Visceral Adipose Tissue Research Articles

Evaluation of Change in Body Composition, including Phase Angle, in Post-Myocardial Infarction Patients Rehabilitated under the KOS-Zawał (MC-AMI) Programme.

Background: Ischaemic heart disease, including myocardial infarction, is one of the main causes leading to heart failure as a consequence of ischaemic myocardial damage. In recent years, survival in the acute phase of myocardial infarction has improved significantly, but the high mortality rate within 12 months of hospital discharge (reaching up to 9.8% in Poland) remains a challenge. Therefore, the KOS-Zawał (MC-AMI) comprehensive 12-month post-MI care programme was introduced in Poland in 2017. Aim: This study aimed to assess body composition (including, but not limited to, the phase angle, visceral fat, total body fat, redistribution between intracellular and extracellular fluid in the body, and metabolic age) using a bioelectrical impedance analysis (BIA) in post-MI patients before and after early post-MI rehabilitation who were participating in the KOS-Zawał (MC-AMI) programme. Methods: This study involved an examination (before rehabilitation) of 94 post-myocardial infarction patients who were referred to a cardiology appointment within 7-10 days of hospital discharge, during which a clinical assessment, electrocardiogram, and biochemical blood tests (complete blood count, CRP, and serum creatinine) were performed. For various reasons (death, qualification for device implantation, non-completion of rehabilitation, failure to attend a follow-up BIA), data from 55 patients who were examined twice (before and after rehabilitation) were used for the final analysis. Measurements were taken using a high-grade Tanita MC-780 BIA body composition analyser, which measured the resistance of tissues to a low-intensity electrical impulse (not perceptible to the subject). Results: Participation in rehabilitation as part of the KOS-Zawał (MC-AMI) programme was associated with a decrease in metabolic age in patients, with a reduction in visceral fat levels and levels of adipose tissue in the lower and upper limbs. Moreover, a clinically beneficial reduction in the ratio of extracellular water to total body water was also observed. These changes were statistically significant (p < 0.005). In contrast, there were no statistically significant differences in the change in phase angle values in the subjects before and after the 5-week post-infarction rehabilitation. Conclusions: Participation in early post-myocardial infarction rehabilitation as part of the KOS-Zawał (MC-AMI) programme (25 training sessions) is associated with significant improvements in body composition parameters, such as visceral adipose tissue, limb fat, and water redistribution, and, consequently, a reduction in metabolic age, despite no significant increase in phase angle values. It was hypothesised that the good baseline condition of the subjects might explain the lack of significant change in the phase angle over the short observation period. For further analysis, it would be worthwhile to increase the number of patients with baseline reduced phase angle values and monitor changes in this parameter throughout rehabilitation and the entire MC-AMI programme, because changes in the phase angle may also be influenced by other programme components such as dietary or psychological education. It is worth considering implementing a regular BIA assessment in patients in the programme as a motivating stimulus for diligent exercise and extending rehabilitation to be followed by telerehabilitation or hybrid telerehabilitation.

Passive mechanical properties of adipose tissue and skeletal muscle from C57BL/6J mice

Skeletal muscle and adipose tissue are characterized by unique structural features finely tuned to meet specific functional demands. In this study, we investigated the passive mechanical properties of soleus (SOL), extensor digitorum longus (EDL) and diaphragm (DIA) muscles, as well as subcutaneous (SAT), visceral (VAT) and brown (BAT) adipose tissues from 13 C57BL/6J mice. Thereto, alongside stress-relaxation assessments we subjected isolated muscles and adipose tissues (ATs) to force-extension tests up to 10% and 30% of their optimal length, respectively. Peak passive stress was highest in the DIA, followed by the SOL and lowest in the EDL (p < 0.05). SOL displayed also the highest Young's modulus and hysteresis among muscles (p < 0.05). BAT demonstrated highest peak passive stress and Young's modulus followed by VAT (p < 0.05), while SAT showed the highest hysteresis (p < 0.05). When comparing data across all six biological specimens at fixed passive force intervals (i.e., 20–40 and 50–70 mN), skeletal muscles exhibited significantly higher peak stresses and strains than ATs (p < 0.05). Young's modulus was higher in skeletal muscles than in ATs (p < 0.05). Muscle specimens exhibited slower force relaxation in the first phase compared to ATs (p < 0.05), while there was no significant difference in behavior between muscles and AT in the second phase of relaxation. The study revealed distinctive mechanical behaviors specific to different tissues, and even between different muscles and ATs. These variations in mechanical properties are likely such to optimize the specific functions performed by each biological tissue.

Fat-associated lymphoid clusters: Supporting visceral adipose tissue B cell function in immunity and metabolism.

It is now widely understood that visceral adipose tissue (VAT) is a highly active and dynamic organ, with many functions beyond lipid accumulation and storage. In this review, we discuss the immunological role of this tissue, underpinned by the presence of fat-associated lymphoid clusters (FALCs). FALC's distinctive structure and stromal cell composition support a very different immune cell mix to that found in classical secondary lymphoid organs, which underlies their unique functions of filtration, surveillance, innate-like immune responses, and adaptive immunity within the serous cavities. FALCs are important B cell hubs providing B1 cell-mediated frontline protection against infection and supporting B2 cell-adaptative immune responses. Beyond these beneficial immune responses orchestrated by FALCs, immune cells within VAT play important homeostatic role. Dysregulation of immune cells during obesity and aging leads to chronic pathological "metabolic inflammation", which contributes to the development of cardiometabolic diseases. Here, we examine the emerging and complex functions of B cells in VAT homeostasis and the metabolic complications of obesity, highlighting the potential role that FALCs play and emphasize the areas where further research is needed.

Are Young People with Turner Syndrome Who Have Undergone Treatment with Growth and Sex Hormones at Higher Risk of Metabolic Syndrome and Its Complications?

Metabolic syndrome (MetS), characterized by visceral obesity, glucose abnormalities, hypertension and dyslipidemia, poses a significant risk of diabetes and cardiovascular disease. Turner syndrome (TS), resulting from X chromosome abnormalities, carries health complications. Despite growing evidence of an increased risk of MetS in women with TS, its prevalence and risk factors remain under investigation. These considerations are further complicated by the varying timing and dosages of treatment with growth hormone and sex hormones. We conducted a cross-sectional study comparing 44 individuals with TS with 52 age-matched control subjects. Growth hormone treatment in the study group was administered for varying lengths of time, depending on clinical response. We collected anthropometric, metabolic, endocrine and body composition data. Statistical analyses included logistic regression. Baseline characteristics, including age, BMI and height, were comparable between the TS and control groups. Hormonally, individuals with TS showed lower levels of testosterone, DHEA-S, and cortisol, as well as elevated FSH. Lipid profiles indicated an atherogenic profile, and the body composition analysis showed increased visceral adipose tissue in those with TS. Other metabolic abnormalities were common in individuals with TS too, including hypertension and impaired fasting glucose levels. The risk of MetS components was assessed in subgroups according to karyotypes: monosomy 45X0 vs. other mosaic karyotypes. Logistic regression analysis showed a significant association between increased visceral adipose tissue in subjects with TS. Those with metabolic complications tended to have less muscle strength compared to those without these complications in both the study and control groups. This study highlights the unique metabolic and cardiovascular risk profile of individuals with TS, characterized by atherogenic lipids, higher levels of visceral adipose tissue and increased metabolic abnormalities. These findings underscore the importance of monitoring metabolic health in individuals with TS, regardless of age, BMI or karyotype, and suggest the potential benefits of lifestyle modification, building more muscle strength, and weight control strategies. Further research is needed to better understand and address the metabolic challenges faced by women with TS.

Deep learning imaging phenotype can classify metabolic syndrome and is predictive of cardiometabolic disorders

BackgroundCardiometabolic disorders pose significant health risks globally. Metabolic syndrome, characterized by a cluster of potentially reversible metabolic abnormalities, is a known risk factor for these disorders. Early detection and intervention for individuals with metabolic abnormalities can help mitigate the risk of developing more serious cardiometabolic conditions. This study aimed to develop an image-derived phenotype (IDP) for metabolic abnormality from unenhanced abdominal computed tomography (CT) scans using deep learning. We used this IDP to classify individuals with metabolic syndrome and predict future occurrence of cardiometabolic disorders.MethodsA multi-stage deep learning approach was used to extract the IDP from the liver region of unenhanced abdominal CT scans. In a cohort of over 2,000 individuals the IDP was used to classify individuals with metabolic syndrome. In a subset of over 1,300 individuals, the IDP was used to predict future occurrence of hypertension, type II diabetes, and fatty liver disease.ResultsFor metabolic syndrome (MetS) classification, we compared the performance of the proposed IDP to liver attenuation and visceral adipose tissue area (VAT). The proposed IDP showed the strongest performance (AUC 0.82) compared to attenuation (AUC 0.70) and VAT (AUC 0.80). For disease prediction, we compared the performance of the IDP to baseline MetS diagnosis. The models including the IDP outperformed MetS for type II diabetes (AUCs 0.91 and 0.90) and fatty liver disease (AUCs 0.67 and 0.62) prediction and performed comparably for hypertension prediction (AUCs of 0.77).ConclusionsThis study demonstrated the superior performance of a deep learning IDP compared to traditional radiomic features to classify individuals with metabolic syndrome. Additionally, the IDP outperformed the clinical definition of metabolic syndrome in predicting future morbidities. Our findings underscore the utility of data-driven imaging phenotypes as valuable tools in the assessment and management of metabolic syndrome and cardiometabolic disorders.

The Role of microRNA in the Regulation of Cortisol Metabolism in the Adipose Tissue in the Course of Obesity.

The similarity of the clinical picture of metabolic syndrome and hypercortisolemia supports the hypothesis that obesity may be associated with impaired expression of genes related to cortisol action and metabolism in adipose tissue. The expression of genes encoding the glucocorticoid receptor alpha (GR), cortisol metabolizing enzymes (HSD11B1, HSD11B2, H6PDH), and adipokines, as well as selected microRNAs, was measured by real-time PCR in adipose tissue from 75 patients with obesity, 19 patients following metabolic surgery, and 25 normal-weight subjects. Cortisol levels were analyzed by LC-MS/MS in 30 pairs of tissues. The mRNA levels of all genes studied were significantly (p < 0.05) decreased in the visceral adipose tissue (VAT) of patients with obesity and normalized by weight loss. In the subcutaneous adipose tissue (SAT), GR and HSD11B2 were affected by this phenomenon. Negative correlations were observed between the mRNA levels of the investigated genes and selected miRNAs (hsa-miR-142-3p, hsa-miR-561, and hsa-miR-579). However, the observed changes did not translate into differences in tissue cortisol concentrations, although levels of this hormone in the SAT of patients with obesity correlated negatively with mRNA levels for adiponectin. In conclusion, although the expression of genes related to cortisol action and metabolism in adipose tissue is altered in obesity and miRNAs may be involved in this process, these changes do not affect tissue cortisol concentrations.

Effect of contrast phase on quantitative analysis of skeletal muscle and adipose tissue by computed tomography

ObjectivesSignificant variability exists in the contrast phases applied during computed tomography (CT) studies when assessing morphometric measurements of muscle area (CT-assessed sarcopenia) and density (CT-assessed myosteatosis) and visceral adipose tissue area (CT-assessed visceral obesity). This study explored the impact of contrast phase timing on changes in morphometric measurements of body composition. MethodsThis single-center retrospective cohort study included 459 patients undergoing a multiphase CT scan. Morphometric measurements were obtained at the third lumbar vertebra level. Patients were classified as sarcopenic, myosteatotic, or visceral obese using predefined cutoff values. The intraclass correlation coefficient was used to assess correlations across different enhancement phases, and Cohen's κ measured the inter-enhancement agreement for sarcopenia, myosteatosis, and visceral obesity. ResultsSignificant differences were observed in mean visceral adipose tissue area, muscle density, and muscle area (P < 0.001). The intraclass correlation coefficient between unenhanced and arterial phases was 0.987 (95% confidence interval [CI], 0.759–0.996) for adipose tissue, 0.995 (95% CI, 0.989–0.997) for muscle area, and 0.850 (95% CI, 0.000–0.956) for muscle density. However, when morphometric measurements were categorized using predefined cutoffs, the κ agreement was considerably lower, particularly for CT-assessed myosteatosis, ranging from 0.635 (unenhanced to arterial) to 0.331 (unenhanced to late venous phase). ConclusionsDifferent CT contrast phases induce small but clinically significant alterations in the measurements of muscle area and density and visceral fat. Such minor changes can result in misclassification issues when fixed cutoff values are used to diagnose myosteatosis with CT. This underscores the importance of reporting absolute values and the specific contrast phase used in future studies.

Adipose Triglyceride Lipase–Mediated Adipocyte Lipolysis Exacerbates Acute Pancreatitis Severity in Mouse Models and Patients

Dyslipolysis of adipocytes has played a critical role in various diseases. Adipose triglyceride lipase (ATGL) is a rate-limiting enzyme in adipocyte autonomous lipolysis. However, whether the degree of adipocyte lipolysis relates to the prognoses in acute pancreatitis (AP) and the role of ATGL mediated lipolysis in the pathogenesis of AP remains elusive. The visceral adipose tissue (VAT) consumption rate (VATR) in the acute stage was measured in both AP patients and mouse models. Lipolysis levels and ATGL expression were detected in caerulein (CER)-induced AP models. CL316,243, a lipolysis stimulator, and adipose tissue-specific ATGL knockout (AAKO) mice were used to further investigate the role of lipolysis in AP. The ATGL-specific inhibitor, Atglistatin, was performed in C57Bl/6N and ob/ob AP models. This study found that increased VATR in the acute phase was independently associated with adverse prognoses in AP patients, which was validated in mice AP models. Lipolysis of adipocytes was elevated in AP mice. Stimulation of lipolysis could aggravate AP. Genetic blockage of ATGL specifically in adipocytes was able to alleviate the damage to AP. The application of Atglistatin could effectively protect against AP in both lean and obese mice. These findings demonstrated that ATGL-mediated adipocyte lipolysis exacerbates AP and highlighted the therapeutic potential of ATGL as a drug target for AP.

Effects of N-acetylcysteine on the expressions of UCP1 and factors related to thyroid function in visceral adipose tissue of obese adults: a randomized, double-blind clinical trial

BackgroundEvidences have shown that obesity is influenced by various factors, including various hormones such as thyroid hormones and the body’s metabolism rate. It seems that practical solutions such as weight loss diets and common drugs can affect these potential disorders. In this study, we investigate one of these common drugs, N-Acetylcysteine (NAC), on expressions of UCP1 and factors related to thyroid function in adults with obesity.Methods and analysisThe current investigation was carried out as a randomized clinical trial (RCT) including 43 adults with obesity who were potential candidates for bariatric surgery. These individuals were randomly divided into two groups: 600 mg of NAC (n = 22) or placebo (n = 21) for a duration of 8 weeks. Visceral adipose tissue was utilized in the context of bariatric surgery to investigate the gene expression of UCP1 and thyroid function. Polymerase chain reaction (PCR) was performed in duplicate for UCP1, DIO2, DIO3, THRα and β, and 18s RNA (as an internal control) using the provided instructions to investigate the expression of the respective genes.ResultsOur findings revealed that after 8 weeks compared to placebo, NAC caused a significant decrease in the expression of the DIO3 gene as one of the genes related to thyroid function and metabolism. However, regarding other related genes, no statistically significant was found (despite the increase in UCP1, DIO2, and THRα expression and decrease in THRβ expression). In addition, after adjustment of possible confounders, no significant effect was observed on anthropometric factors and serum levels of thyroid hormones.ConclusionThe results of this study indicate that, following an 8-week period, NAC effectively decreases the expression of the DIO3 gene in the visceral fat tissue, in comparison to the placebo.

Association between visceral adipose tissue area and infertility: a cross-sectional analysis

Research Question: The effect of obesity on fertility has been studied in recent years. However, the direct relationship between intra-abdominal fat obesity and female reproductive health remains inconclusive.Design: The study analysis data from the 2013-2018 National Health and Nutrition Examination Survey, with a total of 3013 women were enrolled. The participants were divided into an “infertility” group and a “non-infertility” group. Differences between two groups were analyzed using a weighted Student's t-test or Mann-Whitney U test for continuous variables or a weighted Chi-squared test for categorical data. Visceral adipose tissue area (VATA) is assessed by dual-energy X-ray absorptiometry. The independent association between infertility and log VATA was assessed by weighted multivariate logistic regression models. Subgroup analyses were performed to assess the strength of the results. Interaction tests were used to examine whether covariates interacted with log VATA to influence infertility.Results: The results showed that log VATA was significantly higher in the infertility group than in the non-infertility group. After adjustment for potential confounders, the results of multivariate logistic regression analysis revealed that an increase in log VATA was associated with a growing prevalence of female infertility (OR=2.453, 95% CI: 1.278-4.792). Subgroup analyses showed this association was still consistent in individuals under 35 years old (P=0.002), Mexican-American (P=0.033), non-hypertensive (P=0.013), and non-diabetic individuals (P=0.003).Conclusions: This study showed that enlarged VATA was associated with an increased risk of infertility. The direct effect of VATA on female infertility needs to be further clarified to provide a basis for future prevention and treatment of female infertility.

Abstract PO1-11-09: Body composition correlates with BMI and menopausal status in patients with breast cancer

Abstract Background: Obesity is associated with higher risk of breast cancer (BC)-related death, all-cause mortality, and recurrence. While used to estimate body fat, body mass index (BMI) is insensitive to body fat distribution and lean muscle mass. We hypothesized that BMI categories (BMI 18.5-24.9 [healthy], 25-29.9 [overweight], and ≥30 kg/m2 [obesity]) would not correlate with CT-derived body composition. Methods: We retrospectively identified 180 patients diagnosed with new or recurrent Stage I-IV BC who presented to Johns Hopkins from 2015-2018 and were part of an institutional database. We extracted demographics, diagnosis date, cancer characteristics, BMI, and CT abdomen pelvis scans from the medical record. Baseline BMI was defined as the closest measurement to diagnosis between 1 year prior and 1 month after diagnosis. Baseline CT was within 6 months of and closest to the baseline BMI date. Fully automated deep-learning algorithms identified L1 and performed muscle and adipose tissue segmentation and quantification. Body composition data included: cross-sectional areas (CSA) of subcutaneous, visceral, and total adipose tissue; the mean, median, and standard deviation of the average of the muscle attenuation (density); and the body wall musculature CSA. ANOVA tests assessed associations between body composition, BMI, and menopausal status. Results: Among 180 patients, 136 (76%) had early-stage BC, and 44 (24%) had metastatic BC. Most patients were women (98%) and non-Hispanic (94%). Patients identified as White (57%), Black (29%), Asian (6%), and Other Race (8%). Sixty percent were post-menopausal. Hormone receptor-positive, HER2-positive, and triple negative subtypes were 56%, 19% and 22%, respectively. At diagnosis, 24% had a healthy BMI while 36% and 41% had overweight and obesity, respectively. All body composition measures were significantly associated with BMI (Table 1). As BMI increased, the average body wall musculature and subcutaneous, visceral, and total adipose tissue CSAs increased while the average muscle attenuation decreased. Specifically, the average visceral adipose tissue CSAs were 2.7 and 4.0-fold larger for overweight and obesity compared to that of the healthy BMI group, respectively, while their average muscle attenuations were 62.4% and 40.6% of the healthy BMI group. Postmenopausal women had 1.5-fold higher visceral adipose tissue CSA and 44.7% less average muscle attenuation compared to premenopausal women. Conclusion: Body composition correlates with all BMI categories in primarily white, non-Hispanic women with breast cancer. As BMI increases, body composition changes reliably, with increased subcutaneous and visceral adipose tissue, increased muscle area, and decreased muscle density. Muscle density, not size/area, is more associated with muscle performance, which can relate to functional status and outcomes. Despite validity concerns, BMI is an accessible and economical surrogate for body adiposity in patients with breast cancer. Postmenopausal status was also associated with greater visceral and total adiposity and lower muscle density. Further investigation is needed to confirm these findings. Table 1: Correlation between body composition, BMI, and menopausal status in patients with breast cancer All measures of body composition were significantly associated with BMI. Visceral adipose tissue increased and muscle density decreased as BMI increased and with post-menopausal status. Citation Format: Terrence Tsou, Tingchang Wang, Amanda Blackford, Ronald Summers, Vered Stearns, Jennifer Sheng. Body composition correlates with BMI and menopausal status in patients with breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-11-09.

Evaluation of the Diagnostic Utility of Selected Serum Adipokines and Cytokines in Subjects with MASLD-A Pilot Study.

Excess adipose tissue, particularly of the visceral type, triggering chronic low-grade inflammation and altering its secretory profile, is a contributing factor to the initiation and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to compare the levels of selected adipokines and cytokines in individuals with normal weight and obesity, assessing their potential for diagnosing MASLD and establishing a cutoff point for body fat content associated with hepatic steatosis development. The research involved 99 participants categorized by body mass index and MASLD presence, undergoing body composition analysis, liver elastography, biochemical tests, and evaluation of adipokines and cytokines in serum. The results indicated elevated IL-6 (interleukin 6) serum levels in individuals with obesity with MASLD compared to the normal-weight group without MASLD. The multivariate regression analysis demonstrated a connection between hepatic steatosis and total adipose tissue content, VAT (visceral adipose tissue), VAT/SAT (subcutaneous adipose tissue) ratio, HOMA-IR (homeostasis model assessment of insulin resistance), IL-6, Il-1β (interleukin 1β), and MMP-2 (matrix metalloproteinase 2). Among the adipokines and cytokines examined in this study, interleukin 6 was the strongest predictor of MASLD regardless of gender. In addition, an association between the development of hepatic steatosis and higher serum IL-1β levels and higher adipose tissue was observed in women. However, further studies on a larger group of patients are needed to consider the use of these cytokines as markers of MASLD. The HOMA-IR index demonstrated potential diagnostic utility in identifying hepatic steatosis.

Exploring the Role of Visceral Fat as a Negative Regulator of Vascular Function In Obesity

Background and Objective. Obesity promotes endothelial dysfunction, a major contributor to the development of cardiovascular disease. Work from our lab and others previously showed robust impairment of arteries embedded within visceral adipose tissue as compared to those within subcutaneous adipose tissue. Here, our research is focused on obesity-induced changes in adipose tissue gene expression, and how it may negatively or positively impact the functioning of the vascular system within the tissue. Method. Visceral adipose tissue and subcutaneous adipose tissue were extracted from lean and diet-induced obese mice after 12-14 months on respective diets (normal chow and high fat, Western diet, respectively). RNA-seq was conducted to analyze the gene expression profiles, followed by quantitative polymerase chain reaction (qPCR) to validate specific gene expression changes. Finally, Western blots were performed to evaluate if changes were occurring at the protein level. Result. We identified obesity-induced changes in over two hundred eighty genes in visceral adipose tissue and more than two hundred twenty genes in subcutaneous adipose tissue when compared to visceral and subcutaneous adipose tissue from lean mice through RNA-seq analysis. We further identified genes that are over-expressed in subcutaneous adipose tissue but not in visceral adipose tissue, and vice versa, in response to diet-induced obesity. Changes in select genes were confirmed by polymerase chain reaction as well as Western blot. Discussion and Conclusions. These data may lead to important insights into the role of the identified adipose genes as they relate to the impact on arterial function. Future directions will involve approaches that delve deeper into the molecular and physiological understanding of the roles of specific adipose genes in influencing both adipose and endothelial function of the embedded arteries. We aim to ultimately determine if identified genes upregulated only in subcutaneous adipose tissue with obesity serve to spare the embedded vasculature from endothelial dysfunction and whether overexpressing such genes can restore visceral adipose artery endothelial function in obesity. This study was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under award number 2P20GM113125 (Ibra Fancher). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Association between Visceral Adipose Tissue and Coronary Atherosclerosis in Thai Postmortem Cases

Objective: To determine the correlation between visceral adipose tissue (VAT) and degree of coronary artery stenosis in the Thai population. Materials and Methods: This prospective cross-sectional study was conducted in 220 Thai postmortem cases. Sex, age, weight, height, waist and hip circumferences were recorded for each case. The intra-abdominal VAT weight of each site was assessed during the autopsy procedure, and degrees of stenosis for three coronary arteries (left anterior descending artery (LAD), right coronary artery (RCA) and left circumflex artery (LCX)) were evaluated in histological examination. Descriptive statistics, bivariate correlation, and multivariate linear regression were used to determine the correlations between VAT and degrees of coronary artery stenosis. Results: There were 108 female and 112 male subjects with a mean age of 45.95 years old. Waist circumference, waist-hip ratio and VAT in the male subjects were significantly higher than in the female subjects (p&lt;0.001). VAT was well correlated with waist circumference and waist-hip ratio (p&lt;0.001). VAT weights were positively correlated with degrees of LAD, RCA and LCX stenosis, with coefficient correlations (r) of 0.561, 0.453 and 0.451, respectively (p&lt;0.001). Mesenteric and peri-renal adipose tissues produced better correlations than the other sites. Multivariate linear regression showed that sex and age were correlated with stenosis in all three coronary arteries (p&lt;0.001), and mesenteric and peri-renal adipose tissues had strong correlations with LAD stenosis (p&lt;0.001). Conclusion: VAT weights from all sites were correlated with degrees of coronary artery stenosis. Mesenteric and peri-renal adipose tissues produced better correlations than the other sites.

High Salt Diet Induces Aldosterone Synthase Elevation in Adrenal and Visceral Adipose Tissue - A Potential Culprit for Unsuppressed Aldosterone Levels in Female BALB/c Mice

Women are more salt-sensitive than men, irrespective of age, menopausal status, or ethnic background. Nonetheless, the mechanisms predisposing women to salt sensitivity of blood pressure (SSBP) are poorly understood, notably due to the diffculty in finding appropriate animal models. Previously, we demonstrated that female BALB/c mice spontaneously develop SSBP, likely through an inability to reduce the expression of adrenal aldosterone synthase (CYP11B2) appropriately, which leads to unsuppressed aldosterone levels in response to high salt intake. Herein, we aim to decipher the mechanism involved in SSBP in female BALB/c mice by comparing them to female salt-resistant C57BL/6 mice. Eleven-week-old female BALB/c and C57BL/6J mice were fed either a normal (0.4%, NSD) or a high salt diet (4%, HSD) for seven days. HSD significantly reduced adrenal aldosterone synthase transcript and protein expression in female C57BL/6 mice compared to those on a NSD. Conversely, HSD substantially increased CYP11B2 levels in BALB/c female mice when compared to strain-matched NSD and C57BL/6 NSD mice (2-way ANOVA, p&lt;0.05). HSD induced a more significant aldosterone drop in C57BL/6 versus BALB/c mice (C57BL/6: 72% vs. BALB/c: 49%). Remarkably, HSD led to an increase in CYP11B2 in the visceral adipose tissue (VAT) of BALB/c mice in comparison to strain-matched NSD mice, while no such alteration was observed between C57BL/6 NSD and HSD. We previously showed that leptin regulates CYP11B2 expression. We report here that HSD increased leptin receptor (lepR) expression in adrenal and VAT from BALB/c mice in comparison to both strain-matched NSD and C57BL/6 NSD. Baseline levels of leptin were similar in C57BL/6 and BALB/c mice. However, BALB/c mice on HSD displayed increased levels of leptin compared to its strain-matched NSD mice, while no such alteration was observed in C57BL/6 mice. Furthermore, female BALB/c mice on HSD displayed elevated endothelial cell-specific mineralocorticoid receptor (ECMR) expression compared to female C57BL/6 NSD and HSD mice (2-way ANOVA, p&lt;0.05). Endothelium-dependent relaxation to acetylcholine was significantly reduced in the female BALB/c mice on HSD compared to strain-matched NSD and C57BL/6 NSD (n = 3, 2-way ANOVA, P &lt; 0.05). Interestingly, on NSD, C57BL/6 mice present a better endothelial function than BALB/c, which was not altered by HSD. Collectively, our data supports an overactivation of the leptin-CYP11B2-aldosterone axis in both adrenals and VAT, leading to inappropriate aldosterone levels, which, associated with higher ECMR expression, induce endothelial dysfunction in BALB/c mice. Together, these mechanisms are likely the cause of SSBP in female BALB/c mice. Funding: R01HL130301, R01HL155265 (E.J.B.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Acute and chronic hyperglycemia blunts microvascular reactivity in postmenopausal women with type 2 diabetes

Type 2 diabetes (T2D) is strongly associated with increased risk of cardiovascular diseases via endothelial dysfunction. Hyperglycemia causes microvascular endothelial dysfunction and reduces muscle perfusion. Near-infrared spectroscopy (NIRS) measures microvascular reactivity in skeletal muscle during vascular occlusion/reperfusion. However, the impact of acute and chronic hyperglycemia on macrovascular endothelial function (brachial flow-mediated dilation, FMD) and microvascular reactivity (NIRS-derived tissue oxygen saturation index, TOI) has not been examined in postmenopausal women with and without T2D. We hypothesized that T2D women would have decreased FMD and TOI responsiveness in the fasted condition and greater vascular impairments during acute hyperglycemia compared to controls.Ten T2D (61 ± 5 years) and 10 normoglycemic postmenopausal women (CON, 62 ± 7 years) participated in the study. Hemoglobin A1C (HbA1C) and blood glucose were measured by finger prick at baseline (fasted condition). Brachial artery FMD was evaluated using ultrasound. Forearm muscle TOI magnitude and slope during arterial occlusion and reperfusion periods were measured using NIRS. An oral glucose tolerance test (OGTT) was performed to induce acute hyperglycemia. Blood glucose, FMD, and TOI were measure at baseline and 1 hour (1-h) after OGTT. Abdominal fat was assessed by waist circumference and visceral adipose tissue (VAT) obtained by a whole-body dual-energy X-ray absorptiometry scan.Fasting HbA1C and glucose, waist circumference, and VAT were higher in T2D compared to CON (all p &lt; 0.05). The increase in blood glucose at 1-h was higher in T2D (Δ143 ± 15 mg/dl) compared to CON (Δ49 ± 5 mg/dl) (p &lt; 0.01). FMD at baseline and the decreases in FMD at 1-h were similar in T2D (Δ-2.2 ± 0.2%) and CON groups (Δ-1.9 ± 0.4%) (all p &lt; 0.01). At baseline, T2D showed blunted TOI occlusion magnitude (T2D: -16 ± 1 vs. CON: -21 ± 2%), TOI occlusion slope (T2D: -0.05 ± 0.01 vs. CON: -0.07 ± 0.01), TOI reperfusion magnitude (T2D: 21 ± 2 vs. CON: 32 ± 3%), and TOI reperfusion slope (T2D: 0.79 ± 0.10 vs. CON: 1.19 ± 0.14) compared to CON (all p &lt; 0.05). At 1-h, T2D exhibited lower TOI occlusion magnitude (T2D: -17 ± 2 vs. CON: -24 ± 3%), TOI occlusion slope (T2D: -0.06 ± 0.01 vs. CON: -0.08 ± 0.01), TOI reperfusion magnitude (T2D: 23 ± 2 vs. CON: 33 ± 4%), and TOI reperfusion slope (T2D: 0.90 ± 0.19 vs. CON: 1.14 ± 0.15) compared to CON (all p &lt; 0.05). HbA1C, a measure of chronic hyperglycemia, was positively correlated with VAT (r = 0.514, p = 0.02) and TOI occlusion slope (r = 0.460, p = 0.04) and negatively correlated with TOI reperfusion magnitude (r = -0.506, p = 0.02) and slope at baseline (r = -0.493, p = 0.03). In conclusion, women with T2D exhibited blunted microvascular reactivity despite similar FMD compared with normoglycemic women in the fasted condition. Acute hyperglycemia further blunted microvascular function, but not macrovascular endothelial function, in women with T2D. Blunted microvascular reactivity was associated with chronic hyperglycemia and elevated VAT in postmenopausal women. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Endothelin A Receptor Activation on Vascular Smooth Muscle Cells Mediates Visceral Adipose Tissue Inflammation in an Obese Mouse Model

Obesity causes a pro-inflammatory shift in visceral adipose tissue immune cells that is thought to promote adipocyte dysfunction and obesity pathophysiology. Endothelin-1 (ET-1) is a small peptide produced mostly by endothelial cells that causes inflammation in diseases including a number of nephropathies and autoimmune diseases. ET-1 is increased in obese patients and in rodent models of obesity. Our lab has demonstrated that mice fed high fat diet (HFD) have an increase in visceral adipose tissue CD4+ and CD8+ T cells and a reduction in anti-inflammatory eosinophils that is attenuated by treatment with an ET-1 type A receptor (ETAR) antagonist; however, the mechanisms by which ET-1 leads to inflammation remain unknown. The ETAR is highly abundant on vascular smooth muscle cells (VSMC), where activation causes a significant increase in pro-inflammatory interleukin-6 production. We hypothesized that elevated ET-1 production in visceral adipose causes a pro-inflammatory shift in tissue immune cells by activating VSMC ETAR. To test this hypothesis, 8-week-old floxed control and vascular smooth muscle cell-specific ETA knockout (SMAKO) mice were placed on either normal (n=5 and 3 for control and SMAKO respectively) or high-fat diet (n=6 and 4 for control and SMAKO respectively) for 12 weeks. Tissue immune cells were quantified by flow cytometry. As expected, HFD fed mice had significantly increased body weight, lean mass, and fat mass, as measured by EchoMRI, compared to NMD fed mice; however, there was no detectable difference due to genotype. There was a significant increase in CD4+ T cells (control NMD: 2.45 ± 0.28 vs. control HFD: 4.37 ± 0.80 % of CD45+ cells; SMAKO NMD: 0.94 ± 0.52 vs. SMAKO HFD: 2.24 ± 0.40 % of CD45+ cells; pint=0.63, pdiet=0.02*, pgenotype=0.01*) and CD8+ T cells (control NMD: 0.49 ± 0.10 vs. control HFD: 2.02 ± 0.59 % of CD45+ cells; SMAKO NMD: 0.12 ± 0.07 vs. SMAKO HFD: 0.52 ± 0.07 % of CD45+ cells; pint=0.20, pdiet=0.04*, pgenotype=0.04*) that was significantly attenuated in SMAKO mice. In addition, HFD fed control mice had a greater reduction in eosinophils compared to NMD floxed control. The reduction in eosinophils was attenuated in SMAKO (control NMD: 5.28 ± 2.01 vs. control HFD: 1.28 ± 0.07 % of CD45+ cells; SMAKO NMD: 5.92 ± 0.94 vs. SMAKO HFD: 4.49 ± 1.60 % of CD45+ cells; pint=0.42, pdiet=0.09, pgenotype=0.23). These data suggest that ET-1-induced adipose tissue inflammation in obese mice occurs via activation of ETAR on VSMCs. R01DK124437, P30GM149404, and T32HL105324. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Long-Term Improvement in Cardiorespiratory Fitness Ameliorates Insulin Sensitivity beyond Changes in Visceral/Ectopic Fat among Men with Visceral Obesity.

The SYNERGIE study documented the effects on cardiometabolic risk (CMR) indices of a 1-year lifestyle intervention targeting physical activity (PA) and diet followed by a 2-year maintenance period in men with visceral obesity. Improvements in CMR markers and a decrease in low-attenuation muscle (LAM) area were observed after 1 year. Despite a rebound in visceral adipose tissue (VAT) during the maintenance period, insulin resistance (IR) improved. We tested the hypothesis that variations in cardiorespiratory fitness (CRF) and LAM could explain the long-term improvement in IR. A health (n = 88; mean age 49.0 ± 8.2 years) and fitness (n = 72) evaluation was performed at 0, 1, and 3 years. Participants were classified into two groups based on their CRF response over the maintenance period (worsening: CRF- vs. maintenance/improvement: CRF+). During the maintenance period, changes in the psoas and core LAM areas correlated with changes in IR (r = 0.27; p < 0.05 and r = 0.34; p < 0.005) and changes in CRF (r = -0.31; p < 0.01 and r = -0.30; p < 0.05). IR improved in the CRF+ group (p < 0.05) but remained stable in the CRF- group. Men in the CRF+ group regained half of the changes in VAT volume and LAM at the psoas and mid-thigh compared to the CRF- group (p < 0.05). These results support the importance of targeting VAT and CRF/PA for the long-term management of CMR in men with visceral obesity.

Time-Restricted Feeding Induces Beiging and Rejuvenates Adipose Tissue with Beneficial Effects on Cerebral Function in Old Mice

Adipose tissue, traditionally viewed as purely an energy reserve, has recently been unveiled as a critical endocrine organ. Through the secretion of bioactive molecules known as adipokines, adipose tissue plays a role in inter-organ communication, most notably with the brain to maintain metabolic homeostasis and cognitive function. Aberrant adipokine secretion or signaling, often exacerbated with aging, has emerged as a defining characteristic of dysfunctional adipose tissue. This dysregulation can lead to inflammatory conditions, potentially disrupting neural homeostasis and heightening the vulnerability of older individuals to cognitive impairments. This study investigated the capacity of time-restricted feeding (TRF) to promote beiging (induction of brown adipocytes positive for uncoupling protein 1(UCP1) within white adipose tissue depots) in aged mice, exploring its potential role in modulating adipokine profiles, attenuating inflammation, and mitigating age-associated cognitive decline. To test this hypothesis, we collected adipose tissue samples from 24-month-old mice that underwent 6 months of TRF and compared their profiles to both young and age-matched controls on an unrestricted (ad-lib) diet. Immunohistochemical analyses of brown adipose tissue (BAT), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) revealed a marked reduction in pro-inflammatory markers CD80 and F4/80hi across all adipose tissues. Notably, a shift towards an anti-inflammatory state was indicated by a pronounced increase in CD163 staining in the SAT and VAT. Additionally, the increased expression of UCP1, especially in BAT and SAT, pointed towards an enhanced thermogenic capacity, suggesting a potential metabolic advantage. This was further reinforced by an increase in electron transport chain (ETC) activity in all adipose tissues. These findings have powerful implications given the established links between systemic inflammation, disrupted adipokine signaling, and neurodegenerative conditions. The alleviated adipose inflammatory profiles measured in TRF mice not only underscore its potential metabolic benefits but also highlight its possible role in safeguarding cognitive health, especially in an aging demographic. Currently serum studies and RNA sequencing are being conducted to look at altered transcript production and to investigate the role of adipokines on the brain health of the aged TRF mice. Such insights pave the way for future research exploring dietary strategies to combat age-related cognitive decline. Stephenson Cancer Center, National Institute on Aging R03 AG070479, American Heart Association. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Different Effects of Obesity and Fasting on the Expression of Type 3 Deiodinase and Thyroid Hormone Receptors in the Liver and Visceral Adipose Tissue of C57BL/6 Male Mice.

Energy status can alter thyroid hormone signalling in different tissues. Little is known about the effect of fasting on the local thyroid hormone metabolism under high-fat diet (HFD)-induced obesity. We aimed to investigate the fasting effect on deiodinase type 3 (DIO3) and thyroid hormone receptors (TRs) expression in liver and visceral adipose tissue (VAT) of HFD-induced obese mice. The 30 male C57BL/6 mice were divided into three groups (n = 10/group): control (CON) group, obese (OB) group, and fasted obese (OBF) group. In a 14-week study, the expression levels of DIO3 and TRs in the liver and VAT of mice were measured by real-time polymerase chain reaction. Gene expression results were shown as fold changes defined by 2-ΔΔct. Comparison between groups was performed by using one-way-ANOVA or Kruskal-Wallis ANOVA test. In the liver, there was a significantly lower expression of DIO3 and higher expression of TRs in obese fasted mice compared to obese mice. Compared to the lean mice, OBF mice had significantly lower expression of DIO3 and higher expression of TRβ. In the VAT, mRNA expression of DIO3 was significantly increased in OBF and OB groups compared to the CON group. There were no significant differences in the mRNA expression of TRs between groups. Our findings suggest that fasting may be more effective in improving thyroid hormone metabolism in the liver rather than the VAT of obese mice.