Synergism of thyroid hormone and high carbohydrate diet in the induction of lipogenic enzymes in the rat. Mechanisms and implications.

Abstract

A B S T R A C T We have investigated the relationship between the administration of triiodothyronine (T3) and a high carbohydrate (CHO) fat-free diet in the induction of lipogenic enzymes in two rat tissues, liver, and fat. Male thyroidectomized rats were treated with graded daily doses of T3 and either supplemented with a high CHO diet or left on a regular diet. Enzymes studied included malic enzyme (ME), fatty acid synthetase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. In the liver, all four lipogenic enzymes showed a synergistic response between T3 administration and high CHO feeding. In fat, ME also responded synergistically. The interaction was reflected in ani increased sensitivity to T3. The dose of T3 required to achieve 50% Y maximal response was reduced three-to seven-fold by the high CHO diet. This phenomenon could not be attributed to a dietary-induced alteration either in T3 metabolism or in number or affinity of the T3-nuclear receptors. Moreover, studies of the relative rate of synthesis of ME suggested a simultaneous time of onset in the induction of ME, within 2 h after the application of either T3 or CHO. Thus, it is unlikely that either stimulus is secondary to the other. Since parallel experiments from this laboratory (Towle, Mariash, and Oppenheimer. 1980. Changes in hepatic levels of messenger ribonucleic acid for malic enzylme during induction by thyroid hormone or diet. show that ME induction both by CHO and T3 is mediated by an increase in specific messenger RNA for ME, the interaction of T3 and the dietary factor occurs at a pretranslational level.Dr.

Opposing effects of glucagon and triiodothyronine on the hepatic levels of messenger ribonucleic acid S14 and the dependence of such effects on circadian factors.

“…Ofinterest is the equally rapid response ofthe mature mRNA to the administration of dietary carbohydrate and the synergistic interaction between this dietary stimulus and T3 in the induction of mRNA-S14 (4). Such an interaction is typical of the behavior of several lipogenic enzymes previously studied in our laboratory (5). Another aspect ofthe regulation ofhepatic mRNA-S14 is the threefold circadian variation in expression that has been demonstrated in the unmanipulated animal (1).…”

Direct Role of ChREBP·Mlx in Regulating Hepatic Glucose-responsive Genes

“…Hence, any effect of the dominant negative Mlx that interfered with insulin signaling and SREBP-1c action might lead indirectly to an inhibition of the glucose effect. Thyroid hormones have also been shown to function together with glucose in supporting the induction of many lipogenic enzyme genes (39,40,46). Therefore, we tested the effect of introducing dominant negative Mlx on insulin and thyroid hormone signaling pathways.…”

“…Carbohydrate and thyroid hormones often have a synergistic effect on the regulation of these genes (40). To exclude the possibility that the inhibition of lipogenic enzyme genes by dominant negative Mlx is mediated by blocking the thyroid hormone pathway, we examined the effect of dominant negative Mlx on a thyroid hormone-responsive mRNA.…”

Insulin-like growth factor I reduces thyroid hormone receptors in the rat liver. Evidence for a feed-back loop regulating the peripheral thyroid hormone action

“…Malic enzyme [EC 1·1.1·40; -malate-NADP + oxidoreductase (decarboxylating)] was assayed in the cytosolic fraction by the method of Hsu & Lardy (1969) and expressed as U/mg DNA. One unit (U) was defined as the amount of the enzyme needed to catalyse the reduction of 1 nmol NADP/min using an extinction coefficient for NADPH of E mmol/l 340 =6·3 (Mariash et al 1980). The DNA content was evaluated in the total cellular homogenate and in the purified nuclear fraction by the method of Burton (1956).…”