BACKGROUND: Cardiovascular diseases (CVDs) are the primary cause of mortality globally. The prevalence of obesity is rising worldwide; there seems to be a significant positive association between obesity and CVDs. The distribution of fat in the abdominal area in the form of visceral (VAT) or subcutaneous adipose tissue (SAT) affects the risk of CVDs. The aim of the present study was to conduct a systematic review of the available literature regarding the association between the VAT-to-SAT ratio and CVDs.
METHODS: A comprehensive search strategy was used to retrieve all human observational studies indexed in PubMed, Scopus and Google Scholar databases/search engines (from Jan 2000 up to Oct 2023). The VAT-to-SAT or SAT-to-VAT ratio was an independent variable and various cardiovascular diseases, including hypertension, atherosclerosis, coronary heart disease, cerebrovascular disease and heart failure, were considered as outcomes of interest.
RESULTS: Out of 1173 initial studies, 910 papers were screened. Based on the inclusion criteria, 883 papers were excluded. Finally, 27 papers (18 cross-sectional and 9 cohort studies) published between 2010 and 2023 which met the inclusion criteria were reviewed.
CONCLUSIONS: The distribution of abdominal fat seems to be associated with the risk of CVDs; the majority of the evidence suggests that a higher abdominal VAT-to-SAT ratio is associated with the development of CVDs. Therefore, this ratio can be used as a prognostic indicator for CVDs.
BACKGROUND: Not applicable.

Abdominal subcutaneous fat deposition (ASFD) is not only related to meat quality in the pig industry but also to human health in medicine. It is of great value to elucidate the potential molecular mechanisms of ASFD. The present study aims to identify obese-specific biomarkers and key pathways correlated with ASFD in pigs. The ASF-related mRNA expression dataset GSE136754 was retrieved from the Gene Expression Omnibus (GEO) database and systematically analyzed using a comprehensive bioinformatics method. A total of 565 differentially expressed genes (DEGs) were identified between three obese and three lean pigs, and these DEGs were mainly involved in the p53 signaling pathway, MAPK signaling pathway and fatty acid metabolism. A protein-protein interaction (PPI) network, consisting of 540 nodes and 1,065 edges, was constructed, and the top ten genes with the highest degree scores-ABL1, HDAC1, CDC42, HDAC2, MRPS5, MRPS10, MDM2, JUP, RPL7L1 and UQCRFS1-were identified as hub genes in the whole PPI network. Especially HDAC1, MDM2, MRPS10 and RPL7L1 were identified as potential robust obese-specific biomarkers due to their significant differences in single gene expression levels and high ROC area; this was further verified by quantitative real-time PCR (qRT-PCR) on abdominal subcutaneous fat samples from obese-type (Saba) and lean-type (Large White) pigs. Additionally, a mRNA-miRNA-lncRNA ceRNA network consisting of four potential biomarkers, 15 miRNAs and 51 lncRNAs was established, and two targeted lncRNAs with more connections, XIST and NEAT1, were identified as potentially important regulatory factors. The findings of this study may provide novel insights into the molecular mechanism involved in ASFD.

Abdominal fat is increasingly linked to brain health. A total of 10,001 healthy participants were scanned on 1.5T MRI with a short whole-body MR imaging protocol. Deep learning with FastSurfer segmented 96 brain regions. Separate models segmented visceral and subcutaneous abdominal fat. Regression analyses of abdominal fat types and normalized brain volumes were evaluated, controlling for age and sex. Logistic regression models determined the risk of brain total gray and white matter volume loss from the highest quartile of visceral fat and lowest quartile of these brain volumes. This cohort had an average age of 52.9 ± 13.1 years with 52.8% men and 47.2% women. Segmented visceral abdominal fat predicted lower volumes in multiple regions including: total gray matter volume (r = -.44, p<.001), total white matter volume (r =-.41, p<.001), hippocampus (r = -.39, p< .001), frontal cortex (r = -.42, p<.001), temporal lobes (r = -.44, p<.001), parietal lobes (r = -.39, p<.001), occipital lobes (r =-.37, p<.001). Women showed lower brain volumes than men related to increased visceral fat. Visceral fat predicted increased risk for lower total gray matter (age 20-39: OR = 5.9; age 40-59, OR = 5.4; 60-80, OR = 5.1) and low white matter volume: (age 20-39: OR = 3.78; age 40-59, OR = 4.4; 60-80, OR = 5.1). Higher subcutaneous fat is related to brain volume loss. Elevated visceral and subcutaneous fat predicted lower brain volumes and may represent novel modifiable factors in determining brain health.

In this study, we have compared frequencies, phenotype, function and metabolic requirements of B cells isolated from the breast and abdominal subcutaneous adipose tissue (AT) of women with obesity who underwent weight reduction surgeries. Results show that B cells from the abdominal AT are more inflammatory than those from the breast, characterized by higher frequencies of inflammatory B cell subsets and higher expression of RNA for inflammatory markers associated with senescence. Secretion of autoimmune antibodies is also higher in the abdominal AT as compared to the breast, and is associated with higher frequencies of autoimmune B cells with the membrane phenotype CD21lowCD95+ B cells expressing the transcription factor T-bet. Moreover, glucose uptake is higher in B cells from the abdominal AT as compared to the breast, thereby suggesting a better capacity to perform glycolysis, needed to support intrinsic B cell inflammation and autoimmune antibody secretion.

Adipose tissue (AT) inflammation predisposes to insulin resistance and metabolic syndrome in obesity.
To investigate the association between adipocyte size, AT inflammation, systemic inflammation, and metabolic and atherosclerotic complications of obesity in a sex-specific manner.
Cross-sectional cohort study.
University hospital in the Netherlands.
A total of 302 adult subjects with a body mass index (BMI) ≥ 27 kg/m2.
We obtained subcutaneous abdominal fat biopsies and systematically assessed, in a sex-specific manner, associations of several parameters of AT inflammation (including adipocyte size, macrophage content, crown-like structures, and gene expression) to biomarkers of systemic inflammation, leukocyte number and function, and to the presence of metabolic syndrome, insulin resistance, and carotid atherosclerotic plaques, assessed with ultrasound.
Adipocyte size was associated with metabolic syndrome and AT macrophage content with insulin resistance. In contrast, none of the AT parameters was associated with carotid atherosclerosis, although mRNA expression of the anti-inflammatory IL-37 was associated with a lower intima-media thickness. We revealed profound sex-specific differences, with an association between BMI and adipocyte size, and between adipocyte size and metabolic syndrome in men only. Also, only men showed an association between adipocyte size, AT expression of leptin and MCP-1, and AT macrophage numbers, and between AT inflammation (crown-like structure number) and several circulating inflammatory proteins, including high specificity C-reactive protein, and IL-6.
Inflammation in abdominal subcutaneous adipose tissue is more related to the metabolic than the atherosclerotic complications of obesity, and there are profound sex-specific differences in the association between BMI, adipocyte size, AT inflammation, and systemic inflammation, which are much stronger in men than women.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that often coexists with a metabolic disorder. Studies have demonstrated that the malfunction of adipose tissue, particularly abdominal adipose tissue, could exacerbate reproductive and metabolic problems in PCOS patients. Adipose tissue-secreted signaling mediators (e.g., lipids and metabolites) would then interact with other body organs, including the ovary, to maintain the systemic equilibrium.
In this study, we examined adipose samples from PCOS patients and unaffected individuals using a liquid chromatography-mass spectrometry-based metabonomics approach (LC-MS/MS). PCOS biomarkers were selected using multivariate statistical analysis.
Our pathway analysis revealed that these differential metabolites could be engaged in inflammatory diseases and mitochondrial beta-oxidation. We further developed an in vitro PCOS cell model to examine the effects of hyperandrogenism on granulosa cells and related metabolic disorders. We noted that isoleucine recovered the promotive effect on cell apoptosis, inhibitory effect on cell proliferation, sex hormone secretion, and mitochondrial function induced by dehydroepiandrosterone. Our gas chromatography-mass spectrometry targeted analysis (GC-MS/MS) revealed that isoleucine was significantly decreased in PCOS patients.
Based on these results, we speculate that metabolome alterations are vital in ameliorating PCOS symptoms. This may be a novel therapeutic target for PCOS treatment. Our study provides preliminary evidence that these findings will enhance our ability to accurately diagnose and intervene in PCOS.

Effective storage of excess energy in abdominal subcutaneous adipose tissue during periods of overeating may help attenuate weight-gain-related insulin resistance. The objective of this study was to assess changes in the expression of factors regulating abdominal subcutaneous adipose tissue storage capacity in response to a brief exposure to overeating in nonobese adults. Because exercise can alter the expression of genes involved in regulating adipose tissue storage capacity, we compared the responses to overeating in regular exercisers (EX, n = 11) and nonexercisers (nonEX, n = 11). Abdominal subcutaneous adipose tissue samples and oral glucose tolerance tests were performed before and after participants ate 30% above their estimated daily energy requirements for 1 week. Both EX and nonEX gained ∼1 kg (P < 0.01), and Matsuda insulin sensitivity index was reduced ∼15% (P = 0.04) in both groups. Gene expression of factors involved in lipid metabolism (HSL, ATGL, DGAT, and PPARγ) and angiogenesis (HIF1α and KDR) were increased (P < 0.05), with no differences observed between EX and nonEX. In contrast, protein abundance of these factors did not change. The modest overeating stimulus did not increase markers of inflammation in the systemic circulation or adipose tissue. Overall, our findings indicate that a brief and modest overeating stimulus can impair insulin sensitivity and upregulate genes involved in abdominal adipose tissue storage capacity similarly in exercisers and nonexercisers. ClinicalTrials.gov ID#: NCT02701738.

Higher levels of intra-abdominal adipose tissue (IAAT) comprising visceral adipose tissue (VAT), intermuscular adipose tissue (IMAT), and liver fat are posited drivers of obesity-related chronic disease risk. Fast food is hypothesized to contribute to IAAT patterns.
We quantified levels of abdominal subcutaneous adipose tissue (SAT), IAAT, and odds of metabolic-associated fatty liver disease (MAFLD) in middle age according to average fast-food intake over the preceding 25 y.
We analyzed data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants underwent 6 clinical exams and measurements over 25 y with computed tomography-measured VAT, SAT, and IMAT (n = 3156), plus MAFLD defined by liver attenuation (≤40 Hounsfield units) and 1 metabolic abnormality at year 25 (2010, n = 3001, n cases = 302). We estimated means of VAT, SAT, IMAT, and liver attenuation at the year 25 exam according to categories of average fast-food intake over the previous 25 y adjusted for sociodemographic and lifestyle factors and logistic regression to estimate the odds ratio of MAFLD at year 25.
With higher average fast-food intake over 25 y (categorized as follows: never-1×/mo, >1×-3×/mo, 1-<2×/wk, 2-<3×/wk, ≥3×/wk), there were monotonic higher levels of VAT (98.5, 127.6, 134.5, 142.0, 145.5 cm3), P-trend < 0.0001, which were consistent across anthropometrically classified obesity categories. There was a similar pattern with liver fat. There were higher levels of IMAT and SAT with higher fast-food intake (P-trend = 0.003, 0.0002, respectively), with amounts leveling off at ≥2×/wk. In addition, compared with participants who ate fast food never-1×/mo, there were monotonic higher odds of having MAFLD at year 25 with higher average fast-food intake, with participants who ate fast food ≥3×/wk having an OR of MAFLD = 5.18 (95% CI: 2.87, 9.37).
There were monotonic higher levels of VAT, liver fat, and odds of having MAFLD in middle age according to higher average fast-food intake over the preceding 25 y.

Fat redistribution from subcutaneous adipose tissue (SAT) to the abdominal viscera, pericardium, liver, and skeletal muscle contributes to the rising burden of cardiometabolic disease among persons with HIV (PWH). Previous studies found SAT inflammation in PWH impairs lipid storage and persists despite plasma viral suppression on antiretroviral therapy (ART). In this study, we identified SAT immune-related genes associated with ectopic fat deposition in PWH on long-term ART.
A total of 92 PWH with well-controlled viremia underwent computed tomography imaging and abdominal SAT biopsy for gene expression analysis. SAT gene expression was measured using a NanoString panel of 255 immune-related genes. Associations between gene expression and computed tomography measurements of the volume and attenuation (radiodensity) of metabolically relevant ectopic fat depots were assessed using multivariable linear regression and network analysis.
Greater SAT volume was associated with higher visceral and pericardial adipose tissue volume, but lower skeletal muscle attenuation. Lower SAT attenuation, a measure of lipid content, was associated with lower visceral adipose tissue attenuation. Hierarchical clustering identified a subset of macrophage-related genes in SAT, including CCL2, CCL22, CCL13, CCR1, CD86, CD163, IL-6, IL-10, MRC1, and TREM2, which were associated with an increased lipid deposition in multiple ectopic depots.
Altered expression of macrophage-related genes in SAT is associated with differences in ectopic fat depot morphometrics among PWH on long-term ART, including in the pericardial and visceral compartments. These findings provide basis for future studies to assess host, virus, and treatment factors shaping the SAT immune environment and its effects on morphometric changes and metabolic comorbidities in PWH.

This study investigated whether variations in cell death-inducing DNA fragmentation factor alpha subunit-like effector A (CIDEA) mRNA expression and protein levels are modulated by the pattern of abdominal fat distribution in adolescent girls with obesity.
This study recruited 35 adolescent girls with obesity and characterized their abdominal fat distribution by magnetic resonance imaging. Participants had only a periumbilical/abdominal (n = 14) or a paired abdominal and gluteal subcutaneous adipose tissue (SAT) biopsy (n = 21). CIDEA expression was determined by reverse transcription-polymerase chain reaction, CIDEA protein level by Western blot, and the turnover of adipose lipids and adipocytes by 2 H2 O labeling. In six girls, a second abdominal SAT biopsy was performed (after ~34.2 months) to explore the weight gain effect on CIDEA expression in abdominal SAT.
CIDEA expression decreased in abdominal SAT from participants with high visceral adipose tissue (VAT)/(VAT+SAT); CIDEA inversely correlated with number of small adipocytes, with the increase in preadipocyte proliferation, and with adipogenesis. A strong inverse correlation was found between CIDEA protein level with the newly synthetized glycerol (r = -0.839, p = 0.0047). Following weight gain, an increase in adipocytes\' cell diameter with a decrease in CIDEA expression and RNA-sequencing transcriptomic profile typical of adipocyte dysfunction was observed.
Reduced expression of CIDEA in girls with high VAT/(VAT+SAT) is associated with adipocyte hypertrophy and insulin resistance.