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Differences emerge in visceral adipose tissue accumulation after selection for innate cardiovascular fitness.

ABSTRACT: Cardiorespiratory fitness (CRF) has been reported to be inversely associated with visceral adipose tissue (VAT) accumulation, independent of body weight. However, the confounding effect of physical activity on the association between CRF and VAT remains inadequately addressed. On the basis of maximal oxygen uptake (VO(2 max)), 143 sedentary, overweight women were dichotomized into high-fit (HF) and low-fit (LF) groups. Body composition and VAT were measured using dual-energy X-ray absorptiometry and computed tomography, respectively, and activity-related energy expenditure (AEE) was calculated using the doubly labeled water technique. No differences were observed between HF and LF for body mass index (HF 28.2 ± 1.3; LF 28.3 ± 1.31 kg m(-2)), total body weight (HF 77.5 ± 6.8; LF 77.9 ± 7.3 kg), total fat mass (HF 33.5 ± 5.1; LF 33.9 ± 4.4 kg) or AEE (HF 439.9 ± 375.4; LF 517.9 ± 298.7 kcal day(-1)). Significant differences in visceral adiposity (HF 68.5 ± 30.4; LF 91.2 ± 31.8 cm(2); P<0.001) and insulin sensitivity (HF 5.1 ± 1.8; LF 3.1 ± 2.4 S(I) × 10(-4) min(-1) ?IU(-1) ml(-1); P<0.01) were observed between the HF and LF groups, independent of age, race and AEE. This study affirms previous findings that CRF is an important determinant of the accumulation of VAT, and this relationship is independent of physical activity.

SUBMITTER: Brock DW

PROVIDER: S-EPMC2982865 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Differences emerge in visceral adipose tissue accumulation after selection for innate cardiovascular fitness.

Brock D W DW Irving B A BA Gower B B Hunter G R GR

International journal of obesity (2005) 20100720 2

Cardiorespiratory fitness (CRF) has been reported to be inversely associated with visceral adipose tissue (VAT) accumulation, independent of body weight. However, the confounding effect of physical activity on the association between CRF and VAT remains inadequately addressed. On the basis of maximal oxygen uptake (VO(2 max)), 143 sedentary, overweight women were dichotomized into high-fit (HF) and low-fit (LF) groups. Body composition and VAT were measured using dual-energy X-ray absorptiometry ...[more]

PMID: 20644556

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Project description:OBJECTIVE:Macrophages are important producers of obesity-induced MCP-1; however, initial obesity-induced increases in MCP-1 production precede M1 macrophage accumulation in visceral adipose tissue (VAT). The initial cellular source of obesity-induced MCP-1 in vivo is currently unknown. Preliminary reports based on in vitro studies of preadipocyte cell lines and adherent stroma-vascular fraction cells suggest that resident stromal cells express MCP-1. In the past several years, elegant methods of identifying adipocyte progenitor cells (AdPCs) have become available, making it possible to study these cells in vivo. We have previously published that global deletion of transcription factor Inhibitor of Differentiation 3 (Id3) attenuates high fat diet-induced obesity, but it is unclear if Id3 plays a role in diet-induced MCP-1 production. We sought to determine the initial cellular source of MCP-1 and identify molecular regulators mediating MCP-1 production. METHODS:Id3 (+/+) and Id3 (-/-) mice were fed either a standard chow or HFD for varying lengths of time. Flow cytometry, semi-quantitative real-time PCR, ELISAs and adoptive transfers were used to assess the importance of AdPCs during diet-induced obesity. Flow cytometry was also performed on a cohort of 14 patients undergoing bariatric surgery. RESULTS:Flow cytometry identified committed CD45(-)CD31 (-) Ter119(-)CD29(+)CD34(+)Sca-1(+)CD24(-) adipocyte progenitor cells as producers of high levels of MCP-1 in VAT. High-fat diet increased AdPC numbers, an effect dependent on Id3. Loss of Id3 increased p21(Cip1) levels and attenuated AdPC proliferation, resulting in reduced MCP-1 and M1 macrophage accumulation in VAT, compared to Id3 (+/+) littermate controls. AdPC rescue by adoptive transfer of 50,000 Id3 (+/+) AdPCs into Id3 (-/-) recipient mice increased MCP-1 levels and M1 macrophage number in VAT. Additionally, flow cytometry identified MCP-1-producing CD45(-)CD31(-)CD34(+)CD44(+)CD90(+) AdPCs in human omental and subcutaneous adipose tissue, with a higher percentage in omental adipose. Furthermore, high surface expression of CD44 marked abundant MCP-1 producers, only in visceral adipose tissue. CONCLUSIONS:This study provides the first in vivo evidence, to our knowledge, that committed AdPCs in VAT are the initial source of obesity-induced MCP-1 and identifies the helix-loop-helix transcription factor Id3 as a critical regulator of p21(Cip1) expression, AdPC proliferation, MCP-1 expression and M1 macrophage accumulation in VAT. Inhibition of Id3 and AdPC expansion, as well as CD44 expression in human AdPCs, may serve as unique therapeutic targets for the regulation of adipose tissue inflammation.

Project description:Visceral adipose tissue (VAT) is a main site where metabolic and immunologic processes interplay to regulate, at local and systemic level, the inflammatory status and immune response. Obesity-associated inflammation and immune dysfunctions are inextricably linked to tumor but, in spite of intense efforts, the mechanisms underpinning this association remain elusive. In this report, we characterized the profile of VAT-associated and circulating innate lymphocyte and regulatory T (Treg) cell subsets underlying inflammatory conditions, such as obesity and colorectal cancer (CRC). Analysis of NK, NKT-like, ?? T, and Treg cell populations in VAT and blood of healthy lean subjects revealed that CD56hi NK and OX40+ Treg cells are more abundant in VAT with respect to blood. Conversely, CD56dim NK and total Treg cells are most present in the circulation, while ?? T lymphocytes are uniformly distributed in the two compartments. Interestingly, a reduced frequency of circulating activated Treg cells, and a concomitant preferential enrichment of OX40-expressing Treg cells in VAT, were selectively observed in obese (Ob) subjects, and directly correlated with body mass index. Likewise, CRC patients were characterized by a specific enrichment of VAT-associated NKT-like cells. In addition, Ob and CRC-affected individuals shared a significant reduction of the V?9V?2/?? T cell ratio at systemic level. The alterations in the relative proportions of Treg and NKT-like cells in VAT were found to correlate with the content of pro- and anti-inflammatory polyunsaturated fatty acids (PUFA), respectively. Overall, these results provide evidence for distinct alterations of the immune cell repertoire in the periphery with respect to the VAT microenvironment that uniquely characterize or are shared by different inflammatory conditions, such as obesity and CRC, and suggest that VAT PUFA composition may represent one of the factors that contribute to shape the immune phenotypes.

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.

Dataset Information

Differences emerge in visceral adipose tissue accumulation after selection for innate cardiovascular fitness.

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Differences emerge in visceral adipose tissue accumulation after selection for innate cardiovascular fitness.

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