Subclinical hypothyroidism and hyperthyroidism have opposite effects on hepatic very-low-density lipoprotein-triglyceride kinetics
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Subclinical hypothyroidism and hyperthyroidism have opposite effects on hepatic very-low-density lipoprotein-triglyceride kinetics. / Fabbrini, Elisa; Magkos, Faidon; Patterson, Bruce W; Mittendorfer, Bettina; Klein, Samuel.
I: Journal of Clinical Endocrinology and Metabolism, Bind 97, Nr. 3, 2012, s. E414-E418.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Subclinical hypothyroidism and hyperthyroidism have opposite effects on hepatic very-low-density lipoprotein-triglyceride kinetics
AU - Fabbrini, Elisa
AU - Magkos, Faidon
AU - Patterson, Bruce W
AU - Mittendorfer, Bettina
AU - Klein, Samuel
N1 - (Ekstern)
PY - 2012
Y1 - 2012
N2 - Context: Clinically overt thyroid dysfunction is associated with alterations in triglyceride (TG) metabolism. The effect of subclinical thyroid disease on very-low-density lipoprotein (VLDL) kinetics is not known.Objective: Our objective was to investigate whether subclinical thyroid disease is associated with alterations in hepatic VLDL metabolism. DESIGN AND Outcomes: We measured VLDL-TG and VLDL-apolipoprotein B-100 (apoB-100) kinetics by infusing stable isotopically labeled tracers, in conjunction with mathematical modeling.Setting and participants: Ten women with subclinical hypothyroidism, 10 women with subclinical hyperthyroidism, and 25 euthyroid women, matched on age, body mass index, and percent body fat, were studied in the Clinical Research Unit at Washington University School of Medicine.Results: Plasma VLDL-TG concentrations were 0.75±0.13, 0.51±0.06, and 0.37±0.07 mmol/liter (P=0.029), and hepatic VLDL-TG secretion rates were 6.5±0.7, 5.0±0.4, and 4.1±0.6 μmol/liter·min (P=0.026) in hypothyroid, euthyroid, and hyperthyroid women, respectively. The differences in VLDL-TG secretion rates were due to differences in the incorporation of systemic plasma free fatty acids into VLDL-TG (4.3±0.3, 3.1±0.3, and 2.5±0.3 μmol/liter·min in hypothyroid, euthyroid, and hyperthyroid women, respectively; P=0.005). Plasma VLDL-apoB-100 concentration and hepatic secretion rate did not differ among groups (P>0.400), so the molar ratios of VLDL-TG to VLDL-apoB-100 secretion rates were 21,469±3,477, 16,025±1,273, and 11,889±1,319 in hypothyroid, euthyroid, and hyperthyroid women, respectively (P=0.019).Conclusions: Subclinical thyroid disease affects hepatic VLDL-TG but not VLDL-apoB-100 metabolism: subclinical hypothyroidism increases, whereas subclinical hyperthyroidism decreases, hepatic VLDL-TG secretion rate compared with the euthyroid state. Plasma VLDL-TG concentration is greater in subclinical hypothyroid than euthyroid and hyperthyroid subjects, due to greater secretion of large, TG-rich VLDL particles from the liver.
AB - Context: Clinically overt thyroid dysfunction is associated with alterations in triglyceride (TG) metabolism. The effect of subclinical thyroid disease on very-low-density lipoprotein (VLDL) kinetics is not known.Objective: Our objective was to investigate whether subclinical thyroid disease is associated with alterations in hepatic VLDL metabolism. DESIGN AND Outcomes: We measured VLDL-TG and VLDL-apolipoprotein B-100 (apoB-100) kinetics by infusing stable isotopically labeled tracers, in conjunction with mathematical modeling.Setting and participants: Ten women with subclinical hypothyroidism, 10 women with subclinical hyperthyroidism, and 25 euthyroid women, matched on age, body mass index, and percent body fat, were studied in the Clinical Research Unit at Washington University School of Medicine.Results: Plasma VLDL-TG concentrations were 0.75±0.13, 0.51±0.06, and 0.37±0.07 mmol/liter (P=0.029), and hepatic VLDL-TG secretion rates were 6.5±0.7, 5.0±0.4, and 4.1±0.6 μmol/liter·min (P=0.026) in hypothyroid, euthyroid, and hyperthyroid women, respectively. The differences in VLDL-TG secretion rates were due to differences in the incorporation of systemic plasma free fatty acids into VLDL-TG (4.3±0.3, 3.1±0.3, and 2.5±0.3 μmol/liter·min in hypothyroid, euthyroid, and hyperthyroid women, respectively; P=0.005). Plasma VLDL-apoB-100 concentration and hepatic secretion rate did not differ among groups (P>0.400), so the molar ratios of VLDL-TG to VLDL-apoB-100 secretion rates were 21,469±3,477, 16,025±1,273, and 11,889±1,319 in hypothyroid, euthyroid, and hyperthyroid women, respectively (P=0.019).Conclusions: Subclinical thyroid disease affects hepatic VLDL-TG but not VLDL-apoB-100 metabolism: subclinical hypothyroidism increases, whereas subclinical hyperthyroidism decreases, hepatic VLDL-TG secretion rate compared with the euthyroid state. Plasma VLDL-TG concentration is greater in subclinical hypothyroid than euthyroid and hyperthyroid subjects, due to greater secretion of large, TG-rich VLDL particles from the liver.
KW - Adult
KW - Apolipoprotein B-100/metabolism
KW - Female
KW - Humans
KW - Hyperthyroidism/metabolism
KW - Hypothyroidism/metabolism
KW - Lipoproteins, VLDL/metabolism
KW - Liver/metabolism
KW - Triglycerides/metabolism
U2 - 10.1210/jc.2011-2777
DO - 10.1210/jc.2011-2777
M3 - Journal article
C2 - 22238397
VL - 97
SP - E414-E418
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 3
ER -
ID: 290035724