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Published in: Cardiovascular Diabetology 1/2015

Open Access 01-12-2015 | Original investigation

Role of adiponectin and free fatty acids on the association between abdominal visceral fat and insulin resistance

Authors: Aida Medina-Urrutia, Carlos Posadas-Romero, Rosalinda Posadas-Sánchez, Esteban Jorge-Galarza, Teresa Villarreal-Molina, María del Carmen González-Salazar, Guillermo Cardoso-Saldaña, Gilberto Vargas-Alarcón, Margarita Torres-Tamayo, Juan Gabriel Juárez-Rojas

Published in: Cardiovascular Diabetology | Issue 1/2015

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Abstract

Background

Experimental studies have shown that high free fatty acid (FFA) and low adiponectin (ADIPO) levels are involved in the mechanisms by which adiposity promotes insulin resistance (IR). However, no previous clinical studies have simultaneously analysed the relative contribution of FFA and ADIPO levels on the relation of abdominal visceral fat (AVF) with insulin resistance.

Objective

To analyse the contribution of low ADIPO (adiponectin < =p25th: 8.67 μg/mL in women and 5.30 μg/mL in men), and high FFAs (FFAs > =p75th: 0.745 mEq/L in women and 0.60 mEq/L in men) to the association of high AVF (AVF > =p75th: 127 cm2 in women; 152.7 cm2 in men) with insulin resistance (HOMA-IR > =75th: 3.58 in women and 3.12 in men), in non-diabetic subjects.

Material and methods

A cross-sectional analysis was performed including 1217 control participants of the Genetics of Atherosclerotic Disease study (GEA). Clinical, tomographic and biochemical parameters were measured in all participants. Logistic regression models were used to assess the association of high AVF with IR stratifying according to gender, and to normal or low ADIPO and normal or high FFA serum levels.

Results

In comparison to referent group, in men low ADIPO unlike high FFA increased the risk of IR. Females with normal AVF and low ADIPO, or high AVF and normal ADIPO had aprox 3 folds risk of IR (OR [IC95%]: 3.7 [2.1-6.6], p < 0.001, and 3.4 [2.0-5.7], p < 0.001; respectively). The risk increased to 7.6 [4.2-13.8], p < 0.001 when high AVF and low ADIPO were present. Irrespective of AVF, the effect of low ADIPO on IR was higher than that seen for high FFA. Besides, our results suggest an additive effect of high AVF, high FFA and low ADIPO on the IR prevalence.

Conclusions

The present study provides novel and important information about the combined effect of high AVF and low ADIPO on the risk of IR. Furthermore, our data suggest that the effect of low adiponectin levels on the high AVF-IR association is stronger than that observed for high FFA, suggesting that adiponectin could be used as biomarker to identify subjects at high risk for T2DM and CAD.
Literature
2.
go back to reference Meigs JB, Wilson PW, Fox CS, Vasan RS, Nathan DM, Sullivan LM, et al. Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease. J Clin Endocrinol Metab. 2006;91:2906–12.CrossRefPubMed Meigs JB, Wilson PW, Fox CS, Vasan RS, Nathan DM, Sullivan LM, et al. Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease. J Clin Endocrinol Metab. 2006;91:2906–12.CrossRefPubMed
3.
go back to reference Ortega FB, Lee DC, Katzmarzyk PT, Ruiz JR, Sui X, Church TS, et al. The intriguing metabolically healthy but obese phenotype: cardiovascular prognosis and role of fitness. Eur Heart J. 2013;34:389–97.CrossRefPubMedCentralPubMed Ortega FB, Lee DC, Katzmarzyk PT, Ruiz JR, Sui X, Church TS, et al. The intriguing metabolically healthy but obese phenotype: cardiovascular prognosis and role of fitness. Eur Heart J. 2013;34:389–97.CrossRefPubMedCentralPubMed
4.
go back to reference Stefan N, Häring HU, Hu FB, Schulze MB. Metabolically healthy obesity: epidemiology, mechanisms, and clinical implications. Lancet Diabetes Endocrinol. 2013;1:152–62.CrossRefPubMed Stefan N, Häring HU, Hu FB, Schulze MB. Metabolically healthy obesity: epidemiology, mechanisms, and clinical implications. Lancet Diabetes Endocrinol. 2013;1:152–62.CrossRefPubMed
5.
go back to reference Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007;116:39–48.CrossRefPubMed Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007;116:39–48.CrossRefPubMed
6.
go back to reference Carr DB, Utzschneider KM, Hull RL, Kodama K, Retzlaff BM, Brunzell JD, et al. Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome. Diabetes. 2004;53:2087–94.CrossRefPubMed Carr DB, Utzschneider KM, Hull RL, Kodama K, Retzlaff BM, Brunzell JD, et al. Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome. Diabetes. 2004;53:2087–94.CrossRefPubMed
7.
go back to reference Messier V, Karelis AD, Prud’homme D, Primeau V, Brochu M, Rabasa-Lhoret R. Identifying metabolically healthy but obese individuals in sedentary postmenopausal women. Obesity. 2010;18:911–7.CrossRefPubMed Messier V, Karelis AD, Prud’homme D, Primeau V, Brochu M, Rabasa-Lhoret R. Identifying metabolically healthy but obese individuals in sedentary postmenopausal women. Obesity. 2010;18:911–7.CrossRefPubMed
8.
go back to reference Perseghin G, Petersen K, Shulman GI. Cellular mechanism of insulin resistance: potential links with inflammation. Int J Obes Relat Metab Disord. 2003;27:S6–11.CrossRefPubMed Perseghin G, Petersen K, Shulman GI. Cellular mechanism of insulin resistance: potential links with inflammation. Int J Obes Relat Metab Disord. 2003;27:S6–11.CrossRefPubMed
9.
go back to reference Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 2012;425:560–4.CrossRefPubMed Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 2012;425:560–4.CrossRefPubMed
10.
11.
go back to reference Capurso C, Capurso A. From excess adiposity to insulin resistance: the role of free fatty acids. Vascul Pharmacol. 2012;57:91–7.CrossRefPubMed Capurso C, Capurso A. From excess adiposity to insulin resistance: the role of free fatty acids. Vascul Pharmacol. 2012;57:91–7.CrossRefPubMed
12.
go back to reference Miller MR, Pereira RI, Langefeld CD, Lorenzo C, Rotter JI, Chen YD, et al. Levels of free fatty acids (FFA) are associated with insulin resistance but do not explain the relationship between adiposity and insulin resistance in Hispanic Americans: the IRAS Family Study. J Clin Endocrinol Metab. 2012;97:3285–91.CrossRefPubMedCentralPubMed Miller MR, Pereira RI, Langefeld CD, Lorenzo C, Rotter JI, Chen YD, et al. Levels of free fatty acids (FFA) are associated with insulin resistance but do not explain the relationship between adiposity and insulin resistance in Hispanic Americans: the IRAS Family Study. J Clin Endocrinol Metab. 2012;97:3285–91.CrossRefPubMedCentralPubMed
13.
go back to reference Villarreal-Molina T, Posadas-Romero C, Romero-Hidalgo S, Antúnez-Argüelles E, Bautista-Grande A, Vargas-Alarcón G, et al. The ABCA1 gene R230C variant is associated with decreased risk of premature coronary artery disease: the genetics of atherosclerotic disease (GEA) study. PLoS One. 2012;7:e49285.CrossRefPubMedCentralPubMed Villarreal-Molina T, Posadas-Romero C, Romero-Hidalgo S, Antúnez-Argüelles E, Bautista-Grande A, Vargas-Alarcón G, et al. The ABCA1 gene R230C variant is associated with decreased risk of premature coronary artery disease: the genetics of atherosclerotic disease (GEA) study. PLoS One. 2012;7:e49285.CrossRefPubMedCentralPubMed
14.
go back to reference DeLong DM, DeLong ER, Wood PD, Lippel K, Rifkind BM. A comparison of methods for the estimation of plasma low- and very low-density lipoprotein cholesterol.The Lipid Research Clinics Prevalence Study. JAMA. 1986;256:2372–7.CrossRefPubMed DeLong DM, DeLong ER, Wood PD, Lippel K, Rifkind BM. A comparison of methods for the estimation of plasma low- and very low-density lipoprotein cholesterol.The Lipid Research Clinics Prevalence Study. JAMA. 1986;256:2372–7.CrossRefPubMed
15.
go back to reference 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 concentration in man. Diabetologia. 1985;28:412–9.CrossRefPubMed 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 concentration in man. Diabetologia. 1985;28:412–9.CrossRefPubMed
17.
go back to reference Kvist H, Chowdhury B, Grangard U, Tylén U, Sjöström L. Total and visceral adipose-tissue volumes derived from measurement with computed tomography in adult men and women: predicted equations. Am J Clin Nutr. 1988;48:1351–61.PubMed Kvist H, Chowdhury B, Grangard U, Tylén U, Sjöström L. Total and visceral adipose-tissue volumes derived from measurement with computed tomography in adult men and women: predicted equations. Am J Clin Nutr. 1988;48:1351–61.PubMed
18.
go back to reference Oka R, Kobayashi J, Inazu A, Yagi K, Miyamoto S, Sakurai M, et al. Contribution of visceral adiposity and insulin resistance to metabolic risk factors in Japanese men. Metabolism. 2010;59:748–54.CrossRefPubMed Oka R, Kobayashi J, Inazu A, Yagi K, Miyamoto S, Sakurai M, et al. Contribution of visceral adiposity and insulin resistance to metabolic risk factors in Japanese men. Metabolism. 2010;59:748–54.CrossRefPubMed
19.
go back to reference Kishida K, Kim KK, Funahashi T, Matsuzawa Y, Kang HC, Shimomura I. Relationships between circulating adiponectin levels and fat distribution in obese subjects. J AtherosclerThromb. 2011;18:592–5. Kishida K, Kim KK, Funahashi T, Matsuzawa Y, Kang HC, Shimomura I. Relationships between circulating adiponectin levels and fat distribution in obese subjects. J AtherosclerThromb. 2011;18:592–5.
20.
go back to reference Matsushita Y, Nakagawa T, Yamamoto S, Kato T, Ouchi T, Kikuchi N, et al. Adiponectin and visceral fat associate with cardiovascular risk factors. Obesity. 2014;22:287–91.CrossRefPubMed Matsushita Y, Nakagawa T, Yamamoto S, Kato T, Ouchi T, Kikuchi N, et al. Adiponectin and visceral fat associate with cardiovascular risk factors. Obesity. 2014;22:287–91.CrossRefPubMed
21.
go back to reference Fisman EZ, Tenenbaum A. Adiponectin: a manifold therapeutic target formetabolic syndrome, diabetes, and coronary disease? Cardiovasc Diabetol. 2014;13:103.CrossRefPubMedCentralPubMed Fisman EZ, Tenenbaum A. Adiponectin: a manifold therapeutic target formetabolic syndrome, diabetes, and coronary disease? Cardiovasc Diabetol. 2014;13:103.CrossRefPubMedCentralPubMed
22.
go back to reference Aguilar-Salinas CA, García EG, Robles L, Riaño D, Ruiz-Gomez DG, García-Ulloa AC, et al. High adiponectin concentrations are associated with the metabolically healthy obese phenotype. J Clin Endocrinol Metab. 2008;93:4075–9.CrossRefPubMed Aguilar-Salinas CA, García EG, Robles L, Riaño D, Ruiz-Gomez DG, García-Ulloa AC, et al. High adiponectin concentrations are associated with the metabolically healthy obese phenotype. J Clin Endocrinol Metab. 2008;93:4075–9.CrossRefPubMed
23.
go back to reference Nakamura MT. YudellBE Loor JJ. Regulation of energy metabolism by long-chain fatty acids. Prog Lipid Res. 2014;53:124–44.CrossRefPubMed Nakamura MT. YudellBE Loor JJ. Regulation of energy metabolism by long-chain fatty acids. Prog Lipid Res. 2014;53:124–44.CrossRefPubMed
24.
go back to reference Björntorp P. “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis. 1990;10:493–6.CrossRefPubMed Björntorp P. “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis. 1990;10:493–6.CrossRefPubMed
25.
go back to reference He H, Ni Y, Chen J, Zhao Z, Zhong J, Liu D, et al. Sex difference in cardiometabolic risk profile and adiponectin expression in subjects with visceral fat obesity. Transl Res. 2010;155:71–7.CrossRefPubMed He H, Ni Y, Chen J, Zhao Z, Zhong J, Liu D, et al. Sex difference in cardiometabolic risk profile and adiponectin expression in subjects with visceral fat obesity. Transl Res. 2010;155:71–7.CrossRefPubMed
26.
go back to reference Gao Z, Zhang X, Zuberi A, Hwang D, Quon MJ, Lefevre M, et al. Inhibition of insulin sensitivity by free fatty acids requires activation of multiple serine kinases in 3 T3-L1 adipocytes. Mol Endocrinol. 2004;18:2024–34.CrossRefPubMed Gao Z, Zhang X, Zuberi A, Hwang D, Quon MJ, Lefevre M, et al. Inhibition of insulin sensitivity by free fatty acids requires activation of multiple serine kinases in 3 T3-L1 adipocytes. Mol Endocrinol. 2004;18:2024–34.CrossRefPubMed
27.
go back to reference Armoni M, Harel C, Bar-Yoseph F, Milo S, Karnieli E. Free fatty acids repress the GLUT4 gene expression in cardiac muscle via novel response elements. J Biol Chem. 2005;280:34786–95.CrossRefPubMed Armoni M, Harel C, Bar-Yoseph F, Milo S, Karnieli E. Free fatty acids repress the GLUT4 gene expression in cardiac muscle via novel response elements. J Biol Chem. 2005;280:34786–95.CrossRefPubMed
28.
go back to reference Holland WL, Miller RA, Wang ZV, Sun K, Barth BM, Bui HH, et al. Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nat Med. 2011;17:55–63.CrossRefPubMedCentralPubMed Holland WL, Miller RA, Wang ZV, Sun K, Barth BM, Bui HH, et al. Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nat Med. 2011;17:55–63.CrossRefPubMedCentralPubMed
29.
go back to reference Plaisance EP, Grandjean PW, Judd RL, Jones KW, Taylor JK. The influence of sex, body composition, and nonesterified fatty acids on serum adipokine concentrations. Metabolism. 2009;58:1557–63.CrossRefPubMed Plaisance EP, Grandjean PW, Judd RL, Jones KW, Taylor JK. The influence of sex, body composition, and nonesterified fatty acids on serum adipokine concentrations. Metabolism. 2009;58:1557–63.CrossRefPubMed
30.
go back to reference Kishida K, Funahashi T, Shimomura I. Adiponectin as a routine clinical biomarker. Best Pract Res Clin Endocrinol Metab. 2014;28:119–30.CrossRefPubMed Kishida K, Funahashi T, Shimomura I. Adiponectin as a routine clinical biomarker. Best Pract Res Clin Endocrinol Metab. 2014;28:119–30.CrossRefPubMed
31.
go back to reference Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care. 2000;23:57–63.CrossRefPubMed Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care. 2000;23:57–63.CrossRefPubMed
32.
go back to reference Bonora E, Kiechl S, Willeit J, Oberhollenzer F, Egger G, Targher G, et al. Prevalence of insulin resistance in metabolic disorders: the Bruneck Study. Diabetes. 1998;47:1643–9.CrossRefPubMed Bonora E, Kiechl S, Willeit J, Oberhollenzer F, Egger G, Targher G, et al. Prevalence of insulin resistance in metabolic disorders: the Bruneck Study. Diabetes. 1998;47:1643–9.CrossRefPubMed
33.
go back to reference Balkau B, Charles MA. Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med. 1999;16:442–3.CrossRefPubMed Balkau B, Charles MA. Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med. 1999;16:442–3.CrossRefPubMed
34.
go back to reference Sulistyoningrum DC, Gasevic D, Lear SA, Ho J, Mente A, Devlin AM. Total and high molecular weight adiponectin and ethnic-specific differences in adiposity and insulin resistance: a cross-sectional study. Cardiovasc Diabetol. 2013;12:170.CrossRefPubMedCentralPubMed Sulistyoningrum DC, Gasevic D, Lear SA, Ho J, Mente A, Devlin AM. Total and high molecular weight adiponectin and ethnic-specific differences in adiposity and insulin resistance: a cross-sectional study. Cardiovasc Diabetol. 2013;12:170.CrossRefPubMedCentralPubMed
35.
go back to reference Hanley AJ, Bowden D, Wagenknecht LE, Balasubramanyam A, Langfeld C, Saad MF, et al. Associations of adiponectin with body fat distribution and insulin sensitivity in nondiabetic Hispanics and African-Americans. J Clin Endocrinol Metab. 2007;92:2665–71.CrossRefPubMed Hanley AJ, Bowden D, Wagenknecht LE, Balasubramanyam A, Langfeld C, Saad MF, et al. Associations of adiponectin with body fat distribution and insulin sensitivity in nondiabetic Hispanics and African-Americans. J Clin Endocrinol Metab. 2007;92:2665–71.CrossRefPubMed
Metadata
Title
Role of adiponectin and free fatty acids on the association between abdominal visceral fat and insulin resistance
Authors
Aida Medina-Urrutia
Carlos Posadas-Romero
Rosalinda Posadas-Sánchez
Esteban Jorge-Galarza
Teresa Villarreal-Molina
María del Carmen González-Salazar
Guillermo Cardoso-Saldaña
Gilberto Vargas-Alarcón
Margarita Torres-Tamayo
Juan Gabriel Juárez-Rojas
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2015
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-015-0184-5

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