Regulation of lipogenesis in the liver

The synthesis of several lipogenic enzymes is stimulated in the liver by thyroid hormones. For instance the concentration of acetyl Co A carboxylase, fatty acid synthetase and malic enzyme is increased in vivo after T3 injection [66-69], 

Malic enzyme catalyses the NADP-dependent oxidative decarboxylation of malate to pyruvate and C02 with the production of NADP which is utilized for the synthesis of long chain saturated fatty acids from malonyl CoA. 

Upon thyroid hormone stimulation the activity of malic enzyme is stimulated over 20-fold and this stimulation is paralleled by an increase in the mRNA level [70-72], The rate of malic enzyme mRNA accumulation is stimulated by T3 both in the rat liver and the heart (11-16-fold in the liver, 3-4-fold in the heart) [73], Nuclear 

A diet high in carbohydrates also stimulates malic enzyme activity and synthesis in rodent and avian liver while starvation or low carbohydrates has the opposite effect [67,74]. Recent data demonstrated [75] that a high-carbohydrate diet increases the cytoplasmic malic enzyme mRNA at a post-transcriptional level probably by retarding its degradation. Such a control is liver specific since no response was observed in brain, heart, kidney and other non-hepatic tissues. The amplitude of the response to the high carbohydrate diet is increased several fold by T3. 

Goodridge and co-workers (see Ref. 76) have developed a system of chick embryo hepatocytes which, when cultured in defined medium, respond to T3, insulin and glucagon. Low concentrations of T3 (K50 4xl0 n M) increase by 15-fold the malic enzyme level and 7-fold the concentration of its mRNA [77]. Insulin alone had no effect both on the enzyme and the mRNA levels, whereas in combination with T3 it caused an 11-fold increase in malic enzyme mRNA levels. Glucagon almost completely abolished the stimulatory effect caused by insulin + T3. Experiments performed with puromycin showed that this inhibitor of protein translation blocks the accumulation of malic enzyme mRNA stimulated by T3 suggesting that most of the T3 effect on malic enzyme takes place at a post-transcriptional step. Glucagon had no effect on transcription but caused malic enzyme mRNA to decay 

---