Why thyroxine increase metabolic rate

To assess the dietary intake, a three-day dietary record was used. Before each clinic visit, patients were asked to record the type and amount of each food consumed for 3 days two weekdays and one weekend day. Total energy and nutrient intake were calculated using the nutritional analysis program CAN-Pro version 5. To evaluate the quality of life, SF was surveyed before and after 52 weeks of treatment.

The score was converted into points. Height, weight, waist circumference, hip circumference, body composition, blood pressure, and heart rate were measured at each clinic visit. Body composition including lean mass, fat mass, and fat content was measured by bioelectrical impedance with the body composition analyzer InBody , Biospace, Seoul, Korea.

Respired gases oxygen and carbon dioxide were analyzed, and resting energy expenditure REE was calculated indirectly. The predicted REE was calculated as follows: [ 9 ]. Muscle strength was evaluated with an electronic handgrip dynamometer Lavisen, Namyangju, Korea because it is feasible, convenient, and inexpensive.

The handgrip strength was measured 3 times in each hand with at 1-minute intervals, and the average values were used for the analysis. After the study was completed, free triiodothyronine fT3 and total thyroxine TT4 were measured with the stored blood at 0, 12, 26, and 52 weeks after the treatment. To compare parameters before and after the treatment, the paired Wilcoxon test was performed.

The change in food intake and muscle strength over time was analyzed using a linear mixed model. All statistical analyses were performed with SPSS version All patients preferred the antithyroid drug treatment and were treated with methimazole. The average starting dose was Fifty-two weeks after the initial treatment, the dose was reduced to 6. The changes in the biochemical parameters are shown in Table 1. Twenty-six weeks after the treatment, all patients had achieved a normal thyroid function: the thyroid hormone decreased gradually from week 4 to week 26, and TSH increased at a later time from week 12 to week 26 Table 1.

After a week treatment of methimazole, the titer of anti-TSH receptor antibodies was decreased with marginal significance Systolic blood pressure decreased significantly while diastolic blood pressure remained unchanged Table 2. Heart rate also decreased significantly Table 2. Although a beta-blocker was used in 2 patients until week 26 of the treatment, the heart rate remained decreased at week 52 of the treatment.

Total cholesterol with both HDL and LDL cholesterols significantly increased after treatment, while triglyceride showed no change Table 1. At the time of diagnosis, the mean body weight and BMI were During the initial 8 weeks of treatment, the BMI significantly increased, reaching a peak at week 8, and then, it plateaued until week 26 Table 2.

At 52 weeks after the treatment, the BMI was slightly decreased but still higher than that at the baseline without any statistical significance. Although the hip circumference was slightly increased, the waist-to-hip ratio was not different after the treatment Table 2. Because a higher food intake with an increased appetite can be the major cause of weight gain, we first assessed the dietary energy intake using the three-day dietary record.

However, the total energy intake rapidly decreased from week 8 to week 12, and then, it was maintained up to week 52 ; Figure 1. There was no significant difference in the composition of macronutrients such as carbohydrates, proteins, and fats. The discordance of the weight gain and decreased food intake led us to hypothesize that weight changes are mainly due to the changes in energy metabolism. To verify this hypothesis, lean mass-corrected REE was investigated during the antithyroid treatment.

During the antithyroid treatment, the REE gradually decreased until week Taken together, the increased REE according to the thyrotoxicosis is near completely rescued after the week treatment following euthyroidism.

Furthermore, we investigated the association between REE and several parameters of thyroid homeostasis. The calculated peripheral deiodinase activity in untreated patients with hyperthyroidism was markedly increased by more than 2. To further explore the compositional changes of the whole body, bioelectrical impedance analysis was performed. The body is largely composed of three components: fat mass, lean mass, and bone mineral content.

As shown in Table 2 , both lean mass and fat-free mass gradually increased until 52 weeks after the treatment: 4. Interestingly, the maximum fat mass was observed at an earlier time week 12, while that of the lean mass was observed at a later time week 52 Figure 3 a.

Both DXA at baseline and week 52 were available for four patients, and the change in regional fat and lean mass was observed Figure 3 b. To assess whether the increased lean mass was accompanied by functional gain in muscle strength, the handgrip test was performed. Consistent with the lean mass changes, handgrip strength was significantly increased from 26 to 52 weeks after the treatment in both the dominant and nondominant hands ; Figure 4. There was no significant difference between the dominant and nondominant hands.

The present study showed 3 key findings. First, treatment-related acute weight gain during the initial 6-month treatment of hyperthyroidism is reversed during the next 6 months with the recovery of the normal thyroid function.

Second, the antithyroid treatment results in an increased body weight along with a decreased REE despite the decreased food intake. Third, the compositional analyses showed that fat mass increased during the initial 3 months and then reversed itself, while lean mass and muscle strength increased in the later 6 months suggesting body composition changes in a better direction.

The thyroid hormone is an important determinant of REE [ 1 ]. Finally, D3 is almost undetectable in the liver of healthy individuals, but robust re-activation of D3 has been found in regenerating liver tissue, in certain hepatic tumors and in sera and liver samples from critically ill humans, thus influencing the systemic thyroid status These results suggest that D3 plays a role in the tissue response to injury and in the imbalance of TH homeostasis commonly observed during critical illness.

However, the exact physiological role of TH in glucose homeostasis remains controversial 29 , Indeed, hyperthyroidism is associated with glucose intolerance consequent to decreased insulin secretion 31 , 32 and to stimulation of hepatic gluconeogenesis Probably, in hyperthyroid conditions, impaired insulin secretion is not sufficient to suppress high hepatic glucose production.

Accordingly, the prevalence of diabetes mellitus in hyperthyroid patients is approximately double that of non-affected subjects In contrast, systemic hypothyroidism is associated with reduced hepatic gluconeogenesis and enhanced insulin sensitivity, as demonstrated by the onset of a hypoglycemic state after an insulin injection In this context, the TH hormone-inactivating deiodinase D3 plays a fundamental role in lineage fate decisions and endocrine cell specification The pancreatic phenotype of the D3KO mice is proof that attenuation of TH-signaling via D3 activation is essential for normal development.

Peripheral TH signals are integrated within the hypothalamus and processed into coordinated responses to regulate energy balance. The center for regulation of food intake and of body weight is the melanocortin system, constituted by three neuronal populations: the pro-opiomelanocortin POMC -expressing neurons, the neuropeptide Y NPY and agouti-related peptide AgRP -co-expressing neurons and the melanocortin 4 receptor MC4R -expressing neurons 37 , The POMC neurons exert an anorexigenic function by activating MC4R neurons, which induce a reduction of food intake and increased energy expenditure.

All these neurons are sensitive to the TH signal that can either activate or inhibit melanocortin neurons, and thus, it is not surprising that local TH metabolism plays a critical role in appetite and feeding regulation. Changes in central T3 levels occur in various metabolic conditions 39 , for example elevated T3 levels have been found in the hypothalamus during fasting Fasting induces alterations in the thyroid state, namely, a reduction in pituitary D2 levels and liver D1 levels correlated with low peripheral T3 levels in the presence of increased hypothalamic D2 activity.

Therefore, under food deprivation, despite a reduction in peripheral TH levels, there is a localized increase in T3 within the hypothalamus, which in turn increases orexigenic signals and decreases TRH production. The hypothalamus probably maintains low TH levels to preserve energy stores, which would be dissipated in hyperthyroid condition. The fundamental role of deiodinases in the regulation of energy balance in brain has been demonstrated in mouse models of deiodinases depletion The enhanced TH levels alter the functioning of the hypothalamic circuitries, including the leptin-melanocortin system, thereby regulating energy balance and adiposity.

The hypothalamic D2-mediated T4 to T3 conversion is important for the photoperiodic response of the gonads 44 in which fine-tuned D2 and D3 expression tightly regulates LH stimulation TH influences skeletal muscle contraction, regeneration and metabolism During skeletal muscle development, D2 is up-regulated, particularly during the first postnatal days, and decreases at day 30, although its activity returns to high levels during differentiation of muscle stem cells 12 , 48 , In particular, during post-injury regeneration processes, D2 mRNA is up-regulated to enable correct myoblast differentiation D2 is a target of FOXO3, which is a protein involved in myocyte fusion and metabolism as well as in atrophy and autophagy Loss of D2 impairs stem cell differentiation and prevents up-regulation of myogenic transcription factor MyoD thereby increasing the proliferative potential of muscle stem cells.

D2-mediated TH in skeletal muscle influences also muscle fibers. D2-dependent T3 activation influences insulin response in skeletal muscle Indeed, D2KO mice are insulin-resistant, which demonstrates the relevance of D2 in glucose homeostasis.

In humans, a common polymorphism of the Dio2 gene, the Thr92Ala substitution in protein D2, which partially impairs enzymatic activity, has been correlated with insulin resistance and diabetes 53 , Furthermore, muscle fibers respond to cold through TH-related mechanisms, namely increased glucose uptake, activation of oxidative pathways and increased mitochondria biogenesis 55 , Interestingly, D2 is up-regulated in muscle after 4 h of cold exposure Coordinated D2-D3 expression is required to fine-tune intracellular TH availability during muscle stem cell differentiation, and in vivo , during muscle regeneration While D2 is essential for a correct T3 surge and the subsequent differentiation of muscle stem cells, D3 fosters muscle stem cell proliferation by lowering TH availability during the early phases of the myogenic program This dual regulation is so critical that D3-depletion in vivo causes massive apoptosis of proliferating satellite cells and drastically impairs a full regeneration process.

These studies highlight the pivotal role of the intracellular TH coordination by the deiodinases in muscle physiology. Brown adipose tissue is characterized by multilocular lipid droplets and numerous mitochondria, and governs heat production In fact, BAT is activated in response to a high fat diet or cold exposure in order to protect the organism from weight gain and hypothermia.

Thyroid hormone critically influences BAT activity The most obvious metabolic role of D2 is the regulation of energy expenditure in the BAT of small mammals, including human newborns.

During cold exposure, the sympathetic nervous system induces D2 expression in brown adipocytes, thereby promoting local T4-to-T3 conversion, and activation of the transcription of target genes involved in the thermogenic program D2 is thus considered a marker of BAT activity 1 , While D2 activity is important during differentiation, D3 is considered a mitogenic marker in brown pre-adipocytes.

Consequently, D2KO mice have reduced fatty acid oxidation and lipogenesis 4. The primary function of white adipose tissue WAT is to store energy in the form of single large lipid droplets, although it also secretes the leptin and adiponectin adipokines.

White adipocytes differ anatomically and physiologically from brown adipocytes. Interestingly, D1 expression and activity are increased in the subcutaneous and visceral WAT of obese subjects A high-fat diet stimulates D1 and leptin expression, while caloric restriction decreases D1 activity as well as leptin levels, and increases levels of the leptin mediator SCD Leptin overexpression increases D1 activity and down-regulates SCD-1 expression Similar to brown adipocytes, in white adipocytes, D2 plays an important role in lipogenesis and in the regulation of the expression of genes related to adipocyte differentiation, while D3 sustains the proliferation of white adipocytes Interestingly, thyroidectomized mice have an increased level of both D1 and D2 Moreover, D2 is expressed also in human pre-adipocytes although its role is unclear Monodeiodination is quantitatively the most important pathway of TH activation.

Within peripheral tissue, multiple pathways modulate TH availability. These pathways govern the action and regulation of deiodinase expression, the action of TH transporters, and the expression and crosstalk of TH receptors with multiple partners. This intricate network of TH modifiers increases the sensitivity and the speed of responses to changes induced in the internal and external environment by the thyroid signal.

The price to be paid for this is an intricate regulation of each component in time and space. Given the vast spectrum of metabolic body functions regulated by the TH signal, the deiodinases represent a powerful tool with which to modulate cellular metabolism in specific tissues without perturbing systemic levels of THs. Consequently, the development of drugs that target deiodinase action is the next challenge in this field.

Extensive work is still required to delineate the kinetics and regulation of the deiodinase enzymes in specific tissues to understand the full spectrum of their biological roles.

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The Node : the community site for and by developmental biologists. FocalPlane : the community site for microscopists and biologists alike. Sign In or Create an Account. Advanced Search. User Tools. Sign in. Skip Nav Destination Article Navigation. Close mobile search navigation Article navigation. Volume 2, Issue 6. Previous Article Next Article. Article contents. Materials and Methods. Article Navigation. Thyroid hormones correlate with resting metabolic rate, not daily energy expenditure, in two charadriiform seabirds Kyle H.

Elliott , Kyle H. This site. Google Scholar. Jorg Welcker , Jorg Welcker. Anthony J. Gaston , Anthony J. Scott A. Hatch , Scott A. Geological Survey, Alaska Science Center. Vince Palace , Vince Palace. James F. Hare , James F. John R. Speakman , John R. Gary Anderson W. Gary Anderson. Author and article information. Jorg Welcker. Vince Palace. Competing interests The authors have no competing interests to declare. Received: 13 Feb Accepted: 26 Feb Published by The Company of Biologists Ltd.

Biol Open 2 6 : — Article history Received:. Cite Icon Cite. Table 1. View Large. View large Download slide. Table 2. Correlation coefficients for relationships between thyroid hormones and either DEE or post-absorptive, unstressed RMR. Table 3. You may experience symptoms such as fatigue, sleepiness, muscle weakness, constipation , sensitivity to cold, cognitive problems, dry skin , a hoarse voice, lower appetite, joint pain, and menstrual changes, says Antonio Bianco, MD, PhD, a professor of medicine at the University of Chicago.

When people think of metabolism, though, they generally think of weight. People with a slower metabolism may have difficulty losing weight because they tend to burn fewer calories, which means that more get stored in the body as fat, according to Harvard Health.

A faster metabolism causes calories to be burned at a higher rate. How fast or slow your metabolism works is determined for the most part by your genes. But a number of other factors can play a role, including your age, your gender , your body size and composition, and your level of physical activity. Try these tips:. Take thyroid hormone. If you have hypothyroidism, which can be diagnosed with a blood test , your doctor will prescribe synthetic thyroid hormone.

Rev up with exercise.