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Assessing the Contribution of Relative Macrophage Frequencies to Subcutaneous Adipose Tissue.

ABSTRACT: Background: Macrophages play an important role in regulating adipose tissue function, while their frequencies in adipose tissue vary between individuals. Adipose tissue infiltration by high frequencies of macrophages has been linked to changes in adipokine levels and low-grade inflammation, frequently associated with the progression of obesity. The objective of this project was to assess the contribution of relative macrophage frequencies to the overall subcutaneous adipose tissue gene expression using publicly available datasets. Methods: Seven publicly available microarray gene expression datasets from human subcutaneous adipose tissue biopsies (n = 519) were used together with TissueDecoder to determine the adipose tissue cell-type composition of each sample. We divided the subjects in four groups based on their relative macrophage frequencies. Differential gene expression analysis between the high and low relative macrophage frequencies groups was performed, adjusting for sex and study. Finally, biological processes were identified using pathway enrichment and network analysis. Results: We observed lower frequencies of adipocytes and higher frequencies of adipose stem cells in individuals characterized by high macrophage frequencies. We additionally studied whether, within subcutaneous adipose tissue, interindividual differences in the relative frequencies of macrophages were reflected in transcriptional differences in metabolic and inflammatory pathways. Adipose tissue of individuals with high macrophage frequencies had a higher expression of genes involved in complement activation, chemotaxis, focal adhesion, and oxidative stress. Similarly, we observed a lower expression of genes involved in lipid metabolism, fatty acid synthesis, and oxidation and mitochondrial respiration. Conclusion: We present an approach that combines publicly available subcutaneous adipose tissue gene expression datasets with a deconvolution algorithm to calculate subcutaneous adipose tissue cell-type composition. The results showed the expected increased inflammation gene expression profile accompanied by decreased gene expression in pathways related to lipid metabolism and mitochondrial respiration in subcutaneous adipose tissue in individuals characterized by high macrophage frequencies. This approach demonstrates the hidden strength of reusing publicly available data to gain cell-type-specific insights into adipose tissue function.

SUBMITTER: Kalafati M

PROVIDER: S-EPMC8200404 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeThis study compared subcutaneous adipose tissue (SAT) measurements using a skinfold caliper and Renco Lean-Meater Series 12 A-mode portable ultrasound scanner (A-US). It aimed to assess their inter- and intra-rater reliability and measure the agreement between both methods.MethodsEighty-four volunteers of different fitness levels were divided into three groups by Ʃ6 skinfolds: G1 ≤ 55 mm (n = 33 males); G2 > 55 mm (n = 32 males); G3 = 98.0 ± 52.3 mm (n = 19 females). Triceps, subscapular, biceps, iliac crest, supraspinal, abdominal, front thigh and medial calf were assessed by ultrasound and skinfolds. Two technicians for both tools performed triplicate measures. Intraclass correlation (ICC), technical error of measurement (TEM) and coefficients of variation (CVs) were applied for test-retest and inter-rater reliability. Non-Parametric statistics were used in order to establish possible statistical differences and correlation between skinfolds thickness and uncompressed subcutaneous adipose tissue thickness from ultrasound. The amount of agreement between both methods was assessed with Lin's coefficient and a scatterplot of all site locations. A Bland-Altman plot was constructed to establish limits of agreement between groups and regression analysis was employed to assess the ability of skinfolds to explain the variance of ultrasound.ResultsTest-retest ICC for skinfolds and ultrasound were higher than 0.989 and 0.793, respectively. Inter-rater ICC for skinfolds was 0.999 with a 95% CI of 0.995 to 0.999 and for ultrasound was 0.755 with a much larger 95% CI of 0.622 to 0.841. TEMs (> 8.50%) and CVs (> 6.72%) compromised ultrasound reliability. Statistical differences were found in most of the analysed anatomical sites (p < 0.001) except in biceps G2 (Z = -1.150, p = 0.25) and G3 (Z = -1.309, p = 0.19). Good correlations (r > 0.7, p ≤ 0.05) were reported at almost all anatomical sites and groups except for biceps (G1: Rho = 0.26, p = 0.140) and abdominal (G2: Rho = -0.16, p = 0.38; G3: Rho = 0.43, p = 0.068). Lin's concordance correlation coefficient registered low values of agreement between skinfolds and A-mode ultrasound (ranged from-0.009-0.646). The scatterplot and the estimated regression line drawn through the midst of all anatomical sites of the whole sample had a slope of 0.51 and R2 adjusted = 0.62 was obtained. The combined analysis between the Bland-Altman plot and the linear regression showed that specifically in the G2 and G3 groups, as the SAT increases the differences between skinfolds and ultrasounds measurements also increases.ConclusionsThe Renco Lean-Meater ultrasound is not interchangeable with skinfold measures. Its utility is questionable, particularly for assessing SAT in active adult populations. Its poor test-retest and inter-rater reliability as well as the lack of agreement when compared to the skinfolds would exclude the free use of the A-mode ultrasound scanner in its hypothetical replacing of the classical calipers.

Project description:Obesity is a complex multifactorial phenotype that influences several metabolic pathways. Yet, few studies have examined the relations of different body fat compartments to urinary and serum metabolites. Anthropometric phenotypes (visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), the ratio between VAT and SAT (VSR), body mass index (BMI), waist circumference (WC)) and urinary and serum metabolite concentrations measured by nuclear magnetic resonance spectroscopy were measured in a population-based sample of 228 healthy adults. Multivariable linear and logistic regression models, corrected for multiple testing using the false discovery rate, were used to associate anthropometric phenotypes with metabolites. We adjusted for potential confounding variables: age, sex, smoking, physical activity, menopausal status, estimated glomerular filtration rate (eGFR), urinary glucose, and fasting status. In a fully adjusted logistic regression model dichotomized for the absence or presence of quantifiable metabolite amounts, VAT, BMI and WC were inversely related to urinary choline (ß = -0.18, p = 2.73*10-3), glycolic acid (ß = -0.20, 0.02), and guanidinoacetic acid (ß = -0.12, p = 0.04), and positively related to ethanolamine (ß = 0.18, p = 0.02) and dimethylamine (ß = 0.32, p = 0.02). BMI and WC were additionally inversely related to urinary glutamine and lactic acid. Moreover, WC was inversely associated with the detection of serine. VAT, but none of the other anthropometric parameters, was related to serum essential amino acids, such as valine, isoleucine, and phenylalanine among men. Compared to other adiposity measures, VAT demonstrated the strongest and most significant relations to urinary and serum metabolites. The distinct relations of VAT, SAT, VSR, BMI, and WC to metabolites emphasize the importance of accurately differentiating between body fat compartments when evaluating the potential role of metabolic regulation in the development of obesity-related diseases, such as insulin resistance, type 2 diabetes, and cardiovascular disease.

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Assessing the Contribution of Relative Macrophage Frequencies to Subcutaneous Adipose Tissue.

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