Subcutaneous Adipose Tissue Research Articles

Transcriptomics of Subcutaneous Tissue of Lipedema Identified Differentially Expressed Genes Involved in Adipogenesis, Inflammation, and Pain.

Lipedema is a disease typically affecting women with a symmetrical, painful fat distribution disorder, which is hypothesized to be caused by impaired adipogenesis, inflammation, and extracellular matrix remodeling, leading to fibrosis and the development of edema in lipedema subcutaneous adipose tissue. The pathogenesis and molecular processes leading to lipedema have not yet been clarified. A whole transcriptome analysis of subcutaneous tissue of lipedema stages I (n = 12), II (n = 9), and III (n = 8) compared with hypertrophied subcutaneous tissue (n = 4) was performed. Further data about hormonal substitution and body morphology were collected. The study is registered at ClinicalTrials.gov (NCT05861583). We identified several differentially expressed genes involved in mechanisms leading to the development of lipedema. Some genes, such as PRKG2, MEDAG, CSF1R, BICC1, ERBB4, and ACP5, are involved in adipogenesis, regulating the development of mature adipocytes from mesenchymal stem cells. Other genes, such as MAFB, C1Q, C2, CD68, CD209, CD163, CD84, BCAT1, and TREM2, are predicted to be involved in lipid accumulation, hypertrophy, and the inflammation process. Further genes such as SHTN1, SCN7A, and SCL12A2 are predicted to be involved in the regulation and transmission of pain. In summary, the pathogenesis and development of lipedema might be caused by alterations in adipogenesis, inflammation, and extracellular matrix remodeling, leading to fibrosis and the formation of edema resulting in this painful disease. These processes differ from hypertrophied adipose tissue and may therefore play a main role in the formation of lipedema.

Non-invasive system delivering microwaves energy for localized adiposity reduction, skin laxity, and cellulite: Clinical evidence

Localized adiposities are the accumulation of subcutaneous adipose tissue resulting in an alteration of the body silhouette. This study evaluates the efficacy and safety of a non-invasive microwaves (MWs) device for the treatment of localized adiposities of the thighs and abdomen. Sixteen women enrolled underwent four sessions with the study device at intervals of 30 days. Clinical evaluation, anthropometric evaluation, ultrasound evaluations, and 3D photographs were performed. Cellulite and skin laxity were evaluated. Patients filled 4-points Global Aesthetic Improvement Scale (GAIS) and 10-points Visual Analog Scale. The mean abdominal circumference significantly (P <0.05) decreased 4 weeks after the last treatment, and the mean culotte/thighs circumference significantly (P < 0.05) decreased 4 weeks after the last treatment. Both cellulite and skin laxity were improved. The GAIS scores showed satisfactory results. No adverse effects were observed. This MWs system has been found to be safe and effective in the reduction of body circumferences.

Semaglutide modulates adipogenic differentiation and extracellular acidification in epicardial (EAT) and subcutaneous (SAT) adipose tissue stromal cells from patients with cardiovascular disease

Abstract Backround Cardiovascular disease (CVD) is the main cause of death in the world. One of the known risk factors is the epicardial fat (EAT) accumulation, which is around the myocardium and coronaries playing a paracrine role over them. Although mature and functional adipocytes are involved in energy balance and glucose metabolism, the hypertrophic state increases the production of fatty acid binding protein 4 (FABP4), which is a pro-inflammatory adipokine, with consequences on extracellular acidification. Recent data shows that glucagon-like peptide receptor agonists 1 (GLP1ra) drug improves the insulin response and reduces EAT thickness. Although GLP1ra has a direct effect on hypothalamus for reducing food intake, this drug might play a direct role on adipogenesis process in this fat stromal cells. Purpose Our study aims to demonstrate the effect of semaglutide on adipogenesis and metabolism in epicardial and subcutaneous stromal cells from patients with cardiovascular disease. Methods The study was approved by the Galician Research Ethics Committee, and subcutaneous adipose tissue (SAT) and EAT samples from 17 patients were obtained undergoing open-heart surgery with informed consent. Stromal cells from biopsies were isolated and cultured. Adipogenesis was induced for 15 days with or without 1 nM semaglutide, given by Novo-Nordisk (Bagsværd, Denmark), using an adipogenesis cocktail. Cells were lysed and RNA was isolated for RT-qPCR. Target genes were amplified for Glucagon like peptide 1- receptor (GLP1R), differentiation, adipogenesis, glucose metabolism and cellular markers. Extracellular acidification rate was measured with glycolytic rate assay on Seahorse. Lipids accumulation was tested by AdipoRed staining. Results Stromal cells from both tissues express GLP1R but higher differentiation factor (PGC1α) was detected in SAT compared to EAT (p=0.02), as well as adipogenesis induction. After semaglutide treatment, we observed a downregulation of FABP4 and GLUT1 in EAT (p=0.01 and p=0.02, respectively). Despite FABP4 was not modulated on SAT, there was a reduction of PGC1α levels. (p=0.02). Since glitazones upregulate PGC1α, which is used for adipogenesis induction, these results might suggest the counteract mechanism of semaglutide. The metabolism assay showed that semaglutide reduces extracellular acidification rate in EAT cells (p=0.04) and oxidative glycolysis with semaglutide treatment (p=0.003) but not in SAT cells. Conclusions Semaglutide reduces adipogenesis, through modulation of PGC1α transcription factor in EAT from patients with cardiovascular disease and extracellular acidification and oxidative glycolysis. These results might help to understand one of the mechanisms associated with EAT reduction in patients with semaglutide treatment.

Digoxin reduces senescence and restores dysfunctional endothelial-subcutaneous adipocyte cross-talk and dysregulated glucose homeostasis in patients with type 2 diabetes mellitus

Abstract Background Normal subcutaneous adipose tissue (SAT) function is dependent on SAT microvascular expansion. Heart failure with reduced ejection fraction (HF) and type 2 diabetes mellitus (DM) have a synergistic deleterious relationship and, of relevance to this, metabolic dysregulation may drive HF progression in DM. Chronic hyperinsulinemia is associated with adipocyte senescence, however any contributing role of SAT microvascular endothelial cell (SATMVEC) senescence on adverse microvascular expansion in type 2 diabetes mellitus (DM) remains unknown. Digoxin has been shown to have senolytic activity in murine cancer models. However, the potential therapeutic role of digoxin on SAT metabolic function is unexplored. Purpose We establish the presence of SATMVEC senescence and its effects on adipocyte function in people with HF and DM (HFDM). Moreover, we establish a therapeutic role for digoxin in targeting SATMVEC senescence, modulating SATMVEC-adipocyte crosstalk and restoring metabolic homeostasis. Methods We took pectoral SAT biopsies from 59 patients undergoing pacemaker implantation of whom 25 (42%) had HF and DM (HFDM). SATMVEC were isolated from SAT and were treated with 1ng/mL digoxin vs control for 24 hours before characterisation (cell function, expression of senescence-associated ß-galactosidase (ß-gal) and senescence associated secretory phenotype, SASP). Crosstalk between SATMVEC and subcutaneous white adipocytes were examined using co-culture techniques (Fig 1A). Paired digoxin vs control treated SATMVEC were seeded co-cultured with adipocytes for 24 hours, before adipocyte health was quantified, through 2-NBD-glucose uptake and expression of key adipogenic genes and proteins. Results Compared to HF alone, isolated SATMVEC from patients with HFDM had a senescent phenotype with increased SASP and ß-gal expression (p<0.05), reduced metabolic activity, ATP production, proliferative capacity, and impaired angiogenesis (p<0.05). In co-culture, SATMVEC from patients with HFDM had deleterious effects on adipocyte function: increasing expression of IL-6 (Fig 1C) and reducing 2-NBD-glucose uptake (p<0.05). Treatment of SATMVEC with digoxin reduced the SATMVEC senescent phenotype (Fig 1B) and increased 2-NBD-glucose adipocyte uptake (Figure 1D) (p<0.001). Conclusions SATMVEC from patients with HFDM have a senescent phenotype, and when in co-culture induce a proinflammatory adipocyte phenotype, resistant to glucose uptake. Digoxin reduces SATMVEC senescence, restores healthy adipocyte glucose homeostasis, and thus has the potential to repair dysfunctional SAT in patients with HFDM.

Impact of waist circumference and abdominal fat distribution on coronary artery disease severity stratified by computed tomography-derived SYNTAX score

Abstract Background Waist circumference (WC) is the most convenient anthropometric measure of obesity. Recently, abdominal fat distribution (AFD) has been identified as a more important risk factor for coronary artery disease (CAD) than the absolute amount of adipose tissue. However, studies examining the impact of body composition indicators (BCIs) on CAD severity are lacking. The computed tomography (CT)-derived SYNTAX score (CT-SXscore) is a feasible method for grading CAD severity based on coronary CT angiography (CTA) findings. Purpose This study was aimed to evaluate the association between BCI and CAD severity using the CT-SXscore. Methods We enrolled consecutive patients with suspected CAD who underwent CTA using a 320-row multidetector CT scanner between October 2014 and March 2020. Plain abdominal CT was also performed at the umbilical level to measure the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas. The total adipose tissue (TAT) area was calculated as the sum of VAT and SAT. To assess the AFD, the VAT/SAT (V/S) ratios were also calculated as the VAT area divided by the SAT area in each case. WC was measured by tracing the body contour at the umbilical level in CT images. The severity of coronary artery stenosis was assessed using CTA. Significant stenosis was defined as a stenosis diameter of ≥50%. The CT-SXscore was calculated in patients with more than one significant stenoses. Each stenotic lesion was evaluated to calculate the CT-SXscore in the same manner as the invasive coronary angiography assessment. We assessed the effects of BCI [i.e., WC, body mass index (BMI), each adipose tissue area, and V/S ratios] on the CT-SXscores. Results 308 eligible patients (mean age, 70.9 ± 10.6 years; 69.5% males) were evaluated. The median values of WC, BMI, TAT, SAT, VAT, and V/S ratio were 84.8 cm, 23.6 kg/m2, 198.2 cm2, 111.8 cm2, 81.0 cm2, and 0.67, respectively. Although WC showed a significant correlation with BMI, TAT, SAT, and VAT area, no correlation was observed between WC and V/S ratio (Figure1). The CT-SXscore showed no association with WC, BMI, and TAT area; however, it exhibited a weak negative correlation with the SAT area and a weak positive correlation with the VAT area. Additionally, a strong correlation was observed between the CT-SXscore and V/S ratio. In the multivariate regression analysis, WC, BMI, TAT, SAT, and VAT were no longer associated with the CT-SXscore after adjusting for traditional coronary risk factors, whereas the V/S ratio remained as the only independent predictor of CAD severity based on the CT-SXscore (Figure2). Conclusions WC was strongly correlated with other BCIs, except for the V/S ratio; however, it could not be identified as a predictive factor of CAD severity. Among the BCIs, only the V/S ratio was an independent predictor of CAD severity, indicating that the AFD revealed by the V/S ratio may be a more important risk factor for progression of CAD than other BCIs.Figure1Figure2

Human epicardial adipose tissue-derived factors promote atrial endothelial dysfunction: role of pro-inflammatory cytokines and AT1R/NADPH oxidases/SGLT2 pro-oxidant pathway

Abstract Introduction Epicardial adipose tissue (EAT) has been suggested to contribute to left atrium dysfunction via paracrine mechanisms to induce endothelial dysfunction, pro-arrhythmogenic and pro-remodeling responses thereby favoring atrial fibrillation (AF) onset. Recently, sodium-glucose co-transporter2 inhibitors (SGLT2i) have been shown to reduce AF incidence, EAT volume, differentiation and inflammation, however, the underlying mechanisms are unknown. Purpose This study investigates the impact of human EAT-derived mediators on atrial endothelial cell function and, if so, to characterize the role of SGLT2 using the inhibitor empagliflozin (EMPA). Methods Epicardial and subcutaneous adipose tissues (SAT) were collected from 70 cardiac patients at a university hospital. Conditioned medium (CM, 24 h) from fats were applied to porcine atrial endothelial cells (AECs, first passage) for 24 h. Histology of tissues was assessed by haematoxylin and eosin staining, protein expression by Western blot analysis or immunofluorescence staining, mRNA levels by RT-qPCR, formation of reactive oxygen species (ROS) and nitric oxide (NO) by fluorescent probes, and pro-inflammatory cytokine levels by ELISA. Results Compared to SAT, EATs were more vascularized with increased infiltration of M1-like macrophages, expression of proinflammatory cytokines (IL-1ß, IL-6, TNF-α), markers of ECs VCAM-1 and eNOS, fibrosis TGF-β, NADPH oxidases NOX-1 and SGLT1/2. These effects were associated with a pro-oxidant response that was inhibited by neutralizing Abs directed against IL-1ß or IL-6, and by inhibition of either NOS, NADPH oxidases, ACE, AT1R or SGLT2. Levels of SGLT2 and ROS in EATs were higher in AF compared to non-AF patients and progressively increasing with age. CM of EATs showed higher concentrations of IL-1ß, IL-6, TNF-α and MCP-1 than that of SAT. Exposure of AECs to CM of EATs increased the level of oxidative stress that was positively correlated to the level of pro-inflammatory cytokines, and reduced basal and bradykinin-induced NO formation that was prevented by EMPA. It also resulted in upregulation of p53 and SGLT2 expression, and nuclear translocation of NF-kB by CM of the top quartile inflamed EATs but not by the lowest quartile of EATs or SATs, prevented by EMPA. Conclusion The findings indicate that compared to SATs, the EATs showed higher in situ expression and release of pro-inflammatory cytokines that contributed to oxidative stress involving the AT1R/NADPH oxidases/SGLT2 pro-oxidant pathway. CMs of inflamed EATs induced AECs dysfunction, oxidative stress and activation of NF-kB involving pro-inflammatory cytokines and SGLT2. Thus, SGLT2i appear as an interesting strategy to decrease EAT inflammation and improve endothelial function contributing to prevent cardiac remodeling and fibrotic responses.

Metabolomic reprogramming of subcutaneous adipose tissue aggravates atherosclerosis via impaired adipocyte-macrophage crosstalk

Abstract Object: The bidirectional relationship between cardiometabolic syndrome and dysfunctional adipose tissue has received increasing attention. However, the metabolic alteration of subcutaneous adipose tissue during atherosclerosis has been overlooked. Methods In this study, we aimed to investigate the relationship between subcutaneous adipose tissue and atherosclerosis based on a combination strategy of single-cell sequencing and metabolomics in atherosclerotic mice and humans. Result Through our analysis of the clinical cohort with atherosclerosis, we discovered a correlation between the volume of subcutaneous adipose tissue and the characteristics of coronary plaques. Furthermore, by employing the snRNA-seq approach, we identified the metabolic landscape and cellular crosstalk within the subcutaneous adipose tissue of atherosclerotic mice. Lastly, through our analysis of the metabolic features in human adipose tissue, we successfully validated the Insulin-like Growth Factor 1 pathway as a crucial modulator in the adipocyte-macrophage crosstalk during the development of atherosclerosis. Conclusion The present study has provided further evidence that dysregulated metabolism of subcutaneous adipose tissue is involved in the development and progression of atherosclerosis, not only in humans but also in animal models.

Validation of fat mass metrics in pediatric obesity

Introduction Hudda-Index is a prediction model for fat mass (FM) based on simple anthropometric measures., FM is a crucial factor in the development of comorbidities, i.e., type 2 diabetes. Hence, Hudda-Index is a promising tool to facilitate identification of children at risk for metabolic comorbidities. It has been validated against deuterium dilution assessments, however, independent validation against the gold-standard for body composition analysis, magnetic resonance imaging (MRI), is lacking. The aim of this study is to validate FM calculated by Hudda-Index against FM measured by MRI. The secondary aim is to compare Hudda-Index to other anthropometric measures including body mass index (BMI), BMI-standard deviation score (BMI-SDS), waist/hip-ratio, waist circumference (WC) and skinfold thickness. Methods The study cohort consists of 115 individuals between the age of 9 and 15 years, recruited at Paracelsus Medical University Hospital in Salzburg (Austria) and Uppsala University Children's Hospital (Sweden). Anthropometry, blood samples, and oral glucose tolerance tests followed standard procedures. MRI examinations were performed to determine visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Results BMI and WC showed slightly stronger associations with the reference standard VAT (r=0.72 and 0.70, p<0.01, respectively) than Hudda-Index (r= 0.67, p<0.01). There is an almost perfect linear association between BMI and Hudda-Index. Accordingly, BMI and Hudda-Index both showed an acceptable association with cardiometabolic parameters. VAT was strongly associated with markers of liver status (LFF r=0.59, p<0.01) and insulin resistance (HOMA-IR r=0.71, p<0.01) and predicted metabolic dysfunction-associated steatotic liver disease (MASLD). Conclusion BMI, although an imperfect measure, remains the most reliable tool and estimates cardiometabolic risk more reliably than other anthropometry-based measures.

Fructose restriction has beneficial effects on adipose tissue distribution but not on serum adipokine levels: Post-hoc analysis of a double-blind randomized controlled trial.

We aimed to examine the effects of isocaloric fructose restriction on adipose tissue distribution and serum adipokines. Individuals with BMI >28 kg/m2 (n = 44) followed a 6-week fructose-restricted diet and were randomly allocated to (double-blind) oral supplementation with fructose (control) or glucose (intervention) powder three times daily. Visceral (VAT) and subcutaneous (SAT) adipose tissue was quantified with MRI. Serum interleukin 6 and 8, tumour necrosis factor alpha and adiponectin levels were measured with sandwich immunoassay. BMI decreased in both groups, but the change did not differ between groups (-0.1 kg/m2, 95%CI: -0.3; 0.5). SAT decreased statistically significantly in the control group (-23.2 cm3, 95%CI: -49.4; -4.1), but not in the intervention group. The change in SAT did not differ between groups (29.6 cm3, 95%CI: -1.2; 61.8). No significant differences in VAT were observed within or between study arms. The VAT/SAT ratio decreased statistically significantly in the intervention group (-0.02, 95%CI: -0.04; -0.003) and the change was significantly different between groups (-0.03, 95%CI: -0.54; -0.003). Serum adipokine levels were not affected by the intervention. This study shows that a fructose-restricted diet resulted in a favourable change in adipose tissue distribution, but did not affect serum adipokines. Further studies are warranted to clarify the underlying mechanisms how fructose affects adipose tissue distribution.

Weight Changes Are Linked to Adipose Tissue Genes in Overweight Women with Polycystic Ovary Syndrome.

Women with polycystic ovary syndrome (PCOS) have varying difficulties in achieving weight loss by lifestyle intervention, which may depend on adipose tissue metabolism. The objective was to study baseline subcutaneous adipose tissue gene expression as a prediction of weight loss by lifestyle intervention in obese/overweight women with PCOS. This is a secondary analysis of a randomized controlled trial where women with PCOS, aged 18-40 and body mass index (BMI) ≥ 27 were initially randomized to either a 4-month behavioral modification program or minimal intervention according to standard care. Baseline subcutaneous adipose tissue gene expression was related to weight change after the lifestyle intervention. A total of 55 obese/overweight women provided subcutaneous adipose samples at study entry. Weight loss was significant after behavioral modification (-2.2%, p = 0.0014), while there was no significant weight loss in the control group (-1.1%, p = 0.12). In microarray analysis of adipose samples, expression of 40 genes differed significantly between subgroups of those with the greatest weight loss or weight gain. 10 genes were involved in metabolic pathways including glutathione metabolism, gluconeogenesis, and pyruvate metabolism. Results were confirmed by real-time polymerase chain reaction (RT-PCR) in all 55 subjects. Expressions of GSTM5, ANLN, and H3C2 correlated with weight change (R = -0.41, p = 0.002; R = -0.31, p = 0.023 and R = -0.32, p = 0.016, respectively). GSTM5, involved in glutathione metabolism, was the strongest predictor of weight loss, and together with baseline waist-hip ratio (WHR) explained 31% of the variation in body weight change. This study shows that baseline subcutaneous adipose tissue genes play a role for body weight outcome in response to lifestyle intervention in overweight/obese women with PCOS.

Analysis of Physiological Oxygen Concentrations in Different Abdominal Fat Layers by Body Mass Index.

Physiological oxygen concentration in adipose tissue is closely linked to metabolic disorders such as chronic inflammation and insulin resistance. However, the nature of the variation in the oxygen levels of adipose tissue with body mass index (BMI) and depths of abdominal fat remain unclear. Therefore, this study aimed to elucidate the patterns of oxygen concentration in adipose tissue layers according to BMI. In this study, patients undergoing abdominal fat removal surgery were divided into the normal-weight (NW) or overweight-obese (OW) groups based on their BMI. Oxygen concentrations in abdominal superficial (sSAT) and deep subcutaneous adipose tissue (dSAT) were measured. The oxygen consumption rate, mean cell area, and capillary density in both tissue layers were compared between the two groups. Furthermore, the interaction between these three variables, BMI, and adipose tissue oxygen concentration, was analyzed using linear regression. A total of 42 patients were recruited in this study and we observed that oxygen concentration in the sSAT was significantly lower than in the dSAT, irrespective of BMI. In terms of the oxygen concentration in the dSAT, OW's was significantly lower than that of NW's. Linear regression analysis revealed a significant correlation between dSAT oxygen concentration and BMI, mean adipocyte area, and vascular density. Individuals who are obese have significantly lower oxygen levels in the deep abdominal adipose tissue, and this is influenced by BMI, adipocyte area, and capillary density. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Two Regions with Different Expression of Lipogenic Enzymes in Rats' Posterior Subcutaneous Fat Depot.

Lipid metabolism in various adipose tissue depots can differ vastly. This also applies to lipogenesis, the process of synthesizing fatty acids from acetyl-CoA. This study compared the expression of some lipogenic enzymes: fatty acid synthase (FASN), ATP-citrate lyase (ACLY), and malic enzyme 1 (ME1) in different regions of the posterior subcutaneous adipose tissue in rats. Methods and Results: Posterior subcutaneous adipose tissue collected from twelve-month-old Wistar rats was divided into six parts (A-F). The expression of genes encoding lipogenic enzymes was assessed by measuring their activity and mRNA levels using real-time PCR. In the gluteal region of the fat pad, there were much higher levels of activity and mRNA for these lipogenic enzymes compared to the dorsolumbar region. The mRNA level of FASN increased by more than twentyfold, whereas the level of ME1 and ACLY increased eight- and fivefold respectively. This phenomenon was observed in both old and young animals. Furthermore, the lack of uncoupling protein one (Ucp1) expression suggests that neither the presence of brown adipocytes in the gluteal part nor the transformation of white adipocytes into beige contributed to the observed differences. Conclusion: These results indicate that the gluteal white adipose tissue appears to be a unique and separate subcutaneous fat depot.

Cellular Characteristics and Protein Signatures of Human Adipose Tissues from Donors With or Without Advanced Coronary Artery Disease

Background/Objectives: Perivascular adipose tissue (PVAT) exerts a paracrine effect on blood vessels and our objective was to understand PVAT molecular signatures related to cardiovascular disease. Methods: We studied two groups: those undergoing mitral valve repair/replacement (VR, n = 16) and coronary artery bypass graft (CABG, n = 38). VR donors did not have coronary artery disease, whereas CABG donors had advanced coronary artery disease. Clinical and tissue pathologies and proteomics from adipose tissue were assessed. Results: Donors undergoing VR had a lower body mass index (p = 0.01), HbA1C (p = 0.0023), and incidence of diabetes (p = 0.022) compared to CABG. VR donors were overall healthier, with higher cardiac function compared to CABG donors, based on ejection fraction. Although adipose histopathology between groups was not markedly different, PVAT had smaller and more adipocytes compared to subcutaneous adipose tissues. These differences were validated by whole specimen automated morphological analysis, and anisotropy analysis showed small (2.8–7.5 μm) and large (22.8–64.4 μm) scale differences between perivascular and subcutaneous adipose tissue from CABG donors, and small scale changes (2.8–7.5 μm) between perivascular and subcutaneous adipose tissue from VR donors. Distinct protein signatures in PVAT and subcutaneous adipose tissue include those involved in secretion, exosomes and vesicles, insulin resistance, and adipocyte identity. Comparing PVAT and subcutaneous adipose tissue from CABG donors, there were 82 significantly different proteins identified with log fold change ≥ 0.3 or ≤−0.3 (p < 0.05). Using this threshold, there were 36 differences when comparing PVAT and subcutaneous adipose tissue from VR donors, 58 differences when comparing PVAT from CABG or VR donors, and 55 when comparing subcutaneous adipose tissue from CABG vs. VR donors. Conclusions: Routine histopathology cannot differentiate between PVAT from donors with or without coronary artery disease, but multiscale anisotropy analysis discriminated between these populations. Our mass spectrometry analysis identified a cohort of proteins that distinguish between adipose depots, and are also associated with the presence or absence of coronary artery disease.

Exploring the Impact of Resistance Training at Moderate Altitude on Metabolic Cytokines in Humans: Implications for Adipose Tissue Dynamics.

Hypobaric hypoxia (HH) limits oxygen supply to tissues and increases metabolic demands, especially during exercise. We studied the influence of HH exposure on the subcutaneous adipose tissue (SAT) thickness and circulating metabolic-related cytokines levels after a resistance training (RT) program. Twenty trained men participated in a traditional hypertrophy RT for 8 weeks (three sessions/week) under intermittent terrestrial HH (2320 m) or normoxia (N, 690 m) conditions. Before, at week 6, and after the RT, SAT, and vastus lateralis (VL) muscle thickness were measured by ultrasound. Blood samples were taken to analyse serum cytokines (IL-6, IL-15, irisin, and myostatin) by multiplex immunoassay. Our findings revealed a moderate reduction in IL-6 and irisin in HH following the RT (ES < -0.64; p < 0.05). Additionally, RT in HH promoted serum IL-15 release (ES = 0.890; p = 0.062), which exhibited a trivial inverse association with the reductions observed on SAT (-17.69%; p < 0.001) compared with N. RT in HH explained ~50% of SAT variance (p < 0.001). These results highlight the benefit of stressor factors linked to RT in HH on SAT through the modulation of serum metabolic cytokine profiles, suggesting a potential effect on overall body composition.

Mendelian randomization and multi-omics approach analyses reveal impaired glucose metabolism and oxidative phosphorylation in visceral adipose tissue of women with polycystic ovary syndrome.

What is the significance of visceral adipose tissue (VAT) in the pathogenesis of polycystic ovary syndrome (PCOS) and its impact on the regulation of metabolic disorders in women with PCOS? We revealed a potentially causal relationship between increased genetically predicted VAT and PCOS-related traits, and found that VAT exhibited impaired glucose metabolism and mitochondrial oxidative phosphorylation (OXPHOS) in women with PCOS. PCOS is a common reproductive endocrine disorder accompanied by many metabolic abnormalities. Adipose tissue is a metabolically active endocrine organ that regulates multiple physiological processes, and VAT has a much stronger association with metabolism than subcutaneous adipose tissue does. Mendelian randomization (MR) analysis was used to investigate the potential causal association between genetically predicted VAT and the risk of PCOS. Data for MR analysis were extracted from European population cohorts. VAT samples from sixteen PCOS patients and eight control women who underwent laparoscopic surgery were collected for proteomics and targeted metabolomics analyses. PCOS was diagnosed according to the 2003 Rotterdam Criteria. The control subjects were women who underwent laparoscopic investigation for infertility or benign indications. Proteomics was performed by TMT labeling and liquid chromatography-tandem mass spectrometry analysis, and targeted metabolomics was performed by ultra-performance liquid chromatography-tandem mass spectrometry analysis. The key differentially expressed proteins (DEPs) were validated by immunoblotting. MR analysis revealed a potentially causal relationship between increased genetically predicted VAT and PCOS, as well as related traits, such as polycystic ovaries, total testosterone, bioavailable testosterone, and anti-Müllerian hormone, while a negative relationship was found with sex hormone-binding globulin. Enrichment pathway analysis of DEPs indicated the inhibition of glycolysis and activation of mitochondrial OXPHOS in the VAT of PCOS patients. MR analysis revealed that key DEPs involved in glycolysis and OXPHOS were significantly linked to PCOS and its related traits. Dot blot assay confirmed a significant decrease in glycolysis enzymes PKM2 and HK1, and an increase in mitochondrial Complex I and III subunits, NDUFS3 and UQCR10. Moreover, metabolomics analysis confirmed down-regulated metabolites of energy metabolic pathways, in particular glycolysis. Further analysis of PCOS and control subjects of normal weight revealed that dysregulation of glucose metabolism and OXPHOS in VAT of women with PCOS was independent of obesity. The mass spectrometry proteomics data have been deposited to the iProX database (http://www.iprox.org) with the iProX accession: IPX0005774001. There may be an overlap in some exposure and outcome data, which might affect the results in the MR analysis. The changes in protein expression of key enzymes affect their activities and disrupt the energy metabolic homeostasis in VAT, providing valuable insight for identifying potential intervention targets of PCOS. This work was supported by the National Key Research and Development Project of China (2021YFC2700402), the National Natural Science Foundation of China (82071608, 82271665), the Key Clinical Projects of Peking University Third Hospital (BYSY2022043), and the CAMS Innovation Fund for Medical Sciences (2019-I2M-5-001). All authors report no conflict of interest. N/A.

Associations of Urinary Cadmium with Body Composition and Fat Distribution in US Adults: Findings from NHANES 2011-2018.

The effects of cadmium (Cd) on metabolic physiology remain controversial. Given the varying metabolic impacts associated with different body compositions, investigating the relationship between Cd exposure and body composition may facilitate further research. Here, the associations of body composition and fat distribution with urine Cd (UCd) were evaluated. This analysis included 2979 adult participants from the 2011-2018 National Health and Demographic Survey (NHANES). UCd was measured using inductively coupled plasma mass spectrometry and adjusted for urinary creatinine. Body composition and fat distribution were estimated using dual-energy x-ray absorptiometry (DXA). The study results show that UCd was negatively associated with fat mass index (FMI) and percent fat mass (p for trend < 0.001), and the negative correlation between UCd and FMI was stronger in males and smokers (all p for interaction < 0.05). In terms of abdominal fat distribution, UCd was negatively associated with abdominal subcutaneous adipose tissue (SAT) mass (p for trend < 0.001), but with abdominal visceral adipose tissue (VAT) mass only in those with low percent fat mass (< 32.3%) (p for trend = 0.026 and p for interaction < 0.05). UCd was positively related to percent VAT (p for trend < 0.001) and visceral-to-subcutaneous (VAT/SAT) ratio (p for trend = 0.003). And there was a significant negative association between UCd and android-to-gynoid (A/G) ratio (p for trend = 0.001). Meanwhile, UCd was negatively correlated with fat-free mass index (FFMI) (p for trend < 0.001). And the negative correlation between UCd and FFMI was stronger in males, smokers, and individuals with < 32.3 percent fat mass (all p for interaction < 0.05). We found the association of UCd with body composition and fat distribution, with distinct patterns observed in different demographic groups. These findings underscore the importance of considering UCd exposure in the context of body composition and fat distribution.

Postnatal surge of adipose-secreted leptin is a robust predictor of fat mass trajectory in mice.

The transient postnatal increase in circulating leptin levels, known as leptin surge, may increase later susceptibility to diet-induced obesity in rodents. However, the source of leptin during the surge needs to be better characterized, and the long-term effects of leptin are contradictory. Characterization of the interaction of leptin with the genetic background, sex, and other factors is required. Here, we focused on the impact of circulating leptin levels and several related variables, measured in 2- and 4-week-old (i) obesity-prone C57BL/6 (B6) and (ii) obesity-resistant A/J mice. In total, 264 mice of both sexes were used. Posttranscriptionally controlled leptin secretion from subcutaneous white adipose tissue, the largest adipose tissue depot in mice pups, was the primary determinant of plasma leptin levels. When the animals were randomly assigned standard chow or high-fat diet (HFD) between 12 - 24 weeks of age, the obesogenic effect of HFD-feeding was observed in B6 but not A/J mice. Only leptin levels at 2 weeks, i.e., close to the maximum in the postnatal leptin surge, correlated with both body weight (BW) trajectory throughout the life and adiposity of the 24-week-old mice. Leptin surge explained 13 and 7 % of the variance in BW and adiposity of B6 mice and 9 and 35 % of the variance in these parameters in A/J mice, with a minor role of sex. Our results prove the positive correlation between the leptin surge and adiposity in adulthood, reflecting the fundamental biological role of leptin. This role could be compromised in obese subjects.

Chemotherapy effects on mitochondrial function in adipose tissue in oesophageal and gastroesophageal junction adenocarcinomas with or without associated cachexia: protocol for a prospective, comparative observational study (ChiFMeOE)

IntroductionCachexia is strongly associated with digestive cancers, particularly oesogastric cancer. Mitochondria in adipose tissue are involved in the regulation of metabolism and physiopathology of cancer cachexia in animal studies. Chemotherapeutic...

Native corn (Zea mays L., cv. ‘Elotes Occidentales’) polyphenols extract reduced total cholesterol and triglycerides levels, and decreased lipid accumulation in mice fed a high-fat diet

Obesity is a complex disease with numerous molecular and metabolic implications that could be prevented through proper diet and lifestyle. Native corn is a promissory underutilized plant species containing bioactive compounds that could reduce the impact of obesity. This research aimed to characterize and evaluate the anti-obesogenic effect of a polyphenols-rich extract of native corn (‘Elotes Occidentales’) in HFD-fed mice. The powdered extract was administered using gelatins to C57BL/6 J mice randomly divided into four groups (n:8/group) for 13 weeks: standard diet (SD) group, HFD group, HFD+200 mg extract/kg body weight (BW), and HFD+400 mg extract/kg BW/day. Ellagic acid, chlorogenic acid, rutin, and kaempferol were the most abundant phenolics (2022.44–4028.43 µg/g). Among the HFD groups, the highest dose of the extracts promoted the lowest BW gain, and fasting triglycerides and cholesterol levels. Moreover, the HFD+400 mg/kg BW group showed the lowest epididymal and subcutaneous adipose tissue weight and adipocytes’ diameter and area between the HFD-treated animals. The extract administration prevented hepatic lipid accumulation. Rutin demonstrated the highest in silico binding affinity with proteins from the AMPK pathway (ACACA, SIRT1, and SREBP1) (-6.70 to −8.70 kcal/mol). Results indicated beneficial effects in alleviating obesity-associated parameters in vivo due to bioactive compounds from native maize extracts.

Association Between Body Composition Measured by Artificial Intelligence and Long-Term Sequelae After Acute Pancreatitis.

The clinical utility of body composition in the development of complications of acute pancreatitis (AP) remains unclear. We aimed to describe the associations between body composition and the recurrence of AP. We performed a retrospective study of patients hospitalized with AP at three tertiary care centers. Patients with computer tomography (CT) imaging of the abdomen at admission were included. A previously validated and fully automated abdominal segmentation algorithm was used for body composition analysis. Hospitalization for a recurrent episode of AP was the primary endpoint. Secondary endpoints included the development of chronic pancreatitis (CP) or diabetes mellitus (DM) in patients who were evaluated. Cox Proportional Hazards regression was used. From a total of 347 patients, 89 (25.6%) were hospitalized for recurrent AP (median time: 219days). Thirty-four of 112 patients (30.4%) developed CP (median time: 311days) and 22 of 88 (25.0%) developed DM (median time: 1104days). After adjusting for age, male sex, first episode of AP, BUN, and severity of AP, we found that obesity, body mass index, alcohol pancreatitis, and gallstone pancreatitis were significantly associated with a recurrent episode of AP. Body composition was not associated with recurrent AP. In unadjusted analysis, subcutaneous adipose tissue (SAT) (HR 0.87 per 10 cm2, p = 0.002) was associated with CP. Skeletal muscle (SM) mass approached significance for CP (p = 0.0546). Intermuscular adipose tissue (IMAT) (HR 1.45 per 5 cm2, p = 0.0264) was associated with DM. Body composition was not associated with having a recurrent AP. At follow-up, 30% and 25% of evaluated patients developed CP and DM, respectively. A higher SAT and IMAT were associated with a lower incidence of CP and higher incidence of DM, respectively.