Bg

FIGURE 10 Effects of thyroxine on oxygen consumption by various tissues of thyroidectomized rats. Note that in (A) the abscissa is in units of hours and in (B) the units are days. N, normal; Tx-0, thyroidectomized just prior to thyroxine. (Redrawn from Barker SB, Klitgaard HM. Metabolism of tissues excised from thyroxine-injected rats. Am J Physiol 1952;170:81.)

FIGURE 10 Effects of thyroxine on oxygen consumption by various tissues of thyroidectomized rats. Note that in (A) the abscissa is in units of hours and in (B) the units are days. N, normal; Tx-0, thyroidectomized just prior to thyroxine. (Redrawn from Barker SB, Klitgaard HM. Metabolism of tissues excised from thyroxine-injected rats. Am J Physiol 1952;170:81.)

that maintain a constant body temperature, consistent with the idea that calorigenic effects may be related to thermoregulation. Thyroidectomized animals have severely reduced ability to survive cold temperature. T3 contributes to both heat production and heat conservation.

Individuals exposed to a cold environment maintain constant body temperature by increasing heat production by at least two mechanisms: (1) shivering, which is a rapid increase in involuntary activity of skeletal muscle, and (2) the so-called nonshivering thermogenesis seen in cold-acclimated individuals. Details of the underlying mechanisms for each of these responses are still not understood. As we have seen, the metabolic effects of T3 have a long lag time and hence increased production of T3 cannot be of much use for making rapid adjustments to cold temperatures. The role of T3 in the shivering response is probably limited to maintenance of tissue sensitivity to sympathetic stimulation. In this context, the importance of T3 derives from actions that were established before exposure to cold temperature. Maintenance of sensitivity to sympathetic stimulation permits efficient mobilization of stored carbohydrate and fat needed to fuel the shivering response and to make circulatory adjustments for increased activity of skeletal muscle. It may be also recalled that the sympathetic nervous system regulates heat conservation by decreasing blood flow through the skin. Piloerection in animals increases the thickness of the insulating layer of fur. These responses are likely to be of importance in both acute and chronic responses to cold exposure.

Chronic nonshivering thermogenesis appears to require increased production of T3, which acts in concert with the sympathetic nervous system to increase heat production and conservation. Some data indicate that norepinephrine may increase permeability of brown fat and skeletal muscle cells to sodium. Increased activity of the sodium pump could account for increased oxygen consumption and heat production in the cold acclimatized individual. In muscles of cold-acclimated rats, activity of the sodium-potassium ATPase is increased in a manner that appears to depend on thyroid hormone. Some experimental results support a similar effect on calcium pumps.

Brown fat is an important source of heat in newborn humans and throughout life in small mammals. This form of adipose tissue is especially rich in mitochondria, which give it its unique brown color. Mitochondria in this tissue contain UCP 1, sometimes called thermogenin, which allows them to oxidize relatively large amounts of fatty acids and produce heat unfettered by limitations in availability of ADP. Although both T3 and the sympathetic neurotransmitter norepinephrine can each induce the synthesis of UCP-1, their cooperative interaction results in production of 3-4 times as much of this mitochondrial protein as the sum of their independent actions. In addition, T3 increases the efficacy of norepi-nephrine to release fatty acids from stored triglycerides and thus provides fuel for heat production. Brown adipose tissue increases synthesis of the type II deiodi-nase in response to sympathetic stimulation, and produces abundant T3 locally to meet its needs. Adult humans have little brown fat, but may increase heat production through similar effects of UCP-2 and UCP-3 in white fat and muscle, but supporting evidence for this possibility is not available.

In rodents and other experimental animals, exposure to cold temperatures is an important stimulus for increased TSH secretion from the pituitary and the resultant increase in T4 and T3 secretion from the thyroid gland. Cold exposure does not increase TSH secretion in humans except in the newborn. In humans and experimental animals, however, exposure to cold temperatures increases conversion of T4 to T3 probably as a result of increased sympathetic nervous activity, which leads to increased cyclic AMP production in various tissues. Recall that expression of the type II deiodinase is activated by cyclic AMP.

Carbohydrate Metabolism

T3 accelerates virtually all aspects of metabolism including carbohydrate utilization. It increases glucose absorption from the digestive tract, glycogenolysis and gluconeogenesis in hepatocytes, and glucose oxidation in liver, fat, and muscle cells. No single or unique reaction in any pathway of carbohydrate metabolism has been identified as the rate-determining target of T3 action. Rather, carbohydrate degradation appears to be driven by other factors, such as increased demand for ATP, the content of carbohydrate in the diet, or the nutritional state. Although T3 may induce synthesis of specific enzymes of carbohydrate and lipid metabolism, e.g., the malic enzyme, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase, it appears to behave principally as an amplifier or gain control working in conjunction with other signals (Fig. 11). In the example shown, induction of the malic enzyme in hepatocytes was dependent both on the concentration of glucose in the culture medium and on the concentration of T3. T3 had little effect on enzyme induction when there was no glucose but amplified the effectiveness of glucose as an inducer of gene expression. This experiment provides a good example of how T3 can amplify readout of genetic information.

glucose concentration (mg/dl)

FIGURE 11 Effects of glucose and T3 on the induction of malic enzyme (ME) in isolated hepatocyte cultures. Note that the amount of enzyme present in tissues was increased by growing cells in higher and higher concentrations of glucose. Open bars show effects of glucose in the presence of a low (10~10 M) concentration of T3. Solid bars indicate that the effects of glucose were exaggerated when cells were grown in a high concentration of T3 (10~8 M). (From Mariash GN, Oppenheimer JH. Thyroid hormone-carbohydrate interaction at the hepatic nuclear level. Fed Proc 1982;41:2674.)

glucose concentration (mg/dl)

FIGURE 11 Effects of glucose and T3 on the induction of malic enzyme (ME) in isolated hepatocyte cultures. Note that the amount of enzyme present in tissues was increased by growing cells in higher and higher concentrations of glucose. Open bars show effects of glucose in the presence of a low (10~10 M) concentration of T3. Solid bars indicate that the effects of glucose were exaggerated when cells were grown in a high concentration of T3 (10~8 M). (From Mariash GN, Oppenheimer JH. Thyroid hormone-carbohydrate interaction at the hepatic nuclear level. Fed Proc 1982;41:2674.)

Psychology Of Weight Loss And Management

Psychology Of Weight Loss And Management

Get All The Support And Guidance You Need To Be A Success At The Psychology Of Weight Loss And Management. This Book Is One Of The Most Valuable Resources In The World When It Comes To Exploring How Your Brain Plays A Role In Weight Loss And Management.

Get My Free Ebook


Post a comment