ACLS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Choi, J. W.
Right arrow Articles by Pai, S. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Choi, J. W.
Right arrow Articles by Pai, S. H.
Annals of Clinical & Laboratory Science 34:400-404 (2004)
© 2004 Association of Clinical Scientists

Brief Communication

Associations of Serum TRAIL Concentrations, Anthropometric Variables, and Serum Lipid Parameters in Healthy Adults

Jong Weon Choi1, Jung Soo Song2 and Soo Hwan Pai1
1 Department of Laboratory Medicine and 2 Department of Rheumatology/Medicine, College of Medicine, Inha University, Inchon, South Korea

Address correspondence to Soo Hwan Pai, M.D., Department of Laboratory Medicine, Inha University Hospital, 7-206, 3-ga, Shinheung-dong, Jung-gu, Inchon, 400-711, South Korea; tel 82 32 890 2503; fax 82 32 890 2529; e-mail shpaimd{at}inha.ac.kr.

Abstract

To investigate the relationships of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), anthropometric variables, and lipid parameters, we measured serum TRAIL concentrations, body mass index (BMI), total body fat (TBF), and serum lipid profiles in 207 healthy adults. There were no significant differences in serum TRAIL concentrations between men and women, nor between elderly persons and middle-aged subjects. However, men with TBF 16.4 kg (75th per centile) exhibited significantly higher serum TRAIL concentrations than those with TBF 11.2 kg (25th per centile) (69.7 ± 15.1 pg/ml vs 50.2 ± 14.3 pg/ml, p <0.05). Serum TRAIL concentration averaged 76.2 ± 16.1 pg/ml in women with low-density lipoprotein cholesterol (LDL-C) 165 mg/dl (75th per centile), which was significantly above the values (53.1 ± 12.9 pg/ml, p <0.05) in those with LDL-C 117 mg/dl (25th per centile), although no differences were observed on the basis of TBF (75th percentile vs 25th percentile). Serum TRAIL concentrations correlated significantly with TBF (r = 0.31, p <0.05) and lean body mass (r = –0.26, p <0.05) in men and LDL-C (r = 0.32, p <0.05) and total cholesterol (r = 0.21, p <0.05) in women. In conclusion, serum TRAIL concentrations are associated with serum lipid levels and body adiposity in healthy adults, but are unrelated to a subject’s age or gender.

(received 30 June 2004; accepted 2 August 2004)

Keywords: tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), total body fat, serum lipid levels, low-density lipoprotein cholesterol

Introduction

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a TNF superfamily member [1,2]. TRAIL is transmembrane protein expressed on cell surfaces and has a broad expression pattern in a variety of organs [3]. TRAIL is capable of inducing apoptosis in lymphoid and non-lymphoid tumor cell lines, thus providing an exciting prospect for development of therapeutic strategies in cancer [4]. In normal physiology, TRAIL is thought to act in tumor suppression and immune cell homeostasis, and also to play a role in viral-induced diseases [5].

Obesity is a condition with abnormally increased body fat, resulting from increased energy intake relative to energy expenditure. Numerous epidemiological studies have shown that obesity is directly associated with the risk of cancer at several organ sites, including colon, breast, and endometrium [6,7]. These associations with cancer risk are explained by alterations in steroid hormone and insulin-like growth factor levels, which can lead to distortion of the normal balance between cell proliferation, differentiation, and apoptosis [8]. Increased serum lipid levels have been reported to be significantly associated with apoptosis in animal studies [9,10]. Some investigators demonstrated that TNF-{alpha} plays an important role in multiple aspects of adipose tissue biology and mediates the abnormalities that occur at this site in obesity [11]. Despite intense research, data for the changes in serum TRAIL concentrations in healthy subjects, especially in relation to body adiposity and serum lipid profiles, are limited. In the present study, we tested whether serum TRAIL concentration correlates significantly with total body fat (TBF), body mass index (BMI), and serum lipid concentrations. We also investigated whether serum TRAIL concentrations change with subjects’ age and gender in apparently healthy individuals.

Materials and Methods

A total of 207 adults (91 men, 116 women) with a median age of 61 yr (range 50–72 yr) were investigated by measurements of serum TRAIL concentrations and serum lipid profiles, including total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). To minimize the influence of age and hormonal effects on serum lipid levels and TBF, only postmenopausal women and age-matched men were enrolled in this study. The women were judged to have reached menopause if they had not menstruated for 12 mo prior to the inv estigation. Five subjects with postmenopausal hormone replacement therapy (n = 3) or acute and chronic diseases (n = 2) were excluded from study.

Four anthropometric parameters were measured in all subjects. The anthropometric indices included body weight, height, waist-to-hip ratio (WHR), and BMI (kg/m2). Body fat and lean body mass were assessed using a 8-polar tactile-electrode impedance-meter (body composition analyzer, InBody 3.0, Biospace Inc, Seoul, Korea), as described previously [12]. The subjects were all Korean, with no significant differences in race or socioeconomic status among the groups. The study was approved by the Ethics Committee of Inha University Hospital; informed consent was obtained from all subjects.

After the subjects had fasted for >12 hr, venous blood was drawn into an evacuated serum separator tube. Serum TRAIL concentrations were measured by an enzyme immunoassay (Quantikine human TRAIL/TNFSF10 kit, R&D Systems Inc, Minneapolis, MN, USA). Serum lipid profiles were assayed with an automatic chemical analyzer (Hitachi 747, Hitachi Corp, Tokyo, Japan) within 4 hr after collection. Serum triglyceride, total cholesterol, HDL-C, and LDL-C concentrations were analyzed by enzymatic colorimetric methods using triglyceride GPO-PAP reagents (Roche Diagnostics GmbH, Mannheim, Germany), SICDIA L T-CHO reagents (Eiken Chemical Industries, Tokyo, Japan), Cholestest-HDL reagents (Daiichi Chemicals, Tokyo, Japan), and Cholestest-LDL reagents (Daiichi Chemicals), respectively.

To investigate differences in serum TRAIL concentrations in relation to subjects’ age and gender, the subjects were assigned to 4 groups: men and women 50–55 yr of age (median age, 53 yr, n = 52), 56–60 yr (median age, 57 yr, n = 58), 61–65 yr (median age, 62 yr, n = 50), and >65 yr (median age, 69 yr, n = 47), respectively. The subject population was also divided into 2 groups: women in one group; men in the other group. This was done according to the values of TBF and LDL-C: men with TBF 16.4 kg (75th per centile; n = 23) and TBF 11.2 kg (25th per centile; n = 23); women with LDL-C 165 mg/dl (75th per centile; n = 29) and LDL-C 117 mg/dl (25th per centile; n = 29).

Data analysis was performed with the SAS software package (SAS Institute, Cary, NC, USA). A non-parametric test (Wilcoxon rank sum test) was used to test the statistical significance of inter-group differences. Correlation coefficients were calculated by the Spearman method. All p values <0.05 were considered statistically significant.

Results and Discussion

In this study, we investigated the relationships of anthropometric variables, body composition, and serum lipid parameters vs serum TRAIL concentrations in healthy adults. We found that serum TRAIL concentrations are closely associated with body composition and serum lipid levels, especially TBF in men and LDL-C in women. Mean values of serum TRAIL concentrations in the subjects are summarized in Table 1Go. Women showed a propensity towards slightly higher values of serum TRAIL concentrations compared to men, but this trend was not statistically significant. No differences were observed in serum TRAIL concentrations between persons >65 yr and subjects 50–55 yr of age. These results suggest that subjects’ age or gender do not significantly influence serum TRAIL concentrations, at least in individuals >50 yr of age.


View this table:
[in this window]
[in a new window]
  		Table 1. Mean values of serum TRAIL concentrations in relation to age and gender in healthy Korean adults.
 
To investigate the change in serum TRAIL concentrations according to serum lipid levels and TBF, the subjects with increased TBF or LDL-C concentrations were compared to those with decreased values of these parameters. There were no significant differences in TRAIL concentrations between the 2 groups, based on the mean values of LDL-C (135.2 mg/dl in men; 145.0 mg/dl in women) and TBF (14.7 kg in men; 20.1 kg in women) of the subject populations, which were taken as the provisional cutoff levels in this study. However, large differences in serum TRAIL concentrations were noted when the subjects with elevated values (75th percentile) of LDL-C or TBF were compared to those with lowered levels (25th percentile) of LDL-C or TBF (Tables 2Go and 3Go). The mean value of serum TRAIL was 69.7 ± 15.1 pg/ml in men with TBF 16.4 kg (75th per centile), which was significantly higher than in those with TBF 11.2 kg (25th per centile) (50.2 ± 14.3 pg/ml, p <0.05), although no significant differences were detected on the basis of serum LDL-C concentrations (75th percentile vs 25th percentile).


View this table:
[in this window]
[in a new window]
  		Table 2. Serum TRAIL levels, anthropometric variables, and serum lipid profiles in relation to total body fat in male subjects.
 

View this table:
[in this window]
[in a new window]
  		Table 3. Serum TRAIL levels, anthropometric variables, and serum lipid profiles in relation to LDL-cholesterol levels in post-menopausal women.
 
In postmenopausal women, subjects with LDL-C 165 mg/dl (75th per centile) showed significantly higher serum TRAIL concentrations (76.2 ± 16.1 pg/ml) than those with LDL-C 117 mg/dl (25th percentile) (53.1 ± 12.9 pg/ml, p <0.05), but no significant differences were observed when the results were based on the values of TBF (75th percentile vs 25th percentile). As shown in Table 4Go, serum TRAIL concentrations had weak but significant correlations with TBF (r = 0.31, p <0.05), WHR (r = 0.25, p <0.05), and lean body mass (r = –0.26, p <0.05) in men, and also had positive correlations with total cholesterol (r = 0.21, p <0.05) and LDL-C (r = 0.32, p <0.05) in women. These results suggest that serum TRAIL concentrations are closely associated with serum lipid levels and body composition, especially if LDL-C or TBF are moderately elevated.


View this table:
[in this window]
[in a new window]
  		Table 4. Correlation coefficients of anthropometric parameters and lipid profiles vs serum TRAIL concentrations in 207 subjects.
 
Apoptosis is a mode of cell death in which single cells are deleted in the midst of living tissue. Apoptosis accounts for most or all of the programmed cell death responsible for tissue remodeling and atrophy, and for the physiologic death of cells in the course of normal tissue turnover [13]. Considering that both cell-surface and soluble TRAIL trigger apoptosis in susceptible cells by activating respective receptors [14], the elevated serum TRAIL concentrations that were observed in some elderly persons with increased LDL-C or TBF imply that apoptosis occurs more actively in the subjects with elevated LDL-C or TBF than in those with lowered values in LDL-C or TBF. These results support the data of several investigators who found that apoptosis is increased in animal models during experimental hypercholesterolemia [15,16].

In conclusion, serum TRAIL concentrations showed significant correlations with serum LDL-C and TBF in men and women 50 yr of age, suggesting that the expression of soluble TRAIL may be related to lipid metabolism in elderly persons. Serum TRAIL level does not seem to differ according to age or gender in healthy adults. Further experiments regarding TRAIL receptors and apoptosis may explain why serum TRAIL concentrations correlate with TBF and LDL-C in elderly persons.

Acknowledgement

This study was supported by a research grant from the Medical Association of Inchon Metropolitan City in the Republic of Korea.

References

  1. Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 1995;3:673–682.[Medline]
  2. Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray CL, Baker K, Wood WI, Goddard AD, Godowski P, Ashkenazi A. Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 1997;277:818–821.[Abstract/Free Full Text]
  3. Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A, Ashkenazi A. Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem 1996;271:12687–12690.[Abstract/Free Full Text]
  4. Tsokos GC, Tsokos M. The TRAIL to arthritis. J Clin Invest 2003;112:1315–1317.[Medline]
  5. Baetu TM, Hiscott J. On the TRAIL to apoptosis. Cytokine Growth Factor Rev 2002;13:199–207.[Medline]
  6. Lubin F, Ruder AM, Wax Y, Modan B. Overweight and changes in weight throughout adult life in breast cancer etiology. A case-control study. Am J Epidemiol 1985; 122:579–588.[Abstract/Free Full Text]
  7. Bianchini F, Kaaks R, Vainio H. Overweight, obesity, and cancer risk. Lancet Oncol 2002;3:565–574.[Medline]
  8. Suga K, Imai K, Eguchi H, Hayashi S, Higashi Y, Nakachi K. Molecular significance of excess body weight in postmenopausal breast cancer patients, in relation to expression of insulin-like growth factor I receptor and insulin-like growth factor II genes. Jpn J Cancer Res 2001;92:127–134.
  9. Inoue K, Kubota S, Seyama Y. Cholestanol induces apoptosis of cerebellar neuronal cells. Biochem Biophys Res Commun 1999;256:198–203.[Medline]
  10. Simabukuro M, Zhou YT, Levi M, Unger RH. Fatty acid-induced beta cell apoptosis: a link between obesity and diabetes. PNAS USA 1998;95:2498–2502.[Abstract/Free Full Text]
  11. Nisoli E, Briscini L, Giordano A, Tonello C, Wiesbrock SM, Uysal KT, Cinti S, Carruba MO, Hotamisligil GS. Tumor necrosis factor alpha mediates apoptosis of brown adipocytes and defective brown adipocyte function in obesity. PNAS USA 2000;97:8033–8038.[Abstract/Free Full Text]
  12. Choi JW. Association between elevated serum hepatic enzyme activity and total body fat in obese humans. Ann Clin Lab Sci 2003;33:257–264.[Abstract/Free Full Text]
  13. Wyllie AH. Apoptosis and the regulation of cell numbers in normal and neoplastic tissues: an overview. Cancer Metastasis Rev 1992;11:95–103.[Medline]
  14. Mitsiades CS, Poulaki V, Mitsiades N. The role of apoptosis-inducing receptors of the tumor necrosis factor family in thyroid cancer. J Endocrinol 2003;178:205–216.[Abstract]
  15. Rajamannan NM, Sangiorgi G, Springett M, Arnold K, Mohacsi T, Spagnoli LG, Edwards WD, Tajik AJ, Schwartz RS. Experimental hypercholesterolemia induces apoptosis in the aortic valve. J Heart Valve Dis 2001; 10:371–374.[Medline]
  16. Hasdai D, Sangiorgi G, Spagnoli LG, Simari RD, Holmes DR Jr, Kwon HM, Carlson PJ, Schwartz RS, Lerman A. Coronary artery apoptosis in experimental hypercholesterolemia. Atherosclerosis 1999;142:317–325.[Medline]



This article has been cited by other articles:


Home page
 Am J Clin NutrHome page
V. S. Voruganti, S. A. Cole, S. O. Ebbesson, H. H. Goring, K. Haack, S. Laston, C. R. Wenger, M. E. Tejero, R. B. Devereux, R. R. Fabsitz, et al.
Genetic variation in APOJ, LPL, and TNFRSF10B affects plasma fatty acid distribution in Alaskan Eskimos
Am J Clin Nutr, June 1, 2010; 91(6): 1574 - 1583.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
I. Mader, M. Wabitsch, K. M. Debatin, P. Fischer-Posovszky, and S. Fulda
Identification of a novel proapoptotic function of resveratrol in fat cells: SIRT1-independent sensitization to TRAIL-induced apoptosis
FASEB J, June 1, 2010; 24(6): 1997 - 2009.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Choi, J. W.
Right arrow Articles by Pai, S. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Choi, J. W.
Right arrow Articles by Pai, S. H.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS