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Letter to the Editor |
Laboratory Clinical Chemistry, University Hospital Ghent 2P8, 9000 Ghent, Belgium
Address correspondence to: Dr. Youri E. C. Taes, Laboratory Clinical Chemistry, University Hospital Ghent 2P8, De Pintelaan 185, 9000 Ghent, Belgium. E-mail: youri.taes{at}Ugent.be.
To the editor:
In their recent article in JCEM, Chiellini et al. (1) reported on the use of serum haptoglobin (Hp) concentration as a marker for adiposity, due to extrahepatic Hp synthesis in adipose tissue. However, some critical remarks can be made, favoring an alternative explanation for these findings.
The association of serum Hp concentration and body mass index (BMI) is not a novel finding. Our group (2) already described a significant association between BMI and serum inflammatory markers: C-reactive protein, fibrinogen, serum amyloid A, and Hp. Hepatic synthesis of these markers is induced by circulating cytokines (predominantly IL-6 for Hp). IL-6 synthesis by adipose tissue is well described. Because serum Hp concentrations are relatively high (0.3–2.0 g/liter) and Hp turnover rate (3) is high (biological half-life, 5.4 d), the contribution of Hp synthesis in adipose tissue to the serum Hp concentration seems only marginal. Important protein synthesis takes place in adipose tissue; however, the fat-derived proteins (adipokines) circulate in plasma in 102-103 lower concentrations than Hp. The liver is the predominant site of Hp synthesis, and the contribution of extrahepatic synthesis to the serum Hp concentration seems limited. Our finding (2) of an association between BMI and several inflammatory markers (C-reactive protein, fibrinogen, serum amyloid A, and Hp) supports the IL-6 mediated hepatic synthesis. Based on these data, adipocyte secretion of IL-6 and subsequent hepatic synthesis of Hp is a more plausible explanation for the observed relationship between adipose mass and Hp concentration.
Secondly, Hp has three major phenotypes (1-1, 2-1, and 2-2). Serum Hp concentrations strongly depend on the Hp phenotype (3). In our study population (2), Hp phenotype accounted for 11% of the variation in Hp concentrations. Moreover, differences in inflammatory status have been described between Hp phenotypes. Hp 2-2 phenotypes showed higher oxidized low-density lipoprotein concentrations, compared with other phenotypes, suggesting a higher oxidative stress in Hp 2-2 phenotypes (4). The relationship of Hp to BMI could have been influenced by differences in inflammatory status between phenotypes. Phenotypic differences could have influenced the present findings and should be taken into account when studying biological effects of Hp.
Moreover the reported Hp concentrations are high in the presented study (1). Global standardization of serum Hp concentration has been implemented worldwide since 1994, as with other serum proteins by the introduction of the CRM470 standard. The accepted reference range of Hp varies between 0.3 and 2.0 g/liter. Unfortunately, no standardization was communicated in the report by Chiellini et al. (1). These Hp concentrations are higher than the reference range and the reported values in large studies (3). This suggests that the used assay has not been calibrated against the CRM470 standard.
In conclusion, care should be taken in interpreting serum Hp concentrations in epidemiological studies due to the IL-6 driven Hp synthesis and the phenotypic dependency of Hp concentrations.
Received October 14, 2004.
References
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