Visceral adipose tissue but not subcutaneous adipose tissue is associated with urine and serum metabolites

Abstract

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.

Lifestyle‐Intervention‐Induced Reduction of Abdominal Fat Is Reflected by a Decreased Circulating Glycerol Level and an Increased HDL Diameter

“…The association of circulating metabolic biomarkers with abdominal fat has been frequently observed in previous studies. [ 5,29,30 ] We now showed in older adults, that after adjusting for BMI, glycerol particularly associated with abdominal fat measures. Glycerol is produced by white adipose tissue to dispose of excess glucose [ 31 ] leading, via hepatic gluconeogenesis, to an increase in circulating glucose levels.…”

Adipokines and Adipose Tissue-Related Metabolites, Nuts and Cardiovascular Disease

“…Adiposity indexes and WAT compartments have been associated with urinary metabolites involved in gut microbiota metabolism [155], such as choline (its metabolism by the gut microbiota results in the production of TMA, which upon absorption by the host is converted in the liver to trimethylamine-N-oxide [TMAO]) [156,157], ethanolamine (its utilization by certain gut bacteria affects lipid metabolism and SCFA biosynthesis [158], dimethylamine [159] and glutamine [160].…”

Developmentally Driven Changes in Adipogenesis in Different Fat Depots Are Related to Obesity

“…We analyzed the expression of the top 34 genes showing most divergent expression dynamics during adipogenesis in epi vs. ing cell lines in human vis and sc AT. Nine out of the 34 hits in epi/ing mouse cell lines do not present orthologs in primates or humans and/or were not present on the mRNA chips: Gm4955; Gm24598; NONMMUT00716 [3][4][5]; NONMMUT01574 [5][6][7]; 9930111J21Rik [1][2]; Tgtp2, KnowTID_00007994; Tnfrsf26. Moreover, LHX8 and Gbp6 were not expressed in human AT at all.…”

“…However, obesity itself does not necessarily lead to these comorbidities (3), although adipose tissue (AT) distribution may contribute to cardio-metabolic diseases even in lean individuals (4). It is well-established that fat stored in visceral (vis) depots makes individuals more prone to metabolic complications than subcutaneous (sc) fat (5)(6)(7).…”