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Hypothyroidism and thyroxin substitution affect the n−3 fatty acid composition of rat liver mitochondria

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Lipids

Abstract

The effects of hypothyroidism and of daily treatment for up to 21 days with thyroxin (T4, 0.5 μg/100 g body weight) on the fatty acid composition of total lipid, phosphatidylethanolamine, and phosphatidylcholine of rat liver mitochondria were studied. The fatty acid compositions of hypothyroid and euthyroid (control) rats of similar age were compared. The n−6 and n−3 polyunsaturated fatty acids (PUFA) were affected differently by the hypothyroid state. The levels of linoleic (18∶2n−6), γ-linolenic (18∶3n−6) and dihomo-γ-linolenic acids (20∶3n−6) were higher in hypothyroid rats than in controls, while the level of arachidonic acid (20∶4n−6) was lower, which suggests an impairment of the elongase and desaturase activities. The n−3 polyunsaturated fatty acids, eicosapentaenoic (EPA, 20∶5n−3) and docosapentaenoic (22∶5n−3) acids, were higher in hypothyroid rats, whereas the linolenic acid (18∶3n−3) content remained constant. The level of docosahexaenoic acid (DHA, 22∶6n−3) was dramatically decreased in hypothyroid rats, while the levels of C22 n−6 fatty acids were unchanged. The differences were probably due to the competition between n−3 and n−6 PUFA for desaturases, elongases and acyltransferases. When hypothyroid rats were treated with thyroxin, the changes induced by hypothyroidism in the proportions of n−6 fatty acids were rapidly reversed, while the changes in the n−3 fatty acids were only partially reversed. After 21 days of thyroxin treatments, the DHA content was only half as high in hypothyroid rats than in euthyroid rats. These results suggest that the conversion of 18∶2n−6 to 20∶4n−6 is suppressed in the hypothyroid state which favors the transformation of 18∶3n−3 to 20∶5n−3. The marked decrease in DHA content indicates an impairment of the enzymes involved in the DHA metabolism, possibly the n−3 Δ4 desaturase or the acyltransferases. The increased levels of EPA and 22∶5n−3 is consistent with the inhibition of the n−3 pathway at the Δ4 desaturase step. Observed modifications in the fatty acid composition may significantly alter eicosanoid synthesis and membrane functions in hypothyroidism.

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Abbreviations

AA:

arachidonic acid, 20∶4n−6

DHA:

docosahexaenoic acid, 22∶6n−3

DPA:

docosapentaenoic acid, 22∶5n−3

EFA:

essential fatty acid

EPA:

eicosapentaenoic acid, 20∶5n−3

FAME:

fatty acid methyl ester

PC:

phosphatidylcholine

PE:

phosphatidylethanolamine

PUFA:

polyunsaturated fatty acid(s)

SEM:

standard error of the mean

T3:

3,3′,5-triiodothyronine

T4:

3,3′,5,5′-tetraiodothyronine, thyroxin

UI:

unsaturation index

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Author notes

  1. C. A. Meier

    Present address: NIDDK, MCNEB, National Institutes of Health, 20892, Bethesda, MD

Authors and Affiliations

  1. Department of Vitamin and Nutrition Research, F. Hoffmann-La Roche Ltd., VFRB B. 60/317A, CH-4002, Basel, Switzerland

    D. Raederstorff & U. Moser

  2. Department of Biochemistry, University of Basel, CH-4051, Basel, Switzerland

    C. A. Meier & P. Walter

Authors
  1. D. Raederstorff
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  2. C. A. Meier
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  3. U. Moser
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  4. P. Walter
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Raederstorff, D., Meier, C.A., Moser, U. et al. Hypothyroidism and thyroxin substitution affect the n−3 fatty acid composition of rat liver mitochondria. Lipids 26, 781–787 (1991). https://doi.org/10.1007/BF02536158

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  • DOI: https://doi.org/10.1007/BF02536158

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