The association of abdominal obesity with cardiovascular risk is often linked to altered secretion of adipose-derived factors and an abnormal lipid profile including formation of atherogenic small dense low density lipoprotein particles (sdLDL). Acylation-stimulating protein (ASP) is an adipose-derived hormone that exhibits potent lipogenic effects. Plasma ASP levels increase in obesity; however, the association of ASP levels with body fat distribution is not yet established, and no study to date has investigated the association of ASP with LDL size. In this study, we examined the association of ASP levels with abdominal obesity measures and the lipid profile including LDL size in 83 men with a wide range of abdominal girths. Regression analysis showed that waist/hip ratio was the main predictor of ASP levels (β = 0.52, ), significantly followed by decreased LDL size. BMI and TG levels, although positively correlated with ASP levels, were excluded as significant predictors in regression analysis. No correlation was found with LDL-C or apoB levels. ASP levels were 62.5% higher in abdominally obese compared to nonobese men. Waist/hip ratio presenting as the main predictor of ASP levels, suggests increased ASP production by abdominal fat which, as proposed previously, may result from resistance to ASP function causing delayed TG clearance and subsequent formation of atherogenic sdLDL. 1. Introduction The link between abdominal (omental) obesity and cardiovascular risk is well recognized. The dyslipidemic profile of abdominal obesity, and its association with atherogenic risk [1, 2] is attributed to insulin resistance and altered secretion of fat derived factors including fatty acids and adipokines such as adiponectin, leptin, interleukin-6, and tumor necrosis factor-alpha [3]. Acylation-stimulating protein (ASP) is another adipokine that was isolated based on its function as a potent fat storage factor. ASP was shown to be comparable to insulin in its fat storing stimulatory effect [4]. Abundant in vivo and in vitro evidence linked ASP function to enhanced triglyceride clearance by promoting fatty acid trapping and fat storage in adipocytes by activating the rate-limiting enzyme for TG synthesis, diacylglycerol acyl transferase [5]. Insulin, on the other hand, activates lipoprotein lipase releasing fatty acids for uptake by adipocytes and inhibits hormone-sensitive lipase which catalyzes fat hydrolysis from adipocytes. ASP acts in a manner that is independent but additive to insulin [6]. ASP levels were shown to increase in obese and hyperlipidemic
References
[1]
J. P. Despres, “Dyslipidaemia and obesity,” Baillière's Clinical Endocrinology and Metabolism, vol. 8, pp. 629–660, 1994.
[2]
B. Tresaco, L. Moreno, J. Ruiz, et al., “Truncal and abdominal fat as determinants of high triglycerides and low HDL-cholesterol in adolescents,” Obesity, vol. 17, no. 5, pp. 1086–1091, 2009.
[3]
R. N. Bergman, S. P. Kim, K. J. Catalano et al., “Why visceral fat is bad: mechanisms of the metabolic syndrome,” Obesity, vol. 14, supplement 1, pp. 16S–19S, 2006.
[4]
K. Cianflone, D. A. K. Roncari, M. Maslowska, A. Baldo, J. Forden, and A. D. Sniderman, “Adipsin/acylation stimulating protein system in human adipocytes: regulation of triacylglycerol synthesis,” Biochemistry, vol. 33, no. 32, pp. 9489–9495, 1994.
[5]
K. Cianflone, Z. Xia, and L. Y. Chen, “Critical review of acylation-stimulating protein physiology in humans and rodents,” Biochimica et Biophysica Acta, vol. 1609, no. 2, pp. 127–143, 2003.
[6]
A. D. Sniderman, M. Maslowska, and K. Cianflone, “Of mice and men (and women) and the acylation-stimulating protein pathway,” Current Opinion in Lipidology, vol. 11, no. 3, pp. 291–296, 2000.
[7]
M. Maslowska, H. Vu, S. Phelis et al., “Plasma acylation stimulating protein, adipsin and lipids in non-obese and obese populations,” European Journal of Clinical Investigation, vol. 29, no. 8, pp. 679–686, 1999.
[8]
K. Cianflone, D. Kalant, E. B. Marliss, R. Gougeon, and A. D. Sniderman, “Response of plasma ASP to a prolonged fast,” International Journal of Obesity, vol. 19, no. 9, pp. 604–609, 1995.
[9]
D. Kalant, R. MacLaren, W. Cui et al., “C5L2 is a functional receptor for acylation-stimulating protein,” The Journal of Biological Chemistry, vol. 280, no. 25, pp. 23936–23944, 2005.
[10]
M. Marcil, H. Vu, W. Cui et al., “Identification of a Novel C5L2 variant (S323I) in a French Canadian family with familial combined hyperlipemia,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 26, no. 7, pp. 1619–1625, 2006.
[11]
J. Saleh, K. Cianflone, T. Chaudhary, H. Al-Riyami, A. R. Al-Abri, and R. Bayoumi, “Increased plasma acylation-stimulating protein correlates with hyperlipidemia at late gestation,” Obesity, vol. 15, no. 3, pp. 646–652, 2007.
[12]
H. A. Koistinen, H. Vidal, S. L. Karonen et al., “Plasma acylation stimulating protein concentration and subcutaneous adipose tissue C3 mRNA expression in nondiabetic and type 2 diabetic men,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 21, no. 6, pp. 1034–1039, 2001.
[13]
Y. Wen, H. Wang, R. MacLaren, J. Wu, H. Lu, and K. Cianflone, “Palmitate and oleate induction of acylation stimulating protein resistance in 3T3-L1 adipocytes and preadipocytes,” Journal of Cellular Biochemistry, vol. 104, no. 2, pp. 391–401, 2008.
[14]
C. Weyer and R. E. Pratley, “Fasting and postprandial plasma concentrations of acylation-stimulation protein (ASP) in lean and obese pima Indians compared to caucasians,” Obesity Research, vol. 7, no. 5, pp. 444–452, 1999.
[15]
M. Ozata, C. Oktenli, M. Gulec et al., “Increased fasting plasma acylation-stimulating protein concentrations in nephrotic syndrome,” Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 2, pp. 853–858, 2002.
[16]
R. Boizel, P. Y. Benhamou, B. Lardy, F. Laporte, T. Foulon, and S. Halimi, “Ratio of triglycerides to HDL cholesterol is an indicator of LDL particle size in patients with type 2 diabetes and normal HDL cholesterol levels,” Diabetes Care, vol. 23, no. 11, pp. 1679–1685, 2000.
[17]
V. Hanak, J. Munoz, J. Teague, A. Stanley, and V. Bittner, “Accuracy of the triglyceride to high-density lipoprotein cholesterol ratio for prediction of the low-density lipoprotein phenotype B,” American Journal of Cardiology, vol. 94, no. 2, pp. 219–222, 2004.
[18]
C. Couillard, N. Bergeron, D. Prud'homme et al., “Postprandial triglyceride response in visceral obesity in men,” Diabetes, vol. 47, no. 6, pp. 953–960, 1998.
[19]
D. Canoy, S. M. Boekholdt, N. Wareham et al., “Body fat distribution and risk of coronary heart disease in men and women in the european prospective investigation into cancer and nutrition in norfolk cohort: a population-based prospective study,” Circulation, vol. 116, no. 25, pp. 2933–2943, 2007.
[20]
J. B. Croft, N. L. Keenan, D. P. Sheridan, F. C. Wheeler, and M. A. Speers, “Waist-to-hip ratio in a biracial population: measurement, implications, and cautions for using guidelines to define high risk for cardiovascular disease,” Journal of the American Dietetic Association, vol. 95, no. 1, pp. 60–64, 1995.
[21]
S. Lemieux, D. Prud'homme, C. Bouchard, A. Tremblay, and J. P. Després, “A single threshold value of waist girth identifies normal-weight and overweight subjects with excess visceral adipose tissue,” The American Journal of Clinical Nutrition, vol. 64, no. 5, pp. 685–693, 1996.
[22]
J. Saleh, L. K. M. Summers, K. Cianflone, B. A. Fielding, A. D. Sniderman, and K. N. Frayn, “Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period,” Journal of Lipid Research, vol. 39, no. 4, pp. 884–891, 1998.
[23]
A. V. Nichols, R. M. Krauss, and T. A. Musliner, “Nondenaturing polyacrylamide gradient gel electrophoresis,” Methods in Enzymology, vol. 128, pp. 417–431, 1986.
[24]
C. Maruyama, K. Imamura, and T. Teramoto, “Assessment of LDL particle size by triglyceride/HDL-cholesterol ratio in non-diabetic, healthy subjects without prominent hyperlipidemia,” Journal of Atherosclerosis and Thrombosis, vol. 10, no. 3, pp. 186–191, 2003.
[25]
M. C. Carr and J. D. Brunzell, “Abdominal obesity and dyslipidemia in the metabolic syndrome: importance of type 2 diabetes and familial combined hyperlipidemia in coronary artery disease risk,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 6, pp. 2601–2607, 2004.
[26]
R. A. Wetsel, J. Kildsgaard, E. Zsigmond, W. Liao, and L. Chan, “Genetic deficiency of acylation stimulating protein (ASP(C3ades-Arg)) does not cause hyperapobetalipoproteinemia in mice,” The Journal of Biological Chemistry, vol. 274, no. 27, pp. 19429–19433, 1999.
[27]
K. Cianflone, R. Zakarian, C. Couillard, B. Delplanque, J.-P. Despres, and A. D. Sniderman, “Fasting acylation-stimulating protein is predictive of postprandial triglyceride clearance,” Journal of Lipid Research, vol. 45, no. 1, pp. 124–131, 2004.
[28]
L. J. Martin, K. Cianflone, R. Zakarian et al., “Bivariate linkage between acylation-stimulating protein and BMI and high-density lipoproteins,” Obesity Research, vol. 12, no. 4, pp. 669–678, 2004.
[29]
J. Saleh, N. Christou, and K. Cianflone, “Regional specificity of ASP binding in human adipose tissue,” American Journal of Physiology, vol. 276, no. 5, part 1, pp. E815–E821, 1999.
[30]
M. H. Maslowska, A. D. Sniderman, L. D. MacLean, and K. Cianflone, “Regional differences in triacylglycerol synthesis in adipose tissue and in cultured preadipocytes,” Journal of Lipid Research, vol. 34, no. 2, pp. 219–228, 1993.
[31]
J. Saleh, N. Al-Wardy, H. Farhan, M. Al-Khanbashi, and K. Cianflone, “Acylation stimulating protein: a female lipogenic factor?” Obesity Reviews, vol. 12, no. 6, pp. 440–448, 2011.
[32]
R. E. Morton, “Cholesteryl ester transfer protein and its plasma regulator: lipid transfer inhibitor protein,” Current Opinion in Lipidology, vol. 10, no. 4, pp. 321–327, 1999.
[33]
L. Lagrost, H. Gandjini, A. Athias, V. Guyard-Dangremont, C. Lallemant, and P. Gambert, “Influence of plasma cholesteryl ester transfer activity on the LDL and HDL distribution profiles in normolipidemic subjects,” Arteriosclerosis and Thrombosis, vol. 13, no. 6, pp. 815–825, 1993.
[34]
M. Ozata, D. Gungor, M. Turan et al., “Improved glycemic control increases fasting plasma acylation-stimulating protein and decreases leptin concentrations in type II diabetic subjects,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 8, pp. 3659–3664, 2001.
[35]
D. C. W. Lau, B. Dhillon, H. Yan, P. E. Szmitko, and S. Verma, “Adipokines: molecular links between obesity and atheroslcerosis,” American Journal of Physiology, vol. 288, no. 5, pp. H2031–H2041, 2005.
