The Regulation of Lipogenesis by Thyroid Hormone and Its Contribution to Thermogenesis*

Abstract

We have used the tritiated water method to quantitate the effects of thyroid hormone on lipogenesis in the rat and then determined the contribution of this process to thyroid hormone-induced thermogenesis. After thyroid hormone administration to hypothyroid animals, fatty acid synthesis rose after a lag time of 12-16 h and reached a plateau after 4-5 days. This is consistent with the kinetics of an increase in oxygen consumption measured by others in similar animals. A diurnal variation was maintained in all thyroid states, with the peak value in the middle of the dark period being 3-fold higher than the nadir. Fatty acid synthesis in the livers of hyperthyroid animals was 3- to 4-fold higher than that in euthyroid rats, which, in turn, was 3- to 5-fold higher than the rate observed in hypothyroid rats. Slightly smaller but similar fold increases were measured in epididymal fat. A stimulation of fatty acid synthesis by thyroid hormone was also measured in the rest of the carcass, with hyperthyroid rates being twice those in hypothyroid animals. The contribution of the liver was much greater in hyperthyroid rats (34% of total fatty acid synthesis) than in hypothyroid animals (5%). The energy costs of this synthesis were calculated and compared to published values for total oxygen consumption in different thyroid states. Thus, 6-10% of the total increment in oxygen consumption between hyperthyroid and hypothyroid animals could be attributed to lipogenesis, depending on which published figures were used. About 3% of this increment was due to the liver alone.

Functional relationship of thyroid hormone-induced lipogenesis, lipolysis, and thermogenesis in the rat.

“…The effect of thyroid hormone on S 14 gene expression is apparent within 10-20 min after triiodothyronine (T3)1 administration (5,6) and that on malic enzyme within 1-2 h (7). In contrast, a detectable increase in fatty acid synthesis does not occur until some 12-16 h later (8), presumably because of tle comparatively long t4 of accumulation of the enzyme proteins.…”

“…The rate of lipogenesis in whole animals was determined by the method ofStansbie et al (21) as previously applied in our laboratory (8). 3 mCi oftritiated water were injected per rat intraperitoneally at 0800 h. Animals were killed after 30 min by exsanguination from the aorta under light ether anesthesia and a uniform homogenate of the total carcass prepared.…”

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

“…There is an approximately fourfold acceleration in the rate of energy expenditure during the transition from hypothyroidism to thyrotoxicosis in rats (596,597). VO 2 is reduced to *50% once systemic hypothyroidism is achieved (597).…”

Hepatic regulation of fatty acid synthase by insulin and T3: evidence for T3genomic and nongenomic actions

“…Insulin and triiodothyronine (T 3 ) are involved in mediating the effects of diet on lipogenesis in vivo (34). Hepatic lipogenesis is increased in hyperthyroid states or in response to T 3 injection (10,15,19,24,25,28,62,71,76,83) as well as in hyperinsulinemic subjects (80). In vivo, these two hormones are also involved in the long-term regulation of lipogenic enzymes activities such as fatty acid synthase (37).…”

“…LIPOGENESIS CONVERTS DIETARY CARBOHYDRATES to fatty acids primarily in liver (28). Insulin and triiodothyronine (T 3 ) are involved in mediating the effects of diet on lipogenesis in vivo (34).…”