High-fat diet increases thyrotropin and oxygen consumption without altering circulating 3,5,3'-triiodothyronine (T3) and thyroxine in rats: the role of iodothyronine deiodinases, reverse T3 production, and whole-body fat oxidation.
This study investigated the effects of obesity induced by high-fat (HF) diet on thyroid function and whole-body energy balance. To accomplish that, we assessed the effects of 8 wk of HF diet on several parameters of hypothalamus-pituitary-thyroid axis function. Serum total T(4) and T(3), rT(3), and TSH, the activity of type 1 and type 2 deiodinases in central and peripheral tissues were determined. Also, we measured in vivo energy balance, substrate partitioning, and markers of leptin resistance. Here we provide novel evidence that prolonged positive energy balance acquired by feeding a HF diet induced hyperactivation of the hypothalamus-pituitary-thyroid axis, which was characterized by 2.24-, 1.6-, and 3.7-fold elevations in hypothalamic TRH expression, thyroid iodide uptake, and serum TSH, respectively. Serum T(4) and T(3) were normal together with augmented deiodinase type 1 activity in liver (1.3-fold) and kidney (1.2-fold) and increased (1.5-fold) serum rT3 in HF rats. Despite no increase in circulating levels of T(3) and T(4), whole-body oxygen consumption was increased, and substrate metabolism was shifted toward fat oxidation in HF rats. These in vivo metabolic adjustments were mainly driven by the fat content of the diet. Furthermore, spontaneous dark cycle physical activity was reduced by 30% in rats fed a HF diet, which limited energy expenditure and favored the development of obesity. Our findings provide new insight into the endocrine and physiological mechanisms that underlie the alterations in thyroid hormone availability, energy balance, and metabolic partitioning in HF diet-induced obesity.
Araujo
R L
RL
Muscle Health Research Center, School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, Ontario, Canada M3J 1P3.
Andrade
B M
BM
Padrón
A S
AS
Gaidhu
M P
MP
Perry
R L S
RL
Carvalho
D P
DP
Ceddia
R B
RB
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001823:Body Composition / Q000187:drug effects / Q000235:genetics; D004041:Dietary Fats / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D005951:Glucose Tolerance Test; D007453:Iodide Peroxidase / Q000378:metabolism*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D051381:Rats; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood*
D004041:Dietary Fats; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014284:Triiodothyronine; D013972:Thyrotropin; D007453:Iodide Peroxidase; D055372:AMP-Activated Protein Kinases; D013974:Thyroxine