Interactions between insulin and thyroid hormone in the control of lipogenesis

Abstract

1. The effects of intragastric glucose feeding and L-tri-iodothyronine (T3) administration on rates of hepatic and brown-fat lipogenesis in vivo were examined in fed and 48 h-starved rats. 2. T3 treatment increased hepatic lipogenesis in the fed but not the starved animals. Brown-fat lipogenesis was unaffected or slightly decreased by T3 treatment of fed or starved rats. 3. Intragastric glucose feeding increased hepatic lipogenesis in control or T3-treated fed rats, but did not increase hepatic lipogenesis in starved control rats. Glucose feeding increased hepatic lipogenesis if the starved rats were treated with T3. Glucose feeding increased rates of brown-fat lipogenesis in all experimental groups. The effects of glucose feeding on liver and brown-fat lipogenesis were mimicked by insulin injection. 4. The increase in hepatic lipogenesis in T3-treated 48 h-starved rats after intragastric glucose feeding was prevented by short-term insulin deficiency, but not by (-)-hydroxycitrate, an inhibitor of ATP citrate lyase. The increase in lipogenesis in brown adipose tissue in response to glucose feeding was inhibited by both short-term insulin deficiency and (-)-hydroxycitrate. 5. The results tend to preclude pyruvate kinase and acetyl-CoA carboxylase as the sites of interaction of insulin and T3 in the regulation of hepatic lipogenesis in 48 h-starved rats. Other potential sites of interaction are discussed.

Effects of Triiodothyronine Administration on the Disposal of Oral [1-14C]-Triolein, Lipoprotein Lipase Activity and Lipogenesis in the Rat during Lactation and on Removal of the Litter

“…Recent work from this laboratory [40,41] has implicated insulin in the regulation of mammary-gland LPL, and therefore the combination of lower plasma insulin and prolactin after treatment of lactating rats with T3 may be responsible for the observed decrease in LPL (Table 1). In confirmation of previous studies [35,42,43], plasma insulin increased 3-fold on removal of the litter for 24 h, but it was not significantly decreased by T3 treatment. This finding suggests that the action of T3 to decrease adipose-tissue LPL activity (Table 2) does not involve changes in plasma insulin.…”

“…Hyperthyroidism has been associated with an increase in rat heart LPL activity [19,21,22], whereas in the skeletal muscle the enzyme activity is decreased [22]. In the present study there were no changes in the heart or soleus LPL activity 24 h after T3 administration in the lactating or litter-removed rats (Table 3). The increased lipid uptake by the skeletal muscle of T3-treated rats (Table 3) could be related to alterations in the blood flow after T3 treatment and/or the more effective capture of NEFA released from chylomicrons or very-low-density lipoproteins.…”

“…The low transfer of dietary [14C]lipid through the mammary gland was paralleled by a decrease (58 %) in LPL activity in this tissue in the; 3-treated rats (Table 1). Pup growth rate, maternal body weight and food intake were not affected after 24 h of T3 administration (results not shown).…”

“…It is generally agreed that thyroid hormone stimulates hepatic lipogenesis in the non-lactating rat [23][24][25]. In white adipose tissue the effect of T3 is uncertain; it has been reported that thyroid hormone treatment decreases [25,46] or increases [23] the synthesis of fatty acids in this tissue.…”

“…Studies with non-pregnant non-lactating rats have shown that excess thyroid hormones inhibit LPL activity in adipose tissue [17][18][19], and have variable effects on activity in heart and skeletal muscle [20][21][22]. In contrast, hyperthyroidism increases hepatic lipogenesis [23][24][25] …”