejection fraction (LVEF). Methods and results: The study included 314 patients with preserved LVEF who underwent coronary computed tomographic angiography (CCTA) and thoracic tissue Doppler echocardiography (TTDE). The EAT volume was measured using CCTA. LVDD was categorized into three groups: absent LVDD, undetermined LVDD, and LVDD. Multivariate logistic regression analysis was performed to assess the association between the clinical parameters, TTDE and CCTA findings, and LVDD. Patients (mean age: 66 ± 13 years; 52% men) were divided into LVDD present (30 patients, 9.6%), LVDD absent (219 patients, 69.7%), and LVDD undetermined (65 patients, 20.7%) groups. CCTA showed that patients with LVDD had a significantly higher coronary artery calcium (CAC) score and % plaque volume (%PV) than those without LVDD, whereas the prevalence of obstructive coronary artery disease was comparable between the groups. The EAT volume index correlated with each LVDD diagnostic component, except for tricuspid regurgitation velocity. A multivariate model showed that age [odds ratio (OR), 1.13; P < 0.001] and EAT volume index (OR, 1.02; P = 0.038) were independently associated with LVDD, even after adjusting for left ventricular mass index (OR, 1.05; P = 0.005). There was no significant association between the CAC score and %PV or LVDD. Conclusion: This study demonstrated that EAT volume index and left ventricular mass index were robust predictors of LVDD; however, there was no independent association between coronary atherosclerotic disease burden and LVDD.

The epicardial adipose tissue confined in the atrioventricular groove can be used to assess atrial adipose tissue and atrial dysfunction in cardiac magnetic resonance imaging.

Aims: The growing interest in epicardial adipose tissue (EAT) as a biomarker of atrial fibrillation is limited by the difficulties in isolating EAT from other paracardial adipose tissues. We tested the feasibility and value of measuring the pure EAT contained in the atrioventricular groove (GEAT) using cardiovascular magnetic resonance (CMR) imaging in patients with distinct metabolic disorders. Methods and results: CMR was performed on 100 patients from the MetaCardis cohort: obese (n = 18), metabolic syndrome (MSD) (n = 25), type-2 diabetes (T2D) (n = 42), and age- and gender-matched healthy controls (n = 15). GEAT volume measured from long-axis views was obtained in all patients with a strong correlation between GEAT and atrial EAT (r = 0.95; P < 0.0001). GEAT volume was higher in the three groups of patients with metabolic disorders and highest in the MSD group compared with controls. GEAT volume, as well as body mass and body fat, allowed obese, T2D, and MSD patients to be distinguished from controls. GEAT T1 relaxation and peak longitudinal left atrial (LA) strain in CMR were decreased in T2D patients. Logistic regression and random forest machine learning methods were used to create an algorithm combining GEAT volume, GEAT T1, and peak LA strain to identify T2D patients from other groups with an area under curve (AUC) of 0.81 (Se: 77%, Spe: 80%; 95% confidence interval 0.72-0.91, P < 0.0001). Conclusion: Atrioventricular groove adipose tissue characteristics measured during routine CMR can be used as a proxy of atrial EAT and integrated in a multi-parametric CMR biomarker for early identification of atrial cardiomyopathy.

The effects of exercise on microRNA expression profiling in adipose tissue macrophages of mice.

Background: Exercise is recognized for its broad health benefits, influencing various physiological processes, including the behavior of adipose tissue macrophages (ATMs). While existing studies mainly associate ATM activity with obesity and metabolic syndrome, our study explores the impact of aerobic exercise on ATM microRNA expression profiling in a non-obese context, highlighting its general health-promoting mechanisms. Methods: Sixty male C57BL/6 mice were randomly assigned to either a sedentary (S) or an exercise (E) group. The S group remained inactive, while the E group underwent a one-week treadmill adaptation, followed by an 8-week aerobic treadmill exercise protocol (60 min/day, 5 days/week, at 65%-75% VO2max). Post-training, glucose tolerance and the serum lipid levels were measured in mice subjected to both exercise and non-exercise conditions. ATMs harvested from visceral adipose tissues were analyzed and sorted using flow cytometer. To further investigate the effects of exercise in ATMs at the molecular level, miRNA microarray analysis was performed, followed by bioinformatic analysis. Results: The 8-week regimen of moderate-intensity aerobic exercise ameliorated glucolipid metabolism and fostered a dynamic shift toward an M2 macrophage phenotype in the adipose tissue, independent of obesity. A total of 62 differentially expressed miRNAs were identified in ATMs of mice post-exercise. Notably, six miRNAs (miR-212-5p, miR-511-5p, miR-7b-5p, miR-142-3p, miR-1894-3p, and miR-31-5p) as well as their target gene were consistently altered and associated with macrophage polarization and metabolic regulation. Conclusion: Our findings broaden the understanding of how exercise regulates ATM functions through significant changes in microRNA profiles, emphasizing its potential to enhance health and prevent chronic conditions. This study supports the application of aerobic exercise for its preventive effects on chronic diseases and underscores the importance of microRNA profiling in understanding the immune-modulatory impacts of exercise.

Epigenetic profiles in blood and adipose tissue: identifying strong correlations in morbidly obese and non-obese patients.

Epigenetic alterations play a pivotal role in conditions influenced by environmental factors such as overweight and obesity. Many of these changes are tissue-specific, which entails a problem in its study since obtaining human tissue is a complex and invasive practice. While blood is widely used as a surrogate biomarker, it cannot directly extrapolate the evidence found in blood to tissue. Moreover, the intricacies of metabolic diseases add a new layer of complexity, as obesity leads to significant alterations in adipose tissue, potentially causing associated pathologies that can disrupt existing correlations seen in healthy individuals. Here, our objective was to determine which epigenetic markers exhibit correlations between blood and adipose tissue, regardless of the metabolic status. We collected paired blood and adipose tissue samples from 64 patients with morbidity obesity and non-obese and employed the MethylationEPIC 850 K array for analysis. We found that only a small fraction, specifically 4.3% (corresponding to 34,825 CpG sites), of the sites showed statistically significant correlations (R ≥ 0.6) between blood and adipose tissue. Within this subset, 5327 CpG sites exhibited a strong correlation (R ≥ 0.8) between blood and adipose tissue. Our findings suggest that the majority of epigenetic markers in peripheral blood do not reliably reflect changes occurring in visceral adipose tissues. However, it is important to note that there exists a distinct set of epigenetic markers that can indeed mirror changes in adipose tissue within blood samples. KEY MESSAGES: More than 8% of methylation sites exhibit similarity between blood and adipose tissues, regardless of BMI The correlation percentage between blood and adipose tissue is strongly influenced by gender The principal genes implicated in this correlation are related to metabolism or the immunological system.

Adherence to dietary approaches to stop hypertension diet and visceral adipose tissue area among U.S. adults, a cross-sectional study.

Excessive visceral adipose tissue (VAT) is a significant risk factor for various diseases. Diet plays a crucial role in controlling obesity. This study examined the association between the Dietary Approaches to Stop Hypertension (DASH) diet and VAT in 9027 adults using data from the National Health and Nutrition Examination Survey. Linear regression models were used to explore this association, with subgroup analyses included. Results showed a significant inverse association between DASH scores and VAT area, even after adjusting for covariates (ß = -2.18, 95% CI: -3.10, -1.27). Participants in the highest DASH score tertile had significantly lower VAT areas compared to those in the lowest tertile (ß = -7.2, 95% CI: -10.40, -4.01). This inverse association was most pronounced in middle-aged participants. Further prospective cohort studies are necessary to confirm these findings.

Adipose tissue-derived adipsin marks human aging in non-type 2 diabetes population.

INTRODUCTION: Adipsin or complement factor D is an adipokine that augments insulin secretion, is altered in various degrees of obesity, and is involved in alternative complement pathway. However, whether adipsin has any independent association with risk factors and biomarkers in patients with type 2 diabetes (T2D) remains elusive. RESEARCH DESIGN AND METHODS: We performed an oral glucose tolerance test on a subset of 43 patients with T2D from the community health cohort to access the role of adipsin in insulin secretion. We further cross-sectionally examined the role of adipsin in plasma, adipose tissue (AT), and secretion in a community cohort of 353 subjects and a hospital cohort of 52 subjects. RESULTS: We found that plasma adipsin has no significant correlation with insulin secretion in people with diabetes. Among the risk factors of T2D, adipsin levels were independently associated only with age, and a positive correlation between plasma adipsin and age among subjects without T2D was lost in patients with T2D. Plasma adipsin levels, AT adipsin expression, and secretion were upregulated both in T2D and aging, with a corresponding drop in Homeostatic Model Assessment for assessing ß-cell function. Adipsin expression was positively associated with other aging biomarkers, such as ß-galactosidase, p21, and p16. These results also corroborated with existing plasma proteomic signatures of aging, including growth, and differentiation factor-15, which strongly correlated with adipsin. CONCLUSIONS: Our results demonstrate an increase in circulating adipsin in T2D and aging, and it scores as a candidate plasma marker for aging specifically in non-T2D population.

Eriodictyol regulates white adipose tissue browning and hepatic lipid metabolism in high fat diet-induced obesity mice via activating AMPK/SIRT1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Blossom of Citrus aurantium L. var. amara Engl. (CAVA) has been popularly consumed as folk medicine and dietary supplement owing to its various beneficial effects and especially anti-obesity potential. Our previous study predicted that eriodictyol was probably one of the key active compounds of the total flavonoids from blossom of CAVA. However, effects of eriodictyol in anti-obesity were still elusive. AIM OF THE STUDY: This study was performed to explore the precise role of eriodictyol in white adipose tissue (WAT) browning and hepatic lipid metabolism, and simultaneously, to verify the impact of eriodictyol on the total flavonoids of CAVA in losing weight. MATERIALS AND METHODS: The pancreas lipase assay was conducted and oleic acid-induced HepG2 cells were established to preliminarily detect the lipid-lowering potential of eriodictyol. Then, high fat diet-induced obesity (DIO) mouse model was established for in vivo studies. The biochemical indicators of mice were tested by commercial kits. The histopathological changes of WAT and liver in mice were tested by H&E staining, Oil Red O staining and Sirius Red staining. Immunohistochemical, western blot assay, as well as RT-qPCR analysis were further performed. Additionally, molecular docking assay was used to simulate the binding of eriodictyol with potential target proteins. RESULTS: In vitro studies showed that eriodictyol intervention potently inhibited pancreatic lipase activity and reversed hepatic steatosis in oleic acid-induced HepG2 cells. Consistently, long-term medication of eriodictyol also effectively prevented obesity and improved lipid and glucose metabolism in diet-induced obesity (DIO) mice. Obesity-induced histopathological changes in iWAT, eWAT and BAT, and abnormal expression levels of IL-10, IL-6 and TNF-α in iWAT of DIO mice were also significantly reversed by eriodictyol treatment. Eriodictyol administration significantly and potently promoted browning of iWAT by increasing expression levels of thermogenic marker protein of UCP1, as well as brown adipocyte-specific genes of PGC-1α, SIRT1 and AMPKα1. Further assays revealed that eriodictyol enhanced mitochondrial function, as shown by an increase in compound IV activity and the expression of tricarboxylic acid cycle-related genes. Besides, eriodictyol addition markedly reversed hepatic damages and hepatic inflammation, and enhanced hepatic lipid metabolism in DIO mice, as evidenced by its regulation on p-ACC, CPT1-α, UCP1, PPARα, PGC-1α, SIRT1 and p-AMPKα expression. Molecular docking results further validated that AMPK/SIRT1 pathway was probably the underlying mechanisms by which eriodictyol acted. CONCLUSION: Eriodictyol exhibited significant anti-obesity effect, which was comparable to that of the total flavonoids from blossom of CAVA. These findings furnished theoretical basis for the application of eriodictyol in weight loss.

TLCD4 as Potential Transcriptomic Biomarker of Cold Exposure.

(1) Background: Cold exposure induces metabolic adaptations that can promote health benefits, including increased energy disposal due to lipid mobilization in adipose tissue (AT). This study aims to identify easily measurable biomarkers mirroring the effect of cold exposure on AT. (2) Methods: Transcriptomic analysis was performed in peripheral blood mononuclear cells (PBMCs) and distinct AT depots of two animal models (ferrets and rats) exposed to cold, and in PBMCs of cold-exposed humans. (3) Results: One week of cold exposure (at 4 °C) affected different metabolic pathways and gene expression in the AT of ferrets, an animal model with an AT more similar to humans than that of rodents. However, only one gene, Tlcd4, was affected in the same way (overexpressed) in aortic perivascular and inguinal AT depots and in PBMCs, making it a potential biomarker of interest. Subsequent targeted analysis in rats showed that 1 week at 4 °C also induced Tlcd4 expression in brown AT and PBMCs, while 1 h at 4 °C resulted in reduced Tlcd4 mRNA levels in retroperitoneal white AT. In humans, no clear effects were observed. Nevertheless, decreased PBMC TLCD4 expression was observed after acute cold exposure in women with normal weight, although this effect could be attributed to short-term fasting during the procedure. No effect was evident in women with overweight or in normal-weight men. (4) Conclusions: Our results obtained for different species point toward TLCD4 gene expression as a potential biomarker of cold exposure/fat mobilization that could tentatively be used to address the effectiveness of cold exposure-mimicking therapies.

Adipose Tissue: A Novel Target of the Incretin Axis? A Paradigm Shift in Obesity-Linked Insulin Resistance.

Adipose tissue (AT) represents a plastic organ that can undergo significant remodeling in response to metabolic demands. With its numerous checkpoints, the incretin system seems to play a significant role in controlling glucose homeostasis and energy balance. The importance of the incretin hormones, namely the glucagon-like peptide-1 (GLP-1) and the glucose-dependent insulinotropic peptide (GIP), in controlling the function of adipose cells has been brought to light by recent studies. Notably, a "paradigm shift" in reevaluating the role of the incretin system in AT as a potential target to treat obesity-linked metabolic disorders resulted from the demonstration that a disruption of the GIP and GLP-1 signaling axis in fat is associated with adiposity-induced insulin-resistance (IR) and/or type 2 diabetes mellitus (T2D). We will briefly discuss the (patho)physiological functions of GLP-1 and GIP signaling in AT in this review, emphasizing their potential impacts on lipid storage, adipogenesis, glucose metabolism and inflammation. We will also address the conundrum with the perturbation of the incretin axis in white or brown fat tissue and the emergence of metabolic disorders. In order to reduce or avoid adiposity-related metabolic complications, we will finally go over a potential scientific rationale for suggesting AT as a novel target for GLP-1 and GIP receptor agonists and co-agonists.

Glycerol Handling in Paired Visceral and Subcutaneous Adipose Tissues in Women with Normal Weight and Upper-Body Obesity.

In adipose tissue, reduced expression of the glycerol channel aquaporin 7 (AQP7) has been associated with increased accumulation of triglyceride. The present study determines the relative protein abundances of lipolytic enzymes, AQP7, and cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in paired mesenteric and omental visceral adipose tissue (VAT) and abdominal and femoral subcutaneous adipose tissue (SAT) in women with either normal weight or upper-body obesity. No differences in the expression of hormone-sensitive lipase (HSL) or AQP7 were found between the two groups in the four depots. The expression of adipocyte triglyceride lipase (ATGL) and HSL were higher in omental VAT and femoral SAT than in mesenteric VAT in both groups of women. Similarly, AQP7 expression was higher in omental VAT than in mesenteric VAT. The expression of PEPCK-C was lower in omental VAT than in femoral SAT. No correlation between the expression of AQP7 and the mean adipocyte size was observed; however, the expression of PEPCK-C positively correlated with the mean adipocyte size. In conclusion, a depot-specific protein expression pattern was found for ATGL, HSL, AQP7, and PEPCK-C. The expression pattern supports that the regulation of AQP7 protein expression is at least in part linked to the lipolytic rate. Furthermore, the results support that the synthesis of glycerol-3-phosphate via glyceroneogenesis contributes to regulating triglyceride accumulation in white adipose tissue in women.

A Closer Look into White Adipose Tissue Biology and the Molecular Regulation of Stem Cell Commitment and Differentiation.

White adipose tissue (WAT) makes up about 20-25% of total body mass in healthy individuals and is crucial for regulating various metabolic processes, including energy metabolism, endocrine function, immunity, and reproduction. In adipose tissue research, "adipogenesis" is commonly used to refer to the process of adipocyte formation, spanning from stem cell commitment to the development of mature, functional adipocytes. Although, this term should encompass a wide range of processes beyond commitment and differentiation, to also include other stages of adipose tissue development such as hypertrophy, hyperplasia, angiogenesis, macrophage infiltration, polarization, etc.… collectively, referred to herein as the adipogenic cycle. The term "differentiation", conversely, should only be used to refer to the process by which committed stem cells progress through distinct phases of subsequent differentiation. Recognizing this distinction is essential for accurately interpreting research findings on the mechanisms and stages of adipose tissue development and function. In this review, we focus on the molecular regulation of white adipose tissue development, from commitment to terminal differentiation, and examine key functional aspects of WAT that are crucial for normal physiology and systemic metabolic homeostasis.

Diagnosing Sarcopenia with AI-Aided Ultrasound (DINOSAUR)-A Pilot Study.

Background: Sarcopenia has been recognized as a determining factor in surgical outcomes and is associated with an increased risk of postoperative complications and readmission. Diagnosis is currently based on clinical guidelines, which includes assessment of skeletal muscle mass but not quality. Ultrasound has been proposed as a useful point-of-care diagnostic tool to assess muscle quality, but no validated cut-offs for sarcopenia have been reported. Using novel automated artificial intelligence (AI) software to interpret ultrasound images may assist in mitigating the operator-dependent nature of the modality. Our study aims to evaluate the fidelity of AI-aided ultrasound as a reliable and reproducible modality to assess muscle quality and diagnose sarcopenia in surgical patients. Methods: Thirty-six adult participants from an outpatient clinic were recruited for this prospective cohort study. Sarcopenia was diagnosed according to Asian Working Group for Sarcopenia (AWGS) 2019 guidelines. Ultrasonography of the rectus femoris muscle was performed, and images were analyzed by an AI software (MuscleSound® (Version 5.69.0)) to derive muscle parameters including intramuscular adipose tissue (IMAT) as a proxy of muscle quality. A receiver operative characteristic (ROC) curve was used to assess the predictive capability of IMAT and its derivatives, with area under the curve (AUC) as a measure of overall diagnostic accuracy. To evaluate consistency between ultrasound users of different experience, intra- and inter-rater reliability of muscle ultrasound parameters was analyzed in a separate cohort using intraclass correlation coefficients (ICC) and Bland-Altman plots. Results: The median age was 69.5 years (range: 26-87), and the prevalence of sarcopenia in the cohort was 30.6%. The ROC curve plotted with IMAT index (IMAT% divided by muscle area) yielded an AUC of 0.727 (95% CI: 0.551-0.904). An optimal cut-off point of 4.827%/cm2 for IMAT index was determined with a Youden's Index of 0.498. We also demonstrated that IMAT index has excellent intra-rater reliability (ICC = 0.938, CI: 0.905-0.961) and good inter-rater reliability (ICC = 0.776, CI: 0.627-0.866). In Bland-Altman plots, the limits of agreement were from -1.489 to 1.566 and -2.107 to 4.562, respectively. Discussion: IMAT index obtained via ultrasound has the potential to act as a point-of-care evaluation for sarcopenia screening and diagnosis, with good intra- and inter-rater reliability. The proposed IMAT index cut-off maximizes sensitivity for case finding, supporting its use as an easily implementable point-of-care test in the community for sarcopenia screening. Further research incorporating other ultrasound parameters of muscle quality may provide the basis for a more robust diagnostic tool to help predict surgical risk and outcomes.

Agave-Laurate-Bioconjugated Fructans Decrease Hyperinsulinemia and Insulin Resistance, Whilst Increasing IL-10 in Rats with Metabolic Syndrome Induced by a High-Fat Diet.

Metabolic syndrome (MetS) comprises a cluster of metabolic risk factors, which include obesity, hypertriglyceridemia, high blood pressure, and insulin resistance. The purpose of this study was to evaluate the effects of laurate-bioconjugated fructans on pro- and anti-inflammatory cytokines in Wistar rats with MetS induced by a high-fat diet. Laurate-bioconjugated fructans were synthesized with agave fructans, immobilized lipase B, and vinyl laureate as the acylant. Groups were fed a standard diet (NORMAL), a high-fat diet (HFD), or a high-fat diet plus laurate-bioconjugated fructans (FL PREV) for 9 weeks. A fourth group received a high-fat diet for 6 weeks, followed by simultaneous exposure to a high-fat diet and laurate-bioconjugated fructans for 3 additional weeks (FL REV). The dose of laurate-bioconjugated fructans was 130 mg/kg. Laurate-bioconjugated fructans reduced food and energy intake, body weight, body mass index, abdominal circumference, adipose tissue, adipocyte area, serum triglycerides, insulin, insulin resistance, and C-reactive protein but they increased IL-10 protein serum levels and mRNA expression. The impact of laurate-bioconjugated fructans on zoometric and metabolic parameters supports their potential as therapeutic agents to improve obesity, obesity comorbidities, insulin resistance, type 2 diabetes mellitus, and MetS.

Natriuretic peptide receptor-C perturbs mitochondrial respiration in white adipose tissue.

Natriuretic peptide receptor-C (NPR-C) is highly expressed in adipose tissues, and regulates obesity related diseases, however the detailed mechanism remains unknown. In this research, we aimed to explore the potential role of NPR-C in cold exposure and high-fat/high-sugar (HF/HS) diet induced metabolic changes, especially in regulating white adipose tissue (WAT) mitochondrial function. Our findings showed that NPR-C expression, especially in epididymal WAT (eWAT), was reduced after cold exposure. Global Npr3 (gene encoding NPR-C protein) deficiency led to reduced body weight, increased WAT browning, thermogenesis, and enhanced expression of genes related to mitochondrial biogenesis. RNA-sequencing of eWAT showed that Npr3 deficiency enhanced expression of mitochondrial respiratory chain complex genes and promoted mitochondrial oxidative phosphorylation in response to cold exposure. In addition, Npr3 KO mice were able to resist obesity induced by HF/HS diet. Npr3 knockdown in stromal vascular fraction (SVF)-induced white adipocytes promoted the expression of proliferator-activated receptor gamma coactivator 1α (PGC1α), uncoupling protein 1 (UCP1) and mitochondrial respiratory chain complexes. Mechanistically, NPR-C inhibited cGMP and calcium signaling in an NPR-B-dependent manner but suppressed cAMP signaling in an NPR-B-independent manner. Moreover, Npr3 knockdown induced browning via AKT and p38 pathway activation, which were attenuated by Npr2 knockdown. Importantly, treatment with the NPR-C specific antagonist, AP-811, decreased WAT mass and increased PGC-1α, UCP1 and mitochondrial complex expression. These findings demonstrate that NPR-C deficiency enhances metabolic health by boosting energy expenditure in WAT, emphasizing the potential of NPR-C inhibition for treating obesity and related metabolic disorders.

Developmental overlap between skeletal muscle maturation and perirenal fat brown-to-white transition in goats: Exploring the role of Myf-5.

In mammals, skeletal muscles (SkMs) and adipose tissues regulate energy homeostasis and share developmental origins. Notably, the perirenal adipose tissue (PRAT) depot has been reported to display adipocyte heterogeneity: while some originated from Myogenic factor 5 (Myf-5) expressing progenitors, others did not. Our study examines the expression and distribution of Myf-5 using immunohistochemical staining and western blotting of PRAT, gastrocnemius, and trapezius from goat at various developmental stages. Contrary to earlier beliefs, functionally divergent SkM gastrocnemius and trapezius showed similar Myf-5 expressional pattern. SkM abundantly expresses Myf-5 in developing myocytes which gradually becomes limited to the nucleus of myogenic stem cells and is retained only in a few differentiated postnatal fibers. During the same period, PRAT displays a unique brown-to-white transition. PRAT exhibited an elevated expression of Myf-5 during prenatal periods, which declines thereafter and becomes negligible during adulthood where it gets fully enriched white adipocytes. The reduction of Myf-5 during the neonatal period was common to all three tissues. However, Myf-5 expression was retained in some of the differentiated myofibers while it was undetectable in adult PRAT. These observations suggest a possible developmental interplay between adipose tissue and SkM where Myf-5 might be a major regulator.