| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Family Medicine (K.-C.H.), Division of Endocrinology and Metabolism (L.-M.C., T.-Y.T., W.-S.Y.), Department of Internal Medicine, National Taiwan University Hospital; and Institute of Epidemiology (C.-L.C.), College of Public Health, and Graduate Institute of Clinical Medicine (L.-M.C., S.-R.H., W.-S.Y.), College of Medicine, National Taiwan University, Taipei 100, Taiwan
Address all correspondence and requests for reprints to: Wei-Shiung Yang, M.D., Ph.D., No. 1 Chang-Teh ST, Taipei 100, Taiwan. E-mail: wsyang{at}ha.mc.ntu.edu.tw.
| Abstract |
|---|
|
|
|---|
= -0.47, P = 0.000) and diastolic blood pressure (
= -0.30, P = 0.014). In linear regression models with adjustment for age and the other anthropometric or metabolic factors, only the SBP, but not the diastolic blood pressure, was independently related to the plasma adiponectin levels. The mean plasma adiponectin levels between the subjects in the lowest quartile of SBP (SBP
100 mm Hg) and those in the highest quartile (SBP
118 mm Hg) were significantly different (P = 0.035). In conclusion, the SBP is inversely related to the plasma adiponectin independent of the other variables of the MS and other risk factors of CAD in healthy adolescent females. This further strengthens the potential roles of adiponectin in the pathophysiology of MS and CAD. | Introduction |
|---|
|
|
|---|
In human studies, the plasma levels of adiponectin were consistently reported to correlate negatively with body mass index (BMI), waist circumference, plasma glucose, insulin, and triglycerides (TGs) but positively with high-density lipoprotein cholesterol (HDL-C) (14, 15, 16, 17, 18, 19, 20, 21). Hypoadiponectinemia was documented in subjects with obesity, type 2 diabetes mellitus, dyslipidemia, and CAD (9, 20, 21). We previously also reported that the subjects with more CAD risk factors had lower plasma adiponectin levels (15).
In contrast to the consistent demonstration of the relationship between plasma adiponectin and the above-mentioned metabolic variables, how plasma adiponectin is related to blood pressures, the other major component of MS and a major CAD risk factor, is still controversial. Three reports suggested a negative relationship between plasma adiponectin levels and blood pressures (16, 22, 23). Our previous study of 180 overweight/obese Asian subjects showed no correlation between blood pressure and plasma adiponectin levels (15). More surprisingly, one report showed higher plasma adiponectin levels in 36 uncomplicated hypertensive subjects than those of normotensives, especially among males (24). The causes underlying the contradictory results from these five studies are not clear at present. We speculated that among the adult subjects having many metabolic abnormalities, the relation between plasma adiponectin and blood pressures may be difficult to be demonstrated (15). Here we report the relationship between blood pressures and plasma adiponectin levels among a group of nondiabetic adolescent females, who were younger and had healthier metabolic profiles than the subjects in the previous five studies (15, 16, 22, 23, 24). Therefore, the relationship between plasma adiponectin and blood pressures may be less likely masked by the other variables. In this report, we found that the plasma adiponectin levels were related in an inverse manner to both the systolic blood pressure (SBP) and diastolic blood pressure (DBP). The SBP especially appeared to be related to the plasma adiponectin levels independent of the other variables related to MS or CAD.
| Subjects and Methods |
|---|
|
|
|---|
Sixty-eight nondiabetic adolescent females were recruited from three high schools at Taipei for this study (Table 1
). None of these subjects were diabetic based on the American Diabetes Association criteria. The anthropometric measurements, including height, weight, waist and hip circumferences, and blood pressure measurement were performed as described (25). Informed consents were obtained from the subjects and their parents or legal guardians. The survey was reviewed and funded by the National Science Council of Taiwan.
|
A venous blood sample was taken after 12 h of fasting for measuring plasma glucose, TGs, total cholesterol, low-density lipoprotein cholesterol (LDL-C), HDL-C, and insulin as previously described (15). The insulin resistance index derived by homeostasis model assessment (HOMA) was previously described (26). Fasting plasma adiponectin was measured in duplicate with a RIA kit (Linco Research Inc., St. Louis, MO), following the manufacturers protocol. Both the intraassay and interassay coefficients of variation were less than 10%. The values presented were the means of two tests of the same sample.
Statistical analyses
The data are presented as the means and SD unless indicated otherwise. Units of all variables except that of adiponectin were SI unit unless indicated otherwise. Log transformation was performed for variables with significant deviation from normal distribution before further analyses. The correlation analyses in Table 1
and multivariate linear regression analyses in Tables 2
and 3
were also performed. In model 9 of both Tables 2
and 3
, only BMI, insulin, and HDL-C, respectively, representing weight, glucose/insulin, and lipid factors were used to avoid the problem of colinearity. The least square (LS) means of plasma adiponectin levels with the adjustment of age and BMI among the subjects in different quartiles of blood pressures were tested by ANOVA. The mean arterial pressure and pulse pressure were calculated as one third SBP + two thirds DBP and SBP-DBP, respectively. These statistical analyses were performed using the PC version of the Statistical Analysis System (SAS, 6.12 edition, SAS Institute Inc., Cary, NC). P value < 0.05 was considered significant.
|
|
| Results |
|---|
|
|
|---|
In multivariate linear regression analyses, the SBP was significantly related to the plasma adiponectin levels after the adjustment for age or age plus the other anthropometric or metabolic variables as shown in Table 2
. In contrast, the DBP was related significantly only to the plasma adiponectin levels after the adjustment for age or age plus TGs and age plus fasting plasma glucose (Table 3
). The DBP was also related to the plasma adiponectin levels with a borderline significance after adjustment for age plus HDL-C, age plus fasting plasma insulin levels, and age plus insulin resistance index by HOMA (Table 3
). The relation between the plasma adiponectin levels and the SBP, but not the DBP, appeared to be independent of the other anthropometric and metabolic variables among these adolescent females.
Using plasma adiponectin levels as the dependent variable, and age, SBP, BMI, HDL-C, and insulin as independent variables in a multivariate linear regression model, SBP (ß = -0.009 ± 0.004, P = 0.023) and BMI (ß = -0.057 ± 0.016, P = 0.001) were significantly related to the plasma adiponectin levels, whereas HDL-C and insulin were not (data not shown). The age and BMI-adjusted LS means of plasma adiponectin levels among these subjects categorized by the quartiles of the SBP are shown in Fig. 1A
. The LS mean of the plasma adiponectin levels of the lowest SBP quartile (SBP < 100 mm Hg) was significantly different from that of the highest SBP quartile (SBP
118 mm Hg) in an ANOVA model with the adjustment for age and BMI (P = 0.035, Fig. 1A
). The difference of LS means of the plasma adiponectin levels between the lowest and the second highest quartiles (SBP 110117 mm Hg) was of borderline significance (P = 0.055, Fig. 1A
).
|
Using mean arterial pressure (MAP) as a variable in the analyses, we found that the plasma adiponectin levels were significantly correlated with MAP (data not shown). In regression analyses, the plasma adiponectin levels were related to MAP (as the dependent variable) significantly with the adjustment for TG, HDL-C, insulin, or glucose (data not shown) but with only a borderline significance with adjustment for BMI or waist circumference (data not shown). When adjusted for age, BMI, HDL-C, and insulin altogether, the plasma adiponectin levels were not significantly related to the MAP in multivariate linear regression analysis (P = 0.16). In contrast, plasma adiponectin levels were significantly related to pulse pressure with or without adjustment for the other variables (data not shown). When adjusted for age, BMI, HDL-C, and insulin altogether, the plasma adiponectin levels were still significantly related to the pulse pressure (as the dependent variable) in a negative manner in multivariate linear regression analysis (ß= -6.3 ± 3.0, P = 0.038).
| Discussion |
|---|
|
|
|---|
In our previous report, we studied only overweight/obese adults (15). We did not observe any correlation between plasma adiponectin and blood pressure, despite consistent correlation between plasma adiponectin levels with most variables of MS (15). We speculated that it might be hard to demonstrate the relation between blood pressure and plasma adiponectin in a group of adults with multiple metabolic abnormalities (15). We and others (15, 16) have demonstrated in previous reports that the lipid factor appeared to be most strongly related to the levels of plasma adiponectin in adults. The presence of these factors that is probably more intimately related to the plasma adiponectin could obscure the effects of blood pressure. In the article by Kazumi et al. (22), healthy lean college male students were studied. They showed higher plasma adiponectin in subjects with optimal blood pressure (<120/80 mm Hg), even with the adjustment of BMI (22). In this report, we showed a negative relation between plasma adiponectin and blood pressure in a group of healthy nondiabetic female adolescents. We further showed that the relationship between plasma adiponectin and SBP, but not DBP, was independent of the other anthropometric and metabolic variables.
Although not specifically designed to address this issue, Kondo et al. (27) looked at a I164T mutation of the human adiponectin gene associated with extremely low plasma adiponectin levels (0.44.4 µg/ml) in nine Japanese subjects. Interestingly, eight of nine subjects were hypertensive (by SBP
140 mm Hg or DBP
90 mm Hg) (27). Six subjects had both elevated SBP and DBP (27). Two had only elevated SBP (27). Whether the relationship between extreme hypoadiponectinemia and elevated blood pressure is independent of the other anthropometric or metabolic profiles among these subjects is unclear.
The biological mechanisms responsible for the association of hypoadiponectinemia with higher blood pressure are not known at present. Nevertheless, it has been clearly demonstrated that adiponectin influenced the functions of endothelial cells and smooth muscle cells, two main cell types relevant to blood pressure regulation (5, 7, 9, 28, 29). For examples, the recombinant adiponectin attenuated TNF
-induced adhesion molecule expression in cultured human endothelial cells (9, 28). The recombinant adiponectin also reduced platelet-derived growth factor-ßß-induced proliferation and migration of cultured human smooth muscle cells (29). Whether adiponectin may influence the expression and activity of molecules that regulate vasotonicity, such as endothelial nitric oxide synthase, is still unexplored. In adiponectin knockout mice, neointima formation increased after vessel injury (5, 7). The short- and long-term consequences of adiponectin deficiency on blood pressure have not been reported in these animals.
Recently it was demonstrated that androgen but not estrogen suppressed the expression of adiponectin by reducing its secretion (30). We chose female adolescents instead of males for analyses in this report because the effects of androgen around puberty might seriously confound the analyses. In fact, the preliminary analyses of the data from more than 100 male adolescents showed no relationship between plasma adiponectin and blood pressures whatsoever, despite that correlations with the other anthropometric and metabolic variables were still retained (data not shown).
In conclusion, we have demonstrated that the plasma adiponectin levels have an independent negative relation with SBP in female adolescents. This completed the list of the major components of MS in relation to plasma adiponectin and further strengthens the potential roles of adiponectin in the pathophysiology of MS and CAD. Whether adiponectin could be a "common soil" for various phenotypes of MS is an attractive hypothesis to explore. However, our study is a cross-sectional association study and therefore is not capable of addressing this issue. In addition, the relation between plasma adiponectin levels and SBP was observed in healthy nondiabetic female adolescents. Whether the plasma adiponectin levels in adolescence would predict their risk of developing MS in adulthood would require a long-term, follow-up study.
| Acknowledgments |
|---|
| Footnotes |
|---|
Abbreviations: BMI, Body mass index; CAD, coronary artery disease; DBP, diastolic blood pressure; HDL-C, high-density lipoprotein cholesterol; HOMA, homeostasis model assessment; LDL-C, low-density lipoprotein cholesterol; LS, least square; MAP, mean arterial pressure; MS, metabolic syndrome; SBP, systolic blood pressure; TG, triglyceride.
Received January 31, 2003.
Accepted May 15, 2003.
| References |
|---|
|
|
|---|
B signaling through a cAMP-dependent pathway. Circulation 102:12961301This article has been cited by other articles:
![]() |
M. Matsumoto, S. Ishikawa, and E. Kajii Association of Adiponectin With Cerebrovascular Disease: A Nested Case-Control Study Stroke, February 1, 2008; 39(2): 323 - 328. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Fesus, G. Dubrovska, K. Gorzelniak, R. Kluge, Y. Huang, F. C. Luft, and M. Gollasch Adiponectin is a novel humoral vasodilator Cardiovasc Res, September 1, 2007; 75(4): 719 - 727. [Abstract] [Full Text] [PDF] |
||||
![]() |
W.-S. Yang, Y.-C. Yang, C.-L. Chen, I-L. Wu, J.-Y. Lu, F.-H. Lu, T.-Y. Tai, and C.-J. Chang Adiponectin SNP276 is associated with obesity, the metabolic syndrome, and diabetes in the elderly Am. J. Clinical Nutrition, August 1, 2007; 86(2): 509 - 513. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Kadowaki, M. Waguri, I. Nakanishi, Y. Miyashita, M. Nakayama, N. Suehara, T. Funahashi, I. Shimomura, and T. Fujita Adiponectin Concentration in Umbilical Cord Serum Is Positively Associated with the Weight Ratio of Fetus to Placenta J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 5090 - 5094. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. You, R. Yang, M. F. Lyles, D. Gong, and B. J. Nicklas Abdominal adipose tissue cytokine gene expression: relationship to obesity and metabolic risk factors Am J Physiol Endocrinol Metab, April 1, 2005; 288(4): E741 - E747. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. M. Maahs, L. G. Ogden, G. L. Kinney, P. Wadwa, J. K. Snell-Bergeon, D. Dabelea, J. E. Hokanson, J. Ehrlich, R. H. Eckel, and M. Rewers Low Plasma Adiponectin Levels Predict Progression of Coronary Artery Calcification Circulation, February 15, 2005; 111(6): 747 - 753. [Abstract] [Full Text] [PDF] |
||||
![]() |
S G Kim, H Y Kim, J A Seo, K W Lee, J H Oh, N H Kim, K M Choi, S H Baik, and D S Choi Relationship between serum adiponectin concentration, pulse wave velocity and nonalcoholic fatty liver disease Eur. J. Endocrinol., February 1, 2005; 152(2): 225 - 231. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. I. Yilmaz, A. Sonmez, S. Kilic, T. Celik, N. Bingol, M. Pinar, T. Mumcuoglu, and M. Ozata The association of plasma adiponectin levels with hypertensive retinopathy Eur. J. Endocrinol., February 1, 2005; 152(2): 233 - 240. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Bottner, J. Kratzsch, G. Muller, T. M. Kapellen, S. Bluher, E. Keller, M. Bluher, and W. Kiess Gender Differences of Adiponectin Levels Develop during the Progression of Puberty and Are Related to Serum Androgen Levels J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 4053 - 4061. [Abstract] [Full Text] [PDF] |
||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |