Background. High adiponectin/leptin ratio may be protective from metabolic risks imparted by high triglyceride, low HDL, and insulin resistance. Methods. This cross-sectional study examines plasma adipokine levels in 428 adult men who were subgrouped according to low (<6.5？μg/mL)and high (≥6.5？μg/mL)adiponectin levels or a low or high ratio of adiponectin/leptin. Results. Men with high adiponectin/leptin ratio had lower plasma triglyceride and higher HDL cholesterol than those with low ratio. Similarly, those with high adiponectin/leptin ratio had lower TG/HDL cholesterol ratio and HOMA2-IR than those with low ratio. In contrast, levels of adiponectin or the ratio of adiponectin/leptin did not associate with systolic blood pressure. But the ratio of adiponectin/leptin decreased progressively with the increase in the number of risk factors for metabolic syndrome. Conclusion. Adipokine levels may reflect adipose tissue triglyceride storage capacity and insulin sensitivity. Leptin is an index of fat mass, and adiponectin is a biomarker of triglyceride metabolism and insulin sensitivity. Men with high adiponectin/leptin ratios have better triglyceride profile and insulin sensitivity than men with a low ratio regardless of waist girth. 1. Introduction Excess abdominal body fat is implicated in the etiology of the metabolic syndrome, a cluster of risk factors for cardiovascular disease and for type 2 diabetes mellitus. The risk factors include dyslipidemia (high triglyceride and/or low HDL cholesterol), insulin resistance, and hypertension [1]. Abdominal obesity is assessed by waist girth, and several cut points of high-risk waist girth have been recommended to identify at-risk individuals based on gender and ethnicity [2]. Reaching a consensus on a sex-specific, global definition of high-risk waist girth has proved to be challenging [3]. However, a global cut point may be impractical because individuals vary in susceptibility to obesity-induced risk for metabolic syndrome. An alternative to using waist girth is to identify biomarkers that are causally related to the metabolic risks and that reflect a function of adipose tissue. Two adipokines, leptin and adiponectin, may be risk markers of fat-induced dyslipidemia and insulin resistance. Both adipokines are reportedly associated with risk for type 2 diabetes and with cardiovascular disease. Plasma levels of leptin correlate positively with total body fat [4–6] and with adipocyte number in men [7]. In addition, individuals at high risk seemingly have high levels of plasma leptin [8]. The levels are directly
References
[1]
National Cholesterol Education Program (NCEP) Expert Panel on Detection, “Evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). 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, vol. 106, pp. 3143–3421, 2002.
[2]
Alberti, R. H. Eckel, S. M. Grundy et al., “Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; National heart, lung, and blood institute; American heart association; World heart federation; International atherosclerosis society; And international association for the study of obesity,” Circulation, vol. 120, no. 16, pp. 1640–1645, 2009.
[3]
A. J. Cameron, R. A. Sicree, P. Z. Zimmet et al., “Cut-points for waist circumference in Europids and South Asians,” Obesity, vol. 18, no. 10, pp. 2039–2046, 2010.
[4]
R. V. Considine, M. K. Sinha, M. L. Heiman et al., “Serum immunoreactive-leptin concentrations in normal-weight and obese humans,” The New England Journal of Medicine, vol. 334, no. 5, pp. 292–295, 1996.
[5]
C. E. Ruhl, J. E. Everhart, J. Ding et al., “Serum leptin concentrations and body adipose measures in older black and white adults,” American Journal of Clinical Nutrition, vol. 80, no. 3, pp. 576–583, 2004.
[6]
Mapfei, Halaas, Ravussin et al., “Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects,” Nature Medicine, vol. 1, no. 11, pp. 1155–1161, 1995.
[7]
C. Couillard, P. Mauriège, P. Imbeault, D. Prud'homme, A. Nadeau, and A. Tremblay, “Hyperleptinemia is more closely associated with adipose cell hypertrophy than with adipose tissue hyperplasia,” International Journal of Obesity, vol. 24, no. 6, pp. 782–788, 2000.
[8]
Lilja, Rolandsson, Shaw et al., “Higher leptin levels in Asian Indians than Creoles and Europids: a potential explanation for increased metabolic risk,” International Journal of Obesity, vol. 34, no. 5, pp. 878–885, 2010.
[9]
Klein, Coppack, Mohamed-Ali, and Landt, “Adipose tissue leptin production and plasma leptin kinetics in humans,” Diabetes, vol. 45, no. 3, pp. 984–987, 1996.
[10]
V. Van Harmelen, S. Reynisdottir, P. Eriksson et al., “Leptin secretion from subcutaneous and visceral adipose tissue in women,” Diabetes, vol. 47, no. 6, pp. 913–917, 1998.
[11]
H. Kondo, L. Shimomura, Y. Matsukawa et al., “Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome,” Diabetes, vol. 51, no. 7, pp. 2325–2328, 2002.
[12]
Y. Matsuzawa, T. Funahashi, S. Kihara, and I. Shimomura, “Adiponectin and metabolic syndrome,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 24, no. 1, pp. 29–33, 2004.
[13]
A. T. Turer, A. Khera, C. R. Ayers, et al., “Adipose tissue mass and location affect circulating adiponectin levels,” Diabetologia, vol. 54, no. 10, pp. 2515–2524, 2011.
[14]
J. J. Clarenbach, S. M. Grundy, N. Palacio, and G. L. Vega, “Relationship of apolipoprotein B levels to the number of risk factors for metabolic syndrome,” Journal of Investigative Medicine, vol. 55, no. 5, pp. 237–247, 2007.
[15]
G. L. Vega, M. Chandalia, L. S. Szczepaniak, and S. M. Grundy, “Metabolic correlates of nonalcoholic fatty liver in women and men,” Hepatology, vol. 46, no. 3, pp. 716–722, 2007.
[16]
J. C. Levy, D. R. Matthews, and M. P. Hermans, “Correct homeostasis model assessment (HOMA) evaluation uses the computer program,” Diabetes Care, vol. 21, no. 12, pp. 2191–2192, 1998.
[17]
S. Zhu, S. B. Heymsfield, H. Toyoshima, Z. Wang, A. Pietrobelli, and S. Heshka, “Race-ethnicity-specific waist circumference cutoffs for identifying cardiovascular disease risk factors,” American Journal of Clinical Nutrition, vol. 81, no. 2, pp. 409–415, 2005.
[18]
J. Y. Park, A. Y. Chong, E. K. Cochran et al., “Type 1 diabetes associated with acquired generalized lipodystrophy and insulin resistance: the effect of long-term leptin therapy,” Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 1, pp. 26–31, 2008.
[19]
E. A. Oral, V. Simha, E. Ruiz et al., “Leptin-replacement therapy for lipodystrophy,” The New England Journal of Medicine, vol. 346, no. 8, pp. 570–578, 2002.
[20]
P. M. Zelissen, K. Stenlof, M. E. Lean, et al., “Effect of three treatment schedules of recombinant methionyl human leptin on body weight in obese adults: a randomized, placebo-controlled trial,” Diabetes, Obesity and Metabolism, vol. 7, no. 6, pp. 755–761, 2005.
[21]
C. S. Mantzoros, F. Magkos, M. Brinkoetter, et al., “Leptin in human physiology and pathophysiology,” American Journal of Physiology, vol. 301, no. 4, pp. E567–E584, 2011.
[22]
A. Strobel, T. Issad, L. Camoin, M. Ozata, and D. Strosberg, “A leptin missense mutation associated with hypogonadism and morbid obesity,” Nature Genetics, vol. 18, no. 3, pp. 213–215, 1998.
[23]
K. Clément, C. Vaisse, N. Lahlou et al., “A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction,” Nature, vol. 392, no. 6674, pp. 398–401, 1998.
[24]
I. S. Farooqi, S. A. Jebb, G. Langmack et al., “Effects of recombinant leptin therapy in a child with congenital leptin deficiency,” The New England Journal of Medicine, vol. 341, no. 12, pp. 879–884, 1999.
[25]
A. S. Ryan, D. M. Berman, B. J. Nicklas et al., “Plasma adiponectin and leptin levels, body composition, and glucose utilization in adult women with wide ranges of age and obesity,” Diabetes Care, vol. 26, no. 8, pp. 2383–2388, 2003.
[26]
L. Qiao, C. Zou, D. R. van der Westhuyzen, and J. Shao, “Adiponectin reduces plasma triglyceride by increasing VLDL triglyceride catabolism,” Diabetes, vol. 57, no. 7, pp. 1824–1833, 2008.
[27]
T. P. Combs, U. B. Pajvani, A. H. Berg, et al., “A transgenic mouse with a deletion in the collagenous domain of adiponectin displays elevated circulating adiponectin and improved insulin sensitivity,” Endocrinology, vol. 145, pp. 367–383, 2004.
[28]
T. Yamauchi, J. Kamon, H. Waki, et al., “Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis,” The Journal of Biological Chemistry, vol. 278, no. 4, pp. 2461–2468, 2003.
[29]
I. B. Bauche, S. A. El Mkadem, A. Pottier et al., “Overexpression of adiponectin targeted to adipose tissue in transgenic mice: impaired adipocyte differentiation,” Endocrinology, vol. 148, no. 4, pp. 1539–1549, 2007.
[30]
R. Baratta, S. Amato, C. Degano et al., “Adiponectin relationship with lipid metabolism is independent of body fat mass: evidence from both cross-sectional and intervention studies,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 6, pp. 2665–2671, 2004.
[31]
B. Vergès, J. M. Petit, L. Duvillard et al., “Adiponectin is an important determinant of ApoA-I catabolism,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 26, no. 6, pp. 1364–1369, 2006.
[32]
D. C. Chan, P. H. R. Barrett, E. M. M. Ooi, J. Ji, D. T. Chan, and G. F. Watts, “Very low density lipoprotein metabolism and plasma adiponectin as predictors of high-density lipoprotein apolipoprotein a-l kinetics in obese and nonobese men,” Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 3, pp. 989–997, 2009.
[33]
J. G. Schneider, M. Von Eynatten, S. Schiekofer, P. P. Nawroth, and K. A. Dugi, “Low plasma adiponectin levels are associated with increased hepatic lipase activity in vivo,” Diabetes Care, vol. 28, no. 9, pp. 2181–2186, 2005.
[34]
J. J. Clarenbach, G. L. Vega, B. Adams-Huet, R. V. Considine, M. Ricks, and A. E. Sumner, “Variability in postheparin hepatic lipase activity is associated with plasma adiponectin levels in African Americans,” Journal of Investigative Medicine, vol. 55, no. 4, pp. 187–194, 2007.
[35]
F. M. Finucane, J. Luan, N. J. Wareham, et al., “Correlation of the leptin: adiponectin ratio with measures of insulin resistance in non-diabetic individuals,” Diabetologia, vol. 52, no. 11, pp. 2345–2349, 2009.
[36]
N. Oda, S. Imamura, T. Fujita et al., “The ratio of leptin to adiponectin can be used as an index of insulin resistance,” Metabolism, vol. 57, no. 2, pp. 268–273, 2008.
[37]
R. P. Wildman, P. Muntner, K. Reynolds et al., “The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999–2004),” Archives of Internal Medicine, vol. 168, no. 15, pp. 1617–1624, 2008.
[38]
M. Blüher, “The distinction of metabolically “healthy” from “unhealthy” obese individuals,” Current Opinion in Lipidology, vol. 21, pp. 38–43, 2010.
[39]
M. Brochu, A. Tchernof, I. J. Dionne, et al., “What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women?” The Journal of Clinical Endocrinology & Metabolism, vol. 86, pp. 1020–1025, 2001.
[40]
N. Stefan, K. Kantartzis, J. Machann et al., “Identification and characterization of metabolically benign obesity in humans,” Archives of Internal Medicine, vol. 168, no. 15, pp. 1609–1616, 2008.
