Triiodothyronine and leptin repletion in humans similarly reverse weight-loss-induced changes in skeletal muscle (original) (raw)
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Thyroid, 2014
Background: Thyroid hormones are important determinants of energy expenditure, and in rodents, adipose tissue affects thyroid hormone homeostasis via leptin signaling. The relationship between thyroid hormones and nutritional status in humans has been assessed primarily in drastic dietary or bariatric surgery interventions, while limited information is available on serial assessment of this axis during moderate, prolonged dietary restriction. Methods: To evaluate the effects of moderate dietary restriction on thyroid hormone homeostasis, 47 subjects with a body mass index (BMI) of 25-45 kg/m 2 were enrolled in a longitudinal intervention study; 30 nonoverweight volunteers were also enrolled as controls. Overweight and obese subjects underwent a 12-month individualized dietary intervention aimed at achieving a 5-10% weight loss. Results: The intervention resulted in a 6.3 -0.9 kg (6.5 -1.0%) weight loss. At baseline, thyrotropin (TSH) and T3 concentrations correlated significantly with fat mass (R = 0.257, p = 0.024 and R = 0.318, p = 0.005, respectively). After weight loss, T3 decreased significantly (from 112.7 -3.1 to 101.8 -2.6 ng/dL, p < 0.001) in the absence of significant changes in TSH or free T4 (fT4). The decrease in serum T3 correlated with the decrease in weight (R = 0.294, p < 0.001). The T3:fT4 ratio decreased significantly ( p = 0.02) in individuals who lost > 5% body weight. Conclusions: T3 concentration closely correlates with individual nutritional status, and moderate weight loss results in a decrease in T3 with minimal changes in other thyroid hormone homeostasis parameters. The data suggest that a decrease in peripheral conversion of the prohormone T4 into its hormonally active metabolite T3 is at least in part responsible for the observed changes in thyroid hormone homeostasis.
Rejuvenation Research, 2008
Caloric restriction (CR) decreases circulating triiodothyronine (T 3 ) concentration. However, it is not known if this effect is due to body fat mass reductions or due to CR, per se. The purpose of this study was to test the hypothesis that plasma T 3 concentration decreases with CR-induced reductions in fat mass but not in response to similar decreases in fat mass that are induced by exercise. Sedentary, nonobese 50-to 60-year-old men and women with no clinical evidence of cardiovascular or metabolic disease and not taking thyroid medications were randomly assigned to 12 months of caloric restriction (n ϭ 18) or exercise-induced weight loss (n ϭ 17) or to a control group (n ϭ 9). Body weight and composition and plasma concentrations of the thyroid hormones T 3 , thyrotropin (TSH), thyroxine (T 4 ), and free thyroxine (FT 4 ) were measured at baseline and 12 months. Fat mass changed significantly in the CR (Ϫ6.3 Ϯ 1.0 kg) and exercise (Ϫ5.5 Ϯ 1.0 kg) groups but not in the control group (Ϫ0.6 Ϯ 1.4 kg). The changes were not significantly different between the CR and exercise groups. Plasma T 3 concentration decreased in the CR group (Ϫ9.8 Ϯ 2.0 ng/dL, p Ͻ 0.0001) but not in the exercise (Ϫ3.8 Ϯ 2.1 ng/dL, p ϭ 0.07) or control (Ϫ1.3 Ϯ 2.8 ng/dL, p ϭ 0.65) groups. TSH, T 4 , and FT 4 did not change in any of the study groups. Twelve months of CR decreased circulating T 3 concentrations in middle-aged adults. This effect does not appear to be attributable to changes in body fat mass because a comparable decrease in T 3 concentration was not observed in response to an exercise-induced fat mass reduction.
Maintenance of a reduced body weight is accompanied by decreased energy expenditure that is due largely to increased skeletal muscle work efficiency. In addition, decreased sympathetic nervous system tone and circulating concentrations of leptin, thyroxine, and triiodothyronine act coordinately to favor weight regain. These "weight-reduced" phenotypes are similar to those of leptin-deficient humans and rodents. We examined metabolic, autonomic, and neuroendocrine phenotypes in 10 inpatient subjects (5 males, 5 females [3 never-obese, 7 obese]) under 3 sets of experimental conditions: (a) maintaining usual weight by ingesting a liquid formula diet; (b) maintaining a 10% reduced weight by ingesting a liquid formula diet; and (c) receiving twice-daily subcutaneous doses of leptin sufficient to restore 8 am circulating leptin concentrations to pre-weight-loss levels and remaining on the same liquid formula diet required to maintain a 10% reduced weight. During leptin administration, energy expenditure, skeletal muscle work efficiency, sympathetic nervous system tone, and circulating concentrations of thyroxine and triiodothyronine returned to pre-weight-loss levels. These responses suggest that the weight-reduced state may be regarded as a condition of relative leptin insufficiency. Prevention of weight regain might be achievable by strategies relevant to reversing this leptin-insufficient state.
Endocrine, 2004
The aim of our study was to compare serum concentration of leptin and pituitary-thyroid axis hormones in obese/overweight women before and after two levels of energy deficit with those parameters in lean women on adequate energy intake. Additionally, we attempted to elucidate if the effect of weight reduction could be related to anthropometric and hormonal parameters before treatment. Anthropometric and hormonal parameters-serum leptin, TSH, T4, fT4, T3 and leptin to fat mass (Lep/fm), T3/T4, fT4/T4, T4/TSH, fT4/TSH-were compared in two groups of women (n = 18 each)-lean women (C: BMI 22.0 ± 1.2) and overweight/ obese (Ov/Ob: BMI 29.9 ± 3.3). Ov/Ob women were subjected to weight-reducing treatment consisting of energy intake equal to 80% of calculated total energy expenditure for the first 4 wk and to 50% for subsequent 4 wk. All baseline hormone concentrations, Lep/ fm, and fT4/T4 were higher in overweight/obese group. After 20% energy deficit decrease in BMI, percent body fat (fm%), leptin, T3, and TSH serum concentrations as well as in Lep/fm and T3/T4 was observed; T4/TSH increased, fT4, fT4/T4 and fT4/TSH did not change significantly. Increase in energy deficit from 20% to 50% resulted in normalization of Lep/fm, on the other hand, it provoked greater decline in thyroid hormone plasma concentration, which could hinder further mass reduction. Leptin and TSH levels were positively correlated after 50% energy deficit treatment. Changes in fm% were directly related to baseline T4/TSH, fT4/ TSH, and log TSH. In conclusion, TSH serum concentration and its ratio to T4 and fT4 before weight reduction could be a good predictor of successful weight loss.
Plasma concentrations of free triiodothyronine predict weight change in euthyroid persons
The American journal of clinical nutrition, 2007
Factors that influence energy metabolism and substrate oxidation, such as thyroid hormones (THs), may be important regulators of body weight. We investigated associations of THs cross-sectionally with obesity, energy expenditure, and substrate oxidation and prospectively with weight change. Euthyroid, nondiabetic, healthy, adult Pima Indians (n = 89; 47 M, 42 F) were studied. Percentage body fat (%BF) was measured by using dual-energy X-ray absorptiometry; sleeping metabolic rate (SMR), respiratory quotient, and substrate oxidation rates were measured in a respiratory chamber. Thyroid-stimulating hormone (TSH), free thyroxine (T(4)), free triiodothyronine (T(3)), and leptin concentrations were measured in fasting plasma samples. TSH, but neither free T(3) nor free T(4), was associated with %BF and leptin concentrations (r = 0.27 and 0.29, respectively; both: P <or= 0.01). In multiple regression analyses adjusted for age, sex, fat mass, and fat-free mass, free T(3) was a positive ...
Triiodothyronine(T3) neogenesis in lean and obese rats
Biochemical and Biophysical Research Communications, 1986
Pre-obese LA/N-cp rats consumed more food and gained weight more rapidly than their lean littermates, and measures of adipose tissue depots indicated that the excess weight was deposited principally as carcass fat. Serum T9 concentrations and resting metabolic rates were lower in corpulent than in lean animals, consistent with a greater efficiency of weight gain in those animals. In vitro measures of T9 neogenesis from T4 were lower in corpulent than in lean animals in liver, kidney, and skeletal muscle and greater in interscapular brown adipose tissue. The intracellular generation of T8 from T4 is a fundamental component of the normal adaptive response to alterations in diet and environment, and is an essential prerequisite for the expression of non-shivering thermogenesis. These results are consistent with a functional impairment in the activity of the enzyme T4-5'-deiodinase in peripheral tissues, and suggest that this impairment is contributory if not causative of obesity in this strain of rat.
Effect of tri-iodothyronine on leptin release and leptin mRNA accumulation in rat adipose tissue
The Biochemical journal, 1998
Leptin, the product of the obese gene, is produced by white adipocytes. The release of leptin, as well as leptin mRNA content, was enhanced in adipocytes isolated from hypothyroid rats. The administration of tri-iodothyronine (T3) 8 h before death inhibited leptin release by adipocytes incubated for 6 or 24 h. Direct addition of T3 to pieces of adipose tissue enhanced the loss of leptin mRNA seen over 24 h in the presence of dexamethasone plus the beta3-adrenergic agonist Cl 316,243. In contrast, if pieces of adipose tissue were incubated with dexamethasone plus insulin, enhanced the T3 accumulation of leptin mRNA. These results indicate that T3 enhances net adipocyte leptin mRNA accumulation in a condition that approximates the fed state (presence of insulin) but inhibits leptin mRNA accumulation in a condition that approximates the fasted state (absence of insulin).
Triiodothyronine(T3) neogenesis in lean and obese LAN-cp rats
Biochemical and Biophysical Research Communications, 1986
Pre-obese LA/N-cp rats consumed more food and gained weight more rapidly than their lean littermates, and measures of adipose tissue depots indicated that the excess weight was deposited principally as carcass fat. Serum T9 concentrations and resting metabolic rates were lower in corpulent than in lean animals, consistent with a greater efficiency of weight gain in those animals. In vitro measures of T9 neogenesis from T4 were lower in corpulent than in lean animals in liver, kidney, and skeletal muscle and greater in interscapular brown adipose tissue. The intracellular generation of T8 from T4 is a fundamental component of the normal adaptive response to alterations in diet and environment, and is an essential prerequisite for the expression of non-shivering thermogenesis. These results are consistent with a functional impairment in the activity of the enzyme T4-5'-deiodinase in peripheral tissues, and suggest that this impairment is contributory if not causative of obesity in this strain of rat.
Thyroid hormone metabolism in obesity
International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 2000
Serum thyroid hormone concentrations and their metabolic fate are within the normal range limits in obese subjects. Also serum TSH concentrations and its response to TRH are normal, suggesting that tissue availability of thyroid hormones is normally preserved in these subjects. In contrast, during caloric restriction serum T3 concentrations decrease as a consequence of its reduced production rate from peripheral deiodination of T4. Opposite, serum rT3 concentrations markedly increase as a result of its decreased metabolic clearance rate. During caloric overfeeding serum T3 concentration increase whereas serum rT3 concentrations decrease. In this condition the production rate of T3 increases. During caloric restriction and overfeeding serum T4 concentrations and its production and degradation are not modified.
Biochemical Journal, 1981
We have investigated the effects of thyroidectomy, hypophysectomy and 3,3′,5-tri-iodothyronine replacement on protein synthesis and degradation in skeletal muscle in vivo. Thyroidectomy resulted in a decrease in the rate of protein synthesis as a result of a loss of RNA. However, RNA activity, the rate of protein synthesis per unit of RNA, was not decreased. This was the case in both young growing rats and mature nongrowing rats. Tri-iodothyronine treatment of thyroidectomized rats increased protein synthesis by increasing RNA concentration without changes in RNA activity, and this occurred even when food intake was restricted to prevent any increase in growth. The rate of protein degradation was decreased by thyroidectomy and increased by tri-iodo-thyronine replacement in both animals fed ad libitum and food-restricted animals. Hypophysectomy decreased protein synthesis by decreasing both RNA concentration and activity. these changes were reversed by tri-iodothyronine treatment eve...