Health aspects of oxidized dietary fats - Oxidation in Foods and Beverages and Antioxidant Applications - page 157

into the thyrocyte (Dai et al., 1996), was reduced, whereas that of thyroid
peroxidase (TPO) increased in the thyroid glands of these rats (Skufca et al.,
2003). TPO catalyzes the transformation of iodide to iodine and is involved in
the iodination of thyroglobulin and the coupling reaction leading to thyroxine
formation (Ekholm, 1981). Although NIS was down-regulated by oxidized fat,
the increased gene expression of TPO is also indicative of a stimulatory effect of
oxidized fat on thyroid function, because TPO but also NIS are regulated on the
transcriptional level by thyrotropin (TSH), which is the most important regulator
of thyroid hormone function (SchrÈder-van der Elst et al., 2001; Riedel et al.,
2001; Damante et al., 1989). However, because the concentration of TSH was
not different between rats fed oxidized fat and those fed fresh fat (Skufca et al.,
2003), it is likely that the effect of the oxidized fat on the thyroid gland was not
mediated by TSH. Since the study from Skufca et al. (2003) clearly showed that
the alteration of thyroid function by oxidized fat is not due to an interaction with
the metabolism of iodine, which is a key nutrient for the formation of thyroid
hormones (Riesco et al., 1976), it has been suggested that lipid peroxidation
products of the diet directly influence the expression of genes involved in
thyroid hormone synthesis.
In an attempt to identify the components responsible for the effects of
oxidized fat on thyroid function and the mechanisms underlying the alterations
in thyroid function by oxidized fat, a recent study investigated the effect of a
primary lipid peroxidation product, namely 13-HPODE ± the quantitatively most
important primary oxidation product of linoleic acid (Niki et al., 2005), and a
characteristic compound of fats heated at moderate temperatures (< 100 ëC) ± on
the function of primary porcine thyrocytes (Luci et al., 2006a). Unexpectedly,
the study from Luci et al. (2006a) failed to demonstrate an important role of 13-
HPODE as a mediator of the alterations of thyroid function observed with
oxidized fats. For instance, Luci et al. (2006a) showed that incubation of porcine
thyrocytes with 13-HPODE did not lead to alterations in gene expression of NIS
and TPO or iodide uptake, even in non-physiologic high concentrations of 100
M. In addition, gene expression of the TSH receptor was also not influenced by
13-HPODE suggesting that it also does not influence the effect of TSH on the
function of porcine thyrocytes.
Luci et al. (2006a), moreover, showed that 13-HPODE leads to a down-
regulation of dual oxidase 2 (DUOX2), which, like NIS and TPO, is involved in
thyroid hormone synthesis by acting as a subunit of NADPH-oxidase (the major
generator of H 2 O 2 in thyrocytes (Moreno et al., 2002)), and to a reduced release
of hydrogen peroxide (Corvilain et al., 1991). Although the authors of this study
did not measure the activity of NADPH oxidase, they suggested that the reduced
gene expression of DUOX2 might be associated with a reduced activity of this
enzyme. The authors, moreover, suggested that the reduced concentrations of
H 2 O 2 in the cells and in the cell medium could be due to an increased activity of
GPx observed in cells treated with 13-HPODE. GPx protects thyrocytes against
a high intracellular concentration of H 2 O 2 , which for instance can lead to
apoptosis (Demelash et al., 2004). It has been postulated that GPx in thyrocytes