Correction: Effects of PKB/Akt inhibitors on insulin-stimulated lipogenesis and phosphorylation state of lipogenic enzymes in white adipose tissue

We investigated acute effects of two allosteric protein kinase B (PKB) inhibitors, MK-2206 and Akti-1/2, on insulin-stimulated lipogenesis in rat epididymal adipocytes incubated with fructose as carbohydrate substrate. In parallel, the phosphorylation state of lipogenic enzymes in adipocytes and incubated epididymal fat pads was monitored by immunoblotting. Preincubation of rat epididymal adipocytes with PKB inhibitors dose-dependently inhibited the following: insulin-stimulated lipogenesis, increased PKB Ser473 phosphorylation, increased PKB activity and decreased acetyl-CoA carboxylase (ACC) Ser79 phosphorylation. In contrast, the effect of insulin to decrease the phosphorylation of pyruvate dehydrogenase (PDH) at Ser293 and Ser300 was not abolished by PKB inhibition. Insulin treatment also induced ATP-citrate lyase (ACL) Ser454 phosphorylation, but this effect was less sensitive to PKB inhibitors than ACC dephosphorylation by insulin. In incubated rat epididymal fat pads, Akti-1/2 treatment reversed insulin-induced ACC dephosphorylation, while ACL phosphorylation by insulin was maintained. ACL and ACC purified from white adipose tissue were poor substrates for PKBα in vitro. However, effects of wortmannin and torin, along with Akti-1/2 and MK-2206, on recognized PKB target phosphorylation by insulin were similar to their effects on insulin-induced ACL phosphorylation, suggesting that PKB could be the physiological kinase for ACL phosphorylation by insulin. In incubated epididymal fat pads from wild-type versus ACC1/2 S79A/S212A knockin mice, effects of insulin to increase lipogenesis from radioactive fructose or from radioactive acetate were reduced but not abolished. Together, the results support a key role for PKB in mediating insulin-stimulated lipogenesis by decreasing ACC phosphorylation, but not by decreasing PDH phosphorylation.

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Upregulation of lipogenic enzymes genes expression in white adipose tissue of rats with chronic renal failure is associated with higher level of sterol regulatory element binding protein-1

Metabolism ◽

10.1016/j.metabol.2004.02.015 ◽

2004 ◽

Vol 53 (8) ◽

pp. 1060-1065 ◽

Cited By ~ 25

Author(s):

Justyna Korczynska ◽

Ewa Stelmanska ◽

Anna Nogalska ◽

Marek Szolkiewicz ◽

Elzbieta Goyke ◽

...

Keyword(s):

Renal Failure ◽

Adipose Tissue ◽

Chronic Renal Failure ◽

White Adipose Tissue ◽

Binding Protein ◽

Regulatory Element ◽

Lipogenic Enzymes ◽

Genes Expression ◽

Element Binding Protein ◽

Sterol Regulatory Element

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Increased gene expression of lipogenic enzymes and glucose transporter in white adipose tissue of suckling and weaned obese Zucker rats

Biochemical Journal ◽

10.1042/bj2790303 ◽

1991 ◽

Vol 279 (1) ◽

pp. 303-308 ◽

Cited By ~ 37

Author(s):

L Pénicaud ◽

P Ferré ◽

F Assimacopoulos-Jeannet ◽

D Perdereau ◽

A Leturque ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Glucose Transporter ◽

Zucker Rats ◽

Lipogenic Enzymes ◽

Glut 4 ◽

Obese Rats ◽

Before And After ◽

Plasma Insulin Levels ◽

Obese Zucker Rats

Previous experiments have shown that insulin-induced glucose utilization is increased in white adipose tissue of young obese Zucker rats. We have investigated the possible role of over-expression of the muscle/fat glucose transporter (Glut 4) and key lipogenic enzymes in this increased insulin-responsiveness. The amount or activity and the mRNA concentrations of Glut 4, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) were measured before and after weaning in white adipose tissue of obese and lean Zucker rats. Comparison of the levels of Glut 4 and lipogenic-enzyme expression in 15-day-old suckling and 30-day-old weaned rats on a high-carbohydrate diet shows a marked increase in the latter group. The increase was, in lean and obese rats respectively, 6- and 7-fold for the amount of Glut 4 and 2- and 3-fold for its mRNA concentrations, 40- and 100-fold for the activity of lipogenic enzymes (FAS and ACC) and 30- and 10-fold for their mRNA concentrations. Furthermore, all these parameters, except the amount of Glut 4, were 2-5-fold higher in obese rats, both before and after weaning. Changes at weaning were largely blunted when rats were weaned on to a high-fat diet, although the differences between lean and obese rats persisted, and even became significant for the amount of Glut 4. Whatever the experimental conditions, plasma insulin levels were significantly higher in obese than in lean rats. These results indicate the existence of an enhanced expression of Glut 4, FAS and ACC in white adipose tissue of young obese fa/fa rats which could be related to the increased plasma insulin levels.

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Effects of high-carbohydrate diets on lipogenesis in rat interscapular brown adipose tissue

Biochemical Journal ◽

10.1042/bj2060667 ◽

1982 ◽

Vol 206 (3) ◽

pp. 667-669 ◽

Cited By ~ 2

Author(s):

P. John Weaire ◽

Tazeen F. Kanagasabai

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

White Adipose Tissue ◽

White Bread ◽

Lipogenic Enzymes ◽

Adipose Tissues ◽

Interscapular Brown Adipose Tissue ◽

High Carbohydrate ◽

Brown Adipose

Cycloplasmic preparations from brown and white adipose tissues were assayed for three lipogenic enzymes throughout a programme of starvation followed by refeeding on either a normal or a white-bread diet. In the brown adipose tissue of rats fed on a white-bread diet the three enzymes were elevated to levels significantly higher than those in white adipose tissue.

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