The pathophysiology of visceral adipose tissues in cardiometabolic diseases.

Central pattern of fat distribution, especially fat accumulation within the intraabdominal cavity increases risks for cardiometabolic diseases. Portal hypothesis combined with a pathological remodeling in visceral fat is considered the major etiological factor explaining the independent contribution of visceral obesity to cardiometabolic diseases. Excessive remodeling in visceral fat during development of obesity leads to dysfunctions in the depot, characterized by hypertrophy and death of adipocytes, hypoxia, inflammation, and fibrosis. Dysfunctional visceral fat secretes elevated levels of fatty acids, glycerol, and proinflammatory and profibrotic cytokines into the portal vein directly impacting the liver, the central regulator of systemic metabolism. These metabolic and endocrine products induce ectopic fat accumulation, insulin resistance, inflammation, and fibrosis in the liver, which in turn causes or exacerbates systemic metabolic derangements. Elucidation of underlying mechanisms that lead to the pathological remodeling and higher degree of dysfunctions in visceral adipose tissue is therefore, critical for the development of therapeutics to prevent deleterious sequelae in obesity. We review depot differences in metabolic and endocrine properties and expendabilities as well as underlying mechanisms that contribute to the pathophysiological aspects of visceral adiposity in cardiometabolic diseases. We also discuss impacts of different weight loss interventions on visceral adiposity and cardiometabolic diseases.

Human recombinant relaxin-2 (serelaxin) regulates the proteome, lipidome, lipid metabolism and inflammatory profile of rat visceral adipose tissue.

Recombinant human relaxin-2 (serelaxin) has been widely proven as a novel drug with myriad effects at different cardiovascular levels, which support its potential therapeutic efficacy in several cardiovascular diseases (CVD). Considering these effects, together with the influence of relaxin-2 on adipocyte physiology and adipokine secretion, and the connection between visceral adipose tissue (VAT) dysfunction and the development of CVD, we could hypothesize that relaxin-2 may regulate VAT metabolism. Our objective was to evaluate the impact of a 2-week serelaxin treatment on the proteome and lipidome of VAT from Sprague-Dawley rats. We found that serelaxin increased 1 polyunsaturated fatty acid and 6 lysophosphatidylcholines and decreased 4 triglycerides in VAT employing ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) based platforms, and that regulates 47 phosphoproteins using SWATH/MS analysis. Through RT-PCR, we found that serelaxin treatment also caused an effect on VAT lipolysis through an increase in the mRNA expression of hormone-sensitive lipase (HSL) and a decrease in the expression of adipose triglyceride lipase (ATGL), together with a reduction in the VAT expression of the fatty acid transporter cluster of differentiation 36 (Cd36). Serelaxin also caused an anti-inflammatory effect in VAT by the decrease in the mRNA expression of tumor necrosis factor α (TNFα), interleukin-1ß (IL-1ß), chemerin, and its receptor. In conclusion, our results highlight the regulatory role of serelaxin in the VAT proteome and lipidome, lipolytic function, and inflammatory profile, suggesting the implication of several mechanisms supporting the potential benefit of serelaxin for the prevention of obesity and metabolic disorders.

Waist Circumference as a Tool for Identifying Visceral Fat in Women with Non-Metastatic Breast Cancer.

Abdominal adiposity is associated with tumor development and poor clinical outcomes in breast cancer (BC) and can be identified by the measurement of waist circumference (WC) and visceral adipose tissue (VAT). This study aimed to evaluate the association between waist circumference (WC) and imaging measurement of central adiposity according to age group in women with BC. Abdominal adiposity was assessed by WC and VAT, obtained by dual-energy X-ray absorptiometry (DXA). Body mass index (BMI) was assessed. The presence of inflammation was investigated by measuring C-Reactive Protein (CRP) levels. Multivariate linear regression models were applied to verify the association between WC and VAT. The significance level adopted for all tests was 5%. This study included 112 women with a mean age of 55.5 ± 11.4 years. After adjusted models, WC remained associated with VAT and for every centimeter increase in WC, there was an increase of 3.12 cm2 (CI: 2.40 - 3.85; p < 0.001) in VAT. WC was associated with VAT in women with breast cancer, proving to be a simple, fast, and noninvasive approach that can be used as a proxy to identify visceral fat.

Errate: Dysregulation of Inflammation, Oxidative Stress, and Glucose Metabolism-Related Genes and miRNAs in Visceral Adipose Tissue of Women with Type 2 Diabetes Mellitus.

The authors informed the journal that errors occurred in their manuscript, and were not noticed by the authors during the proofreading. Corrections: 1. Figure 1, top entry: "Predipocytes" should read "Preadipocytes". 2. Figure 3, chart "TIGAR": "-9" value on y axis should read "-8". 3. Figure 4, chart "let-7g-5p": the upper "-4" value on y axis should read "0". 4. Figure 5: the title of the bottom right chart should read "TIGAR". 5. Figure 6, chart "miR-26a-5p": the values on y axis should read from the top: 2, 1, 0, -1, -2. 6. Figure 6, chart "miR-374a-5p": the values on y axis should read from the top: 0, -1, -2, -3, -4. 7. Table 4., in the 6 rows from the bottom: in column "miRNAs", "hsa-miR-21-5" should read "hsa-miR-21-5p". 8. Supplementary Table1, 1st column on the left: "TG-HDL" should read "TG/HDL" Reference: Adam Wróblewski, Justyna Strycharz, Katarzyna Oszajca, Piotr Czarny, Ewa Swiderska, Tomasz Matyjas, Andrzej Zieleniak, Monika Rucinska, Lech Pomorski, Józef Drzewoski, Agnieszka Sliwinska, Janusz Szemraj: Dysregulation of Inflammation, Oxidative Stress, and Glucose Metabolism-Related Genes and miRNAs in Visceral Adipose Tissue of Women with Type 2 Diabetes Mellitus. Med Sci Monit, 2023; 29: e939299. DOI: 10.12659/MSM.939299.

Altered extracellular matrix dynamics is associated with insulin resistance in adolescent children with obesity.

OBJECTIVE: The objective of this study was to examine the hypothesis that abdominal and gluteal adipocyte turnover, lipid dynamics, and fibrogenesis are dysregulated among insulin-resistant (IR) compared with insulin-sensitive (IS) adolescents with obesity. METHODS: Seven IS and seven IR adolescents with obesity participated in a 3-h oral glucose tolerance test and a multi-section magnetic resonance imaging scan of the abdominal region to examine body fat distribution patterns and liver fat content. An 8-week 70% deuterated water (2 H2 O) labeling protocol examined adipocyte turnover, lipid dynamics, and fibrogenesis in vivo from biopsied abdominal and gluteal fat. RESULTS: Abdominal and gluteal subcutaneous adipose tissue (SAT) turnover rates of lipid components were similar among IS and IR adolescents with obesity. However, the insoluble collagen (type I, subunit α2) isoform measured from abdominal, but not gluteal, SAT was elevated in IR compared with IS individuals. In addition, abdominal insoluble collagen Iα2 was associated with ratios of visceral-to-total (visceral adipose tissue + SAT) abdominal fat and whole-body and adipose tissue insulin signaling, and it trended toward a positive association with liver fat content. CONCLUSIONS: Altered extracellular matrix dynamics, but not expandability, potentially decreases abdominal SAT lipid storage capacity, contributing to the pathophysiological pathways linking adipose tissue and whole-body IR with altered ectopic storage of lipids within the liver among IR adolescents with obesity.

Visceral and subcutaneous abdominal fat is associated with non-alcoholic fatty liver disease while augmenting Metabolic Syndrome's effect on non-alcoholic fatty liver disease: A cross-sectional study of NHANES 2017-2018.

BACKGROUND: The aim was to evaluate the effect different types of abdominal fat have on NAFLD development and the effects of abdominal fat has on the association between Metabolic Syndrome (MetS) and NALFD. METHODS: Data was collected from the cross-sectional NHANES dataset (2017-2018 cycle). Using the controlled attenuation parameter (USG CAP, dB/m), which measures the level of steatosis, the cohort was stratified into two groups: NAFLD(+) (≥274 dB/m) and NAFLD(-). Using complex samples analyses, associations between liver steatosis or NAFLD and types of abdominal fat area [Total abdominal (TAFA), subcutaneous (SAT), and visceral (VAT)] were determined. Pearson's correlation coefficient (r) was calculated to evaluate the associations between adipose tissues and NAFLD. Logistic regression was used to determine the risk [odds ratio (OR) and 95% confidence interval (95%CI)]. Participants were also classified by MetS, using the Harmonizing Definition criteria. RESULTS: Using 1,980 participants (96,282,896 weighted), there was a significant (p<0.001) correlation between USG CAP and TAFA (r = 0.569), VAT (r = 0.645), and SAT (r = 0.479). Additionally, the risk of developing NAFLD was observed for total abdominal obesity (OR = 19.9, 95%CI: 5.1-77.8, p<0.001), visceral obesity (OR = 9.1, 95%CI: 6.2-13.5, p<0.001) and subcutaneous obesity (OR = 4.8, 95%CI: 3.2-6.9, p<0.001). Using 866 participants (44,399,696 weighted), for visceral obesity, participants with MetS and visceral obesity (OR = 18.1, 95%CI: 8.0-41.3, p<0.001) were shown to have a greater risk than participants with MetS only (OR = 6.3, 95%CI: 2.6-15.2, p<0.001). For subcutaneous obesity, again, participants with MetS and subcutaneous obesity (OR = 18.3, 95%CI: 8.0-41.9, p<0.001) were shown to have a greater risk than the MetS-only group (OR = 10.3, 95%CI: 4.8-22.4, p<0.001). CONCLUSION: TAFA, VAT, and SAT were positively associated with USG CAP values and increased the risk of developing NAFLD. Also, the type of abdominal fat depots did affect the association between MetS and NAFLD.

Visceral adiposity associated with incidence and development trajectory of cardiometabolic diseases: A prospective cohort study.

BACKGROUND AND AIMS: There is a lack of literature concerning the effects of visceral adipose on the development of first cardiometabolic disease (FCMD) and its subsequent progression to cardiometabolic multimorbidity (CMM) and mortality. METHODS AND RESULTS: 423,934 participants from the UK Biobank with different baseline disease conditions were included in the analysis. CMM was defined as the simultaneous presence of coronary heart disease, T2D, and stroke. Visceral adiposity was estimated by calculating the visceral adiposity index (VAI). Multistate models were used to assess the effect of visceral adiposity on the development of CMM. During a median follow-up of 13.5 years, 50,589 patients had at least one CMD, 6131 were diagnosed with CMM, whereas 24,634 patients died. We observed distinct roles of VAI with respect to different disease transitions of CMM. HRs (95 % CIs) of high VAI were 2.35 (2.29-2.42) and 1.64 (1.50-1.79) for transitions from healthy to FCMD and from FCMD to CMM, and 0.97 (0.93-1.02) for all-cause mortality risk from healthy, FCMD and CMM, respectively. CONCLUSIONS: Our study provides the first evidence that visceral adipose may contribute to the development of FCMD and CMM in healthy participants. However, visceral adipose may confer resistance to all-cause mortality in participants with existing CMD or CMM. A better understanding of the relationship between visceral adipose and CMM can focalize further investigations on patients with CMD with high levels of visceral fat and help take targeted preventive measures to reduce the medical burden on individual patients and society.

The CD27/CD70 pathway negatively regulates visceral adipose tissue-resident Th2 cells and controls metabolic homeostasis.

Adipose tissue homeostasis relies on the interplay between several regulatory lineages, such as type 2 innate lymphoid cells (ILC2s), T helper 2 (Th2) cells, regulatory T cells, eosinophils, and type 2 macrophages. Among them, ILC2s are numerically the dominant source of type 2 cytokines and are considered as major regulators of adiposity. Despite the overlap in immune effector molecules and sensitivity to alarmins (thymic stromal lymphopoietin and interleukin-33) between ILC2s and resident memory Th2 lymphocytes, the role of the adaptive axis of type 2 immunity remains unclear. We show that mice deficient in CD27, a member of the tumor necrosis factor receptor superfamily, are more resistant to obesity and associated disorders. A comparative analysis of the CD4 compartment of both strains revealed higher numbers of fat-resident memory Th2 cells in the adipose tissue of CD27 knockout mice, which correlated with decreased programmed cell death protein 1-induced apoptosis. Our data point to a non-redundant role for Th2 lymphocytes in obesogenic conditions.

Behind BMI: The Potential Indicative Role of Abdominal Ectopic Fat on Glucose Metabolism.

INTRODUCTION: The purpose of this study was to compare the difference in abdominal fat distribution between different metabolic groups and find the ectopic fat with the most risk significance. METHODS: A total of 98 subjects were enrolled; there were 53 cases in the normal glucose metabolism group and 45 cases in the abnormal glucose metabolism group. Chemical shift-encoded magnetic resonance imaging was applied for quantification of pancreatic fat fraction (PFF) and hepatic fat fraction (HFF), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT). The correlation and the difference of fat distribution between different metabolism groups were analyzed. The receiver operating characteristic (ROC) curve was used to analyze the suggestive effect of different body fat fraction. RESULTS: Correlation analysis showed that body mass index (BMI) had the strongest correlation with fasting insulin (r = 0.473, p < 0.001), HOMA-IR (r = 0.363, p < 0.001), and C-reactive protein (r = 0.245, p < 0.05). Pancreatic fat has a good correlation with fasting blood glucose (r = 0.247, p < 0.05) and HbA1c (r = 0.363, p < 0.001). With the increase of BMI, PFF, VAT, and SAT showed a clear upward trend, but liver fat was distributed relatively more randomly. The pancreatic fat content in the abnormal glucose metabolism group is significantly higher than that in the normal group, and pancreatic fat is also a reliable indicator of abnormal glucose metabolism, especially in the normal and overweight groups (the area under the curve was 0.859 and 0.864, respectively). CONCLUSION: MR-based fat quantification techniques can provide additional information on fat distribution. There are differences in fat distribution among people with different metabolic status. People with more severe pancreatic fat deposition have a higher risk of glucose metabolism disorders.

Cutoffs of different body measurement indexes of central obesity in patients with type 2 diabetes.

Few research discuss whether the body measurement indexs of obesity in general populations is applicable to patients with type 2 diabetes. We explore the optimal cutoffs of visceral fat area (VFA) and subcutaneous fat area (SFA) in the diagnosis of central obesity and the cutoffs of corresponding waist circumference (WC) and body mass index (BMI) in patients with Type 2 Diabetes (T2D). Cross-sectional cohort study. 1057 patients with T2D (550 males and 507 females) aged 18 or above that satisfied the criteria were included. The definition and diagnostic criteria of Metabolic syndrome (Mets) were analyzed according to the 2020 Chinese Diabetes Society (CDS) Guideline. The VFA and SFA were measured by bioelectrical impedance analysis (BIA). The optimal VFA and SFA cutoffs and corresponding WC and BMI when two or more nonadipose components of MetS (without central obesity) were met were analyzed by ROC curve. Among all of the T2D patients, the optimal VFA cutoff for identifying two or more nonadipose components of MetS was 73.30 cm2 for females and 69.20 cm2 for males, while the optimal SFA cutoff was 186.70 cm2 for females and 123.30 cm2 for males. The ROC area under curve (AUC) of VFA for identifying two or more nonadipose components of MetS was higher than that of SFA (Female: 0.65 vs. 0.58, P = 0.01). The VFA cutoff of newly diagnosed T2D patients (females = 86.10 cm2, males = 69.00 cm2) was higher than that of non-newly diagnosed T2D patients (females = 73.30 cm2, males = 65.40 cm2). A stratification analysis of gender and whether newly diagnosed with T2D or not showed that the WCs corresponding to VFA were 85.00 cm and BMI was about 24.00 kg/m2. VFA measured by BIA can be a non-invasive method to detect central obesity in patients with T2D, the corresponding WC were 85.00 cm and BMI was 24.00 kg/m2.

The role of adipogenic capacity and dysfunctional subcutaneous adipose tissue in the inheritance of type 2 diabetes mellitus: cross-sectional study.

OBJECTIVE: This study tested the hypothesis that limited subcutaneous adipose tissue (SAT) expansion represents a primary predisposition to the development of type 2 diabetes mellitus (T2DM), independent of obesity, and identified novel markers of SAT dysfunction in the inheritance of T2DM. METHODS: First-degree relatives (FDR) of T2DM patients (n = 19) and control individuals (n = 19) without obesity (fat mass < 25%) were cross-sectionally compared. Body composition (bioimpedance, computed tomography) and insulin sensitivity (IS; oral glucose tolerance test, clamp) were measured. SAT obtained by needle biopsy was used to analyze adipocyte size, lipidome, mRNA expression, and inflammatory markers. Primary cultures of adipose precursors were analyzed for adipogenic capacity and metabolism. RESULTS: Compared with control individuals, FDR individuals had lower IS and a higher amount of visceral fat. However, SAT-derived adipose precursors did not differ in their ability to proliferate and differentiate or in metabolic parameters (lipolysis, mitochondrial oxidation). In SAT of FDR individuals, lipidomic and mRNA expression analysis revealed accumulation of triglycerides containing polyunsaturated fatty acids and increased mRNA expression of lysyl oxidase (LOX). These parameters correlated with IS, visceral fat accumulation, and mRNA expression of inflammatory and cellular stress genes. CONCLUSIONS: The intrinsic adipogenic potential of SAT is not affected by a family history of T2DM. However, alterations in LOX mRNA and polyunsaturated fatty acids in triacylglycerols are likely related to the risk of developing T2DM independent of obesity.

Change in abdominal obesity after colon cancer surgery - effects of left-sided and right-sided colonic resection.

BACKGROUND: Excess abdominal visceral adipose tissue (VAT) is associated with metabolic diseases and poor survival in colon cancer (CC). We assessed the impact of different types of CC surgery on changes in abdominal fat depots. MATERIAL AND METHODS: Computed tomography (CT)-scans performed preoperative and 3 years after CC surgery were analyzed at L3-level for VAT, subcutaneous adipose tissue (SAT) and total adipose tissue (TAT) areas. We assessed changes in VAT, SAT, TAT and VAT/SAT ratio after 3 years and compared the changes between patients who had undergone left-sided and right-sided colonic resection in the total population and in men and women separately. RESULTS: A total of 134 patients with stage I-III CC undergoing cancer surgery were included. Patients who had undergone left-sided colonic resection had after 3 years follow-up a 5% (95% CI: 2-9%, p < 0.01) increase in abdominal VAT, a 4% (95% CI: 2-6%, p < 0.001) increase in SAT and a 5% increase (95% CI: 2-7%, p < 0.01) in TAT. Patients who had undergone right-sided colonic resection had no change in VAT, but a 6% (95% CI: 4-9%, p < 0.001) increase in SAT and a 4% (95% CI: 1-7%, p < 0.01) increase in TAT after 3 years. Stratified by sex, only males undergoing left-sided colonic resection had a significant VAT increase of 6% (95% CI: 2-10%, p < 0.01) after 3 years. CONCLUSION: After 3 years follow-up survivors of CC accumulated abdominal adipose tissue. Notably, those who underwent left-sided colonic resection had increased VAT and SAT, whereas those who underwent right-sided colonic resection demonstrated solely increased SAT.

The interaction between MALAT1 and TUG1 with dietary fatty acid quality indices on visceral adiposity index and body adiposity index.

We aimed to investigate the interaction between the transcript levels of taurine-upregulated gene 1 (TUG1) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and the Cholesterol-Saturated Fat Index (CSI) in relation to the visceral adiposity index (VAI) and body adiposity index (BAI). This cross-sectional study involved 346 women classified as obese and overweight, aged between 18 and 48 years. Dietary intake and the quality of dietary fat were assessed using a validated and reliable 147-item semi-quantitative food frequency questionnaire, with the Cholesterol-Saturated Fat Index (CSI) used as an indicator. Transcription levels of MALAT1 and TUG1 were evaluated through real-time polymerase chain reaction following the criteria outlined in the Minimum Information for Publication of Quantitative standards. Serum profiles were measured using standard protocols. We observed a positive association between transcription level of MALAT1 and VAI in both crude (ß = 3.646, 95% CI 1.950-5.341, p < 0.001) and adjusted (ß = 8.338, 95% CI 6.110-10.566, p < 0.001) models. Furthermore, after adjusting for confounders, a significant positive interaction was noted between MALAT1 expression and CSI on BAI (ß: 0.130, 95% CI 0.019, 0.240, p = 0.022), with a marginal positive interaction observed on VAI (ß: 0.718, 95% CI - 0.028, 1.463, p = 0.059). It seems that there may be a positive interaction between MALAT1 transcription level and CSI on VAI and BAI among overweight and obese women. However, no associations were seen between TUG1 mRNA level and the above-mentioned outcomes. Further functional studies are still required to elucidate this concept.

Characteristics of Abdominal Visceral Adipose Tissue, Metabolic Health and the Gut Microbiome in Adults.

CONTEXT: Compared with the relatively benign effects of increased subcutaneous adipose tissue (SAT), increased visceral adipose tissue (VAT) volume is a causal risk factor for hypertension, hyperlipidemia, type 2 diabetes, and cardiovascular disease. In rodents, increased VAT volume and triglyceride density and ectopic lipid accumulation in kidneys and liver have been induced by alterations in the gut microbiome. However, few studies have characterized these relationships in humans. OBJECTIVE: To evaluate the tissue triglyceride content of VAT and SAT, liver, kidneys, and pancreas in male and female adults and assess associations with markers of glucose tolerance, serum insulin, and lipids and characteristics of the gut microbiome. METHODS: Cross-sectional observational study of healthy human adults (n = 60) at a clinical research center. Body mass index (BMI), body composition, and oral glucose tolerance were assessed. Microbiome analysis was conducted on stool samples using 16S rRNA v3 amplicon sequencing. The triglyceride content of VAT, SAT, liver, kidney and pancreas were determined by assessing proton density fat fraction (PDFF) with magnetic resonance imaging (MRI). RESULTS: Higher VAT PDFF and the ratio of VAT to SAT PDFF were related to higher BMI, HbA1c, HOMA-IR, non-high-density lipoprotein cholesterol, plasma triglycerides, low-density lipoprotein (LDL) cholesterol, and lower high-density lipoprotein (HDL) cholesterol. A higher VAT PDFF and VAT to SAT PDFF ratio were associated with lower alpha diversity and altered beta diversity of the gut microbiome. Differences in VAT were associated with higher relative abundance of the phylum Firmicutes, lower relative abundance of the phylum Bacteroidetes, and enrichment of the bacterial genera Dorea, Streptococcus, and Solobacterium. CONCLUSION: VAT PDFF measured with MRI is related to impaired glucose homeostasis, dyslipidemia, and differences in the gut microbiome, independently of the total body fat percentage.

The gut microbiome modulates associations between adherence to a Mediterranean-style diet, abdominal adiposity, and C-reactive protein in population-level analysis.

BACKGROUND: Adherence to a Mediterranean-style dietary pattern is likely to have variable effects on body composition, but the impact of gut microbiome on this relationship is unknown. OBJECTIVES: To examine the potential mediating effect of the gut microbiome on the associations between Alternate Mediterranean Diet (aMed) scores, abdominal adiposity, and inflammation in population-level analysis. DESIGN: In a community-based sample aged 25 to 83 y (n = 620; 41% female) from Northern Germany, we assessed the role of the gut microbiome, sequenced from 16S rRNA genes, on the associations between aMed scores, estimated using validated food-frequency questionnaires, magnetic resonance imaging-determined visceral (VAT) and subcutaneous (SAT) adipose tissue and C-reactive protein (CRP). RESULTS: Higher aMed scores were associated with lower SAT (-0.86 L (95% CI: -1.56, -0.17), P = 0.01), VAT (-0.65 L (95% CI: -1.03,-0.27), P = 0.01) and CRP concentrations (-0.35 mg/L; ß: -20.1% (95% CI: 35.5, -1.09), P = 0.04) in the highest versus lowest tertile after multivariate adjustment. Of the taxa significantly associated with aMed scores, higher abundance of Porphyromonadaceae mediated 11.6%, 9.3%, and 8.7% of the associations with lower SAT, VAT, and CRP, respectively. Conversely, a lower abundance of Peptostreptococcaceae mediated 13.1% and 18.2% of the association with SAT and CRP levels. Of the individual components of the aMed score, moderate alcohol intake was associated with lower VAT (-0.2 (95% CI: -0.4, -0.1), P =0.01) with a higher abundance of Oxalobacteraceae and lower abundance of Burkholderiaceae explaining 8.3% and 9.6% of this association, respectively. CONCLUSION: These novel data suggest that abundance of specific taxa in the Porphyromonadaceae and Peptostreptococcaceae families may contribute to the association between aMed scores, lower abdominal adipose tissue, and inflammation.

Subtype-specific Body Composition and Metabolic Risk in Patients With Primary Aldosteronism.

BACKGROUND: Primary aldosteronism (PA) is associated with increased metabolic risks. However, controversy exists as to which subtype of PA has a higher metabolic risk between bilateral and lateralized PA. This study aimed to assess the body composition of 2 PA subtypes, bilateral PA and lateralized PA, according to sex and autonomous cortisol secretion (ACS) and their contribution to comorbidities. DESIGN AND METHODS: A total of 400 patients with PA (females, n = 210) and 1:10 age- and sex-matched healthy controls (n = 4000) were enrolled. The skeletal muscle area (SMA), subcutaneous fat area, and visceral fat area (VFA) at the third lumbar spine were calculated using abdominal computed tomography-based body composition analysis. RESULTS: Patients with bilateral PA had higher body mass index (BMI) in both sexes (all P < .05). Hemoglobin A1c level and the prevalence of diabetes were higher in female patients with bilateral PA than in those with lateralized PA (all P < .05). The VFA/BMI ratio was significantly higher in bilateral PA patients than in lateralized PA patients (5.77 ± 2.69 vs 4.56 ± 2.35 in men; 4.03 ± 2.58 vs 2.53 ± 2.05 in women, all P < .001). PA patients with ACS showed decreased SMA compared to those without ACS. Compared with healthy controls, all patients with bilateral PA and female patients with lateralized PA showed significantly higher VFA and VFA/BMI. CONCLUSIONS: Patients with bilateral PA were more obese and had higher VFA levels than those with lateralized PA. Despite a milder form of PA, this metabolically unfavorable visceral fat distribution may lead to a higher metabolic risk in patients with bilateral PA.

Impact of Liver Transplantation on Adipose Tissue Compartments and Its Association With Metabolic Sequela.

BACKGROUND: Loss of skeletal muscle can be accompanied by an increase in adipose tissue leading to sarcopenic obesity. There are limited data on how liver transplantation (LT) might impact adipose tissue compartments, particularly among patients with metabolically active disease, such as nonalcoholic steatohepatitis (NASH) and subsequent metabolic sequela. METHODS: Skeletal muscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured using cross-sectional imaging performed in 190 patients pre-LT, 6 mo post-LT and 12 mo post-LT. Changes in adipose tissue and their impact on metabolic diseases were determined in patients transplanted for NASH versus non-NASH. RESULTS: Skeletal muscle, VAT, and SAT were similar in patients with NASH and non-NASH pre-LT despite a higher burden of metabolic diseases in patients with NASH. Following LT, no significant differences between skeletal muscle and SAT were observed in the entire cohort and among patients with NASH (versus non-NASH). LT recipients with the highest muscle mass pre-LT were at the greatest risk for muscle loss post-LT. A time-dependent increase in VAT was noted post-LT, which was more robust among patients with a history of NASH cirrhosis. In adjusted multivariate analysis, NASH versus non-NASH was a strong predictor of post-LT increase in VAT (ß-coefficient 3.00, P = 0.04). Pre-LT VAT was an independent predictor of post-LT serum triglycerides (ß-coefficient 5.49 ± 2.78, P = 0.05) and low-density lipoprotein cholesterol (ß-coefficient 1.80 ± 0.75, P = 0.02). A trend between pre-LT VAT and diabetes was noted but did not reach statistical significance. CONCLUSIONS: VAT but not SAT increases rapidly after LT, especially among patients transplanted for NASH cirrhosis and predicts future metabolic burden.

Association of visceral fat area or BMI with arterial stiffness in ideal cardiovascular health metrics among T2DM patients.

BACKGROUND: "Obesity paradox" occurs in type 2 diabetes mellitus (T2DM) patients when body mass index (BMI) is applied to define obesity. We examined the association of visceral fat area (VFA) as an obesity measurement with arterial stiffness in seven ideal cardiovascular health metrics (ICVHMs). METHODS: A total of 29 048 patients were included in the analysis from June 2017 to April 2021 in 10 sites of National Metabolic Management Centers. ICVHMs were modified from the recommendations of the American Heart Association. Brachial-ankle pulse wave velocity (BaPWV) ≥ 1400 cm/s was employed to evaluate increased arterial stiffness. Multivariate regression models were used to compare the different effects of BMI and VFA on arterial stiffness. RESULTS: Lower VFA was more strongly associated with low BaPWV than lower BMI when other ICVHMs were included (adjusted odds ratio [OR], 0.85 [95% confidence interval [CI], 0.80-0.90] vs OR 1.08 [95% CI, 1.00-1.17]). Multivariable-adjusted ORs for arterial stiffness were highest in patients with the VAT area VFA in the range of 150-200 cm2 (adjusted OR, 1.26 [95% CI 1.12-1.41]). Compared with participants with VAT VFA < 100 cm2 , among participants with higher VAT VFA, the OR for arterial stiffness decreased gradually from 1.89 (95% CI, 1.73-2.07) in patients who had ≤1 ICVHM to 0.39 (95% CI, 0.25-0.62) in patients who had ≥5 ICVHMs. CONCLUSION: In patients with T2DM, using VAT for anthropometric measures of obesity, VFA was more relevant to cardiovascular risk than BMI in the seven ICVHMs. For anthropometric measures of obesity in the ICVHMs to describe cardiovascular risk VFA would be more optimal than BMI.

Circulating miRNAs Detect High vs Low Visceral Adipose Tissue Inflammation in Patients Living With Obesity.

CONTEXT: The severity of visceral adipose tissue (VAT) inflammation in individuals with obesity is thought to signify obesity subphenotype(s) associated with higher cardiometabolic risk. Yet, this tissue is not accessible for direct sampling in the nonsurgical patient. OBJECTIVE: We hypothesized that circulating miRNAs (circ-miRs) could serve as biomarkers to distinguish human obesity subgroups with high or low extent of VAT inflammation. METHODS: Discovery and validation cohorts of patients living with obesity undergoing bariatric surgery (n = 35 and 51, respectively) were included. VAT inflammation was classified into low/high based on an expression score derived from the messenger RNA levels of TNFA, IL6, and CCL2 (determined by reverse transcription polymerase chain reaction). Differentially expressed circ-miRs were identified, and their discriminative power to detect low/high VAT inflammation was assessed by receiver operating characteristic-area under the curve (ROC-AUC) analysis. RESULTS: Fifty three out of 263 circ-miRs (20%) were associated with high-VAT inflammation according to Mann-Whitney analysis in the discovery cohort. Of those, 12 (12/53 = 23%) were differentially expressed according to Deseq2, and 6 significantly discriminated between high- and low-VAT inflammation with ROC-AUC greater than 0.8. Of the resulting 5 circ-miRs that were differentially abundant in all 3 statistical approaches, 3 were unaffected by hemolysis and validated in an independent cohort. Circ-miRs 181b-5p, 1306-3p, and 3138 combined with homeostatic model assessment of insulin resistance (HOMA-IR) exhibited ROC-AUC of 0.951 (95% CI, 0.865-1) and 0.808 (95% CI, 0.654-0.963) in the discovery and validation cohorts, respectively, providing strong discriminative power between participants with low- vs high-VAT inflammation. Predicted target genes of these miRNAs are enriched in pathways of insulin and inflammatory signaling, circadian entrainment, and cellular senescence. CONCLUSION: Circ-miRs that identify patients with low- vs high-VAT inflammation constitute a putative tool to improve personalized care of patients with obesity.

Skewness in Body fat Distribution Pattern Links to Specific Cardiometabolic Disease Risk Profiles.

OBJECTIVE: Fat distribution pattern could help determine cardiometabolic risk profile. This study aimed to evaluate the association of balance/imbalance between visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and liver fat (LF) with incident type 2 diabetes (T2D) and cardiovascular disease (CVD) in the UK Biobank prospective cohort study. METHODS: Magnetic resonance images of 40 174 participants were analyzed for VAT, aSAT, and LF using AMRA® Researcher. To assess fat distribution patterns independent of body mass index (BMI), fat z-scores (z-VAT, z-aSAT, z-LF) were calculated. Participants without prevalent T2D/CVD (N = 35 138) were partitioned based on balance between (1) z-VAT and z-LF (z-scores = 0 as cut-points for high/low), (2) z-VAT and z-aSAT, and (3) z-LF and z-aSAT. Associations with T2D/CVD were investigated using Cox regression (crude and adjusted for sex, age, BMI, lifestyle, arterial hypertension, statin treatment). RESULTS: T2D was significantly associated with z-LF (hazard ratio, [95% CI] 1.74 [1.52-1.98], P < .001) and z-VAT (1.70 [1.49-1.95], P < .001). Both remained significant after full adjustment. For z-scores balance, strongest associations with T2D were z-VAT > 0 and z-LF > 0 (4.61 [2.98-7.12]), z-VAT > 0 and z-aSAT < 0 (4.48 [2.85-7.06]), and z-LF > 0 and z-aSAT < 0 (2.69 [1.76-4.12]), all P < .001. CVD was most strongly associated with z-VAT (1.22 [1.16-1.28], P < .001) which remained significant after adjustment for sex, age, BMI, and lifestyle. For z-scores balance, strongest associations with CVD were z-VAT > 0 and z-LF < 0 (1.53 [1.34-1.76], P < .001) and z-VAT > 0 and z-aSAT < 0 (1.54 [1.34-1.76], P < .001). When adjusted for sex, age, and BMI, only z-VAT > 0 and z-LF < 0 remained significant. CONCLUSION: High VAT in relation to BMI (z-VAT > 0) was consistently linked to both T2D and CVD; z-LF > 0 was linked to T2D only. Skewed fat distribution patterns showed elevated risk for CVD (z-VAT > 0 and z-LF < 0 and z-VAT > 0 and z-aSAT < 0) and T2D (z-VAT > 0 and z-aSAT < 0).