Associations of visceral and abdominal subcutaneous adipose tissue with markers of cardiac and metabolic risk in obese adults

Ian J Neeland, Colby R Ayers, Anand K Rohatgi, Aslan T Turer, Jarett D Berry, Sandeep R Das, Gloria L Vega, Amit Khera, Darren K McGuire, Scott M Grundy, James A de Lemos, Ian J Neeland, Colby R Ayers, Anand K Rohatgi, Aslan T Turer, Jarett D Berry, Sandeep R Das, Gloria L Vega, Amit Khera, Darren K McGuire, Scott M Grundy, James A de Lemos

Abstract

Objective: Visceral (VAT) and abdominal subcutaneous (SAT) adipose tissues contribute to obesity but may have different metabolic and atherosclerosis risk profiles. We sought to determine the associations of abdominal VAT and SAT mass with markers of cardiac and metabolic risk in a large, multiethnic, population-based cohort of obese adults.

Design and methods: Among obese participants in the Dallas Heart Study, we examined the cross-sectional associations of abdominal VAT and SAT mass, assessed by magnetic resonance imaging (MRI) and indexed to body surface area (BSA), with circulating biomarkers of insulin resistance, dyslipidemia, and inflammation (n = 942); and with aortic plaque and liver fat by MRI and coronary calcium by computed tomography (n = 1200). Associations of VAT/BSA and SAT/BSA were examined after adjustment for age, sex, race, menopause, and body mass index.

Results: In multivariable models, VAT significantly associated with the homeostasis model assessment of insulin resistance (HOMA-IR), lower adiponectin, smaller LDL and HDL particle size, larger VLDL size, and increased LDL and VLDL particle number (p < 0.001 for each). VAT also associated with prevalent diabetes, metabolic syndrome, hepatic steatosis, and aortic plaque (p < 0.001 for each). VAT independently associated with C-reactive protein but not with any other inflammatory biomarkers tested. In contrast, SAT associated with leptin and inflammatory biomarkers, but not with dyslipidemia or atherosclerosis. Associations between SAT and HOMA-IR were significant in univariable analyses but attenuated after multivariable adjustment.

Conclusion: VAT associated with an adverse metabolic, dyslipidemic, and atherogenic obesity phenotype. In contrast, SAT demonstrated a more benign phenotype, characterized by modest associations with inflammatory biomarkers and leptin, but no independent association with dyslipidemia, insulin resistance, or atherosclerosis in obese individuals. These findings suggest that abdominal fat distribution defines distinct obesity sub-phenotypes with heterogeneous metabolic and atherosclerosis risk.

Copyright © 2012 The Obesity Society.

Figures

Figure 1. Representative Examples of Abdominal Fat…
Figure 1. Representative Examples of Abdominal Fat and Aortic Plaque by MRI in Two Subjects with Divergent Cardiovascular and Metabolic Phenotypes
Panel A: Transverse abdominal MRI images of VAT and SAT (upper panel) and aortic plaque (lower panel) in a 21 year old black female with BMI of 36 kg/m2 and total body fat of 4.2 kg (41%) demonstrate very low VAT (0.22 kg/m2) and high SAT (4.45 kg/m2), and no aortic plaque (0%). Panel B: In contrast, images of VAT and SAT (upper panel) and aortic plaque (lower panel) in a 59 year old white male with a BMI of 31.4 kg/m2 and total body fat of 4.0 kg (34%) demonstrate very high VAT (1.80 kg/m2) and low SAT (1.46 kg/m2), and high aortic plaque (18%). BMI, body mass index; LDL, low-density lipoprotein; MRI, magnetic resonance imaging; SAT, subcutaneous adipose tissue; VAT, visceral adipose tissue
Figure 2. Adjusted Prevalence of Aortic Plaque…
Figure 2. Adjusted Prevalence of Aortic Plaque by Tertile of VAT/BSA or SAT/BSA in Obese Adults
The adjusted prevalence of aortic plaque increases significantly across sex-specific tertiles of VAT, but decreases across tertiles of SAT, in obese adults. Adjusted for age, sex, race, menopausal status (women only), hypertension, diabetes, smoking, hypercholesterolemia, low HDL cholesterol, glucose-lowering medication, lipid-lowering medication, aspirin, VAT/BSA, and SAT/BSA. p-value for trend across tertiles BSA, body surface area; SAT, subcutaneous adipose tissue; Tert, tertile; VAT, visceral adipose tissue

References

    1. Cornier MA, Despres JP, Davis N, et al. Assessing Adiposity: A Scientific Statement From the American Heart Association. Circulation. 2011;124:1996–2019.
    1. Bays HE, Gonzalez-Campoy JM, Bray GA, et al. Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity. Expert Rev Cardiovasc Ther. 2008;6:343–368.
    1. Tan CY, Vidal-Puig A. Adipose tissue expandability: the metabolic problems of obesity may arise from the inability to become more obese. Biochem Soc Trans. 2008;36:935–940.
    1. Fox CS, Massaro JM, Hoffmann U, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007;116:39–48.
    1. Oka R, Miura K, Sakurai M, et al. Impacts of visceral adipose tissue and subcutaneous adipose tissue on metabolic risk factors in middle-aged Japanese. Obesity (Silver Spring) 2010;18:153–160.
    1. Liu J, Fox CS, Hickson DA, et al. . Impact of abdominal visceral and subcutaneous adipose tissue on cardiometabolic risk factors: the Jackson Heart Study. J Clin Endocrinol Metab. 2010;95:5419–5426.
    1. Pou KM, Massaro JM, Hoffmann U, et al. Visceral and subcutaneous adipose tissue volumes are cross-sectionally related to markers of inflammation and oxidative stress: the Framingham Heart Study. Circulation. 2007;116:1234–1241.
    1. Ducluzeau PH, Manchec-Poilblanc P, Roullier V, et al. Distribution of abdominal adipose tissue as a predictor of hepatic steatosis assessed by MRI. Clin Radiol. 2010;65:695–700.
    1. Wildman RP, Janssen I, Khan UI, et al. Subcutaneous adipose tissue in relation to subclinical atherosclerosis and cardiometabolic risk factors in midlife women. Am J Clin Nutr. 2011;93:719–726.
    1. Bays HE, Fox KM, Grandy S. Anthropometric measurements and diabetes mellitus: clues to the "pathogenic" and "protective" potential of adipose tissue. Metab Syndr Relat Disord. 2010;8:307–315.
    1. Porter SA, Massaro JM, Hoffmann U, Vasan RS, O'Donnel CJ, Fox CS. Abdominal subcutaneous adipose tissue: a protective fat depot? Diabetes Care. 2009;32:1068–1075.
    1. McLaughlin T, Lamendola C, Liu A, Abbasi F. Preferential fat deposition in subcutaneous versus visceral depots is associated with insulin sensitivity. J Clin Endocrinol Metab. 2011;96:E1756–E1760.
    1. Katzmarzyk PT, Bray GA, Greenway FL, et al. Racial differences in abdominal depotspecific adiposity in white and African American adults. Am J Clin Nutr. 2010;91:7–15.
    1. Differences in prevalence of obesity among black, white, and Hispanic adults - United States, 2006–2008. MMWR Morb Mortal Wkly Rep. 2009;58:740–744.
    1. Victor RG, Haley RW, Willett DL, et al. The Dallas Heart Study: a population-based probability sample for the multidisciplinary study of ethnic differences in cardiovascular health. Am J Cardiol. 2004;93:1473–1480.
    1. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143–3421.
    1. Levey AS, Adler S, Caggiula AW, et al. Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease Study. Am J Kidney Dis. 1996;27:652–663.
    1. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–419.
    1. Tikuisis P, Meunier P, Jubenville CE. Human body surface area: measurement and prediction using three dimensional body scans. Eur J Appl Physiol. 2001;85:264–271.
    1. Abate N, Garg A, Coleman R, Grundy SM, Peshock RM. Prediction of total subcutaneous abdominal, intraperitoneal, and retroperitoneal adipose tissue masses in men by a single axial magnetic resonance imaging slice. Am J Clin Nutr. 1997;65:403–408.
    1. Ross R, Leger L, Morris D, de Guise J, Guardo R. Quantification of adipose tissue by MRI: relationship with anthropometric variables. J Appl Physiol. 1992;72:787–795.
    1. Armellini F, Zamboni M, Perdichizzi G, et al. Computed tomography visceral adipose tissue volume measurements of Italians. Predictive equations. Eur J Clin Nutr. 1996;50:290–294.
    1. Szczepaniak LS, Babcock EE, Schick F, et al. Measurement of intracellular triglyceride stores by H spectroscopy: validation in vivo. Am J Physiol. 1999;276:E977–E989.
    1. Vega GL, Adams-Huet B, Peshock R, Willett D, Shah B, Grundy SM. Influence of body fat content and distribution on variation in metabolic risk. J Clin Endocrinol Metab. 2006;91:4459–4466.
    1. Abdullah SM, Khera A, Leonard D, et al. Sex differences in the association between leptin and CRP: results from the Dallas Heart Study. Atherosclerosis. 2007;195:404–410.
    1. Turer AT, Khera A, Ayers CR, et al. Adipose tissue mass and location affect circulating adiponectin levels. Diabetologia. 2011;54:2515–2524.
    1. Khera A, Vega GL, Das SR, et al. Sex differences in the relationship between C-reactive protein and body fat. J Clin Endocrinol Metab. 2009;94:3251–3258.
    1. Jeyarajah EJ, Cromwell WC, Otvos JD. Lipoprotein particle analysis by nuclear magnetic resonance spectroscopy. Clin Lab Med. 2006;26:847–870.
    1. Jain T, Peshock R, McGuire DK, et al. African Americans and Caucasians have a similar prevalence of coronary calcium in the Dallas Heart Study. J Am Coll Cardiol. 2004;44:1011–107.
    1. Rohatgi A, Ayers CR, Khera A, et al. The association between peptidoglycan recognition protein-1 and coronary and peripheral atherosclerosis: Observations from the Dallas Heart Study. Atherosclerosis. 2009;203:569–575.
    1. Long J. Regression Models for Categorical and Limited Dependent Variables. Thousand Oaks, California: Sage; 1997. pp. 187–203.
    1. Goedecke JH, Levitt NS, Lambert EV, et al. Differential effects of abdominal adipose tissue distribution on insulin sensitivity in black and white South African women. Obesity (Silver Spring) 2009;17:1506–1512.
    1. Garg A. Regional adiposity and insulin resistance. J Clin Endocrinol Metab. 2004;89:4206–4210.
    1. Jensen MD. Is visceral fat involved in the pathogenesis of the metabolic syndrome? Human model. Obesity (Silver Spring) 2006;14(Suppl 1):20S–24S.
    1. Goodpaster BH, Krishnaswami S, Harris TB, et al. Obesity, regional body fat distribution, and the metabolic syndrome in older men and women. Arch Intern Med. 2005;165:777–783.
    1. Khashper A, Gaspar T, Azencot M, et al. Visceral abdominal adipose tissue and coronary atherosclerosis in asymptomatic diabetics. Int J Cardiol. 2011 Jun 2; [Epub ahead of print]
    1. Blaha MJ, Rivera JJ, Budoff MJ, et al. Association between obesity, high-sensitivity Creactive protein >/=2 mg/L, and subclinical atherosclerosis: implications of JUPITER from the Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2011;31:1430–1438.
    1. Kronmal RA, McClelland RL, Detrano R, et al. Risk factors for the progression of coronary artery calcification in asymptomatic subjects: results from the Multi-Ethnic Study of Atherosclerosis (MESA) Circulation. 2007;115:2722–2730.
    1. Rexrode KM, Buring JE, Manson JE. Abdominal and total adiposity and risk of coronary heart disease in men. Int J Obes Relat Metab Disord. 2001;25:1047–1056.
    1. Gelber RP, Gaziano JM, Orav EJ, Manson JE, Buring JE, Kurth T. Measures of obesity and cardiovascular risk among men and women. J Am Coll Cardiol. 2008;52:605–615.

Source: PubMed

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