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

Abstract

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.

Roux-en-Y gastric bypass and calorie restriction induce comparable time-dependent effects on thyroid hormone function tests in obese female subjects

“…Chronic overnutrition is suggested to decrease rT 3 catabolism through enhanced peripheral D1 expression and reduced peripheral D2 expression (22). However, decreased D2 activity is unlikely, as we also observed increased T 3 levels.…”

Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats

“…A mixed high-fat diet resulted in elevated serum TSH with normal serum T3 and T4 levels in a study conducted by Araujo RL [15] , whereas timedependent decreases in serum TT3 and TT4 were observed according to Han et al [16] . The different high-fat compositions in the two studies may underlie the inconsistent results.…”

Chronic AMP-kinase activation with AICAR reduces adiposity by remodeling adipocyte metabolism and increasing leptin sensitivity

“…The Comprehensive Laboratory Animal Monitoring System (CLAMS; Columbus Instruments, Inc., Columbus, OH) was used to perform all automated in vivo determinations as previously described ( 14 ). Briefl y, the CLAMS measures oxygen consumption (VO 2 ), carbon dioxide production (VCO 2 ), and respiratory exchange ratio (RER).…”

“…Animals were placed in the CLAMS at 10:00 immediately following the daily saline or AICAR injections. The fi rst hour of data collected in the CLAMS was discarded, because it is the time required for the rats to fully acclimatize to the cage environment ( 14 ). The rats were monitored for a 24 h period encompassing the light (10:00-19:00 and 07:00-10:00) and dark (19:00-07:00) cycles.…”

“…Weights of all tissues were normalized per 100g of body weight. Lean body mass (LBM) was calculated as carcass weight with all skin, viscera, and fat depots removed ( 14 ).…”