Effects of glucocorticoid hormones on lipid-synthetic enzymes from different adipose tissue regions and from liver

1983 ◽  
Vol 61 (12) ◽  
pp. 1245-1250 ◽  
Author(s):  
David C. W. Lau ◽  
Daniel A. K. Roncari

The regional diversity of adipose tissue is dramatically accentuated in states of glucocorticoid excess, in which certain fat depots expand, while others contract. We have studied the molecular basis of this redistribution by determining the activity of fatty acid synthetase and enzymes catalyzing di- and tri-acylglycerol synthesis, in subcellular fractions from four adipose depots of rats injected with dexamethasone and from interscapular and epididymal adipocyte precursors after addition of either dexamethasone or corticosterone to confluent monolayers in secondary culture. Subcellular fractions from cervical and interscapular adipose tissue, as well as from cultured interscapular precursors, revealed a general increase in specific enzyme activity. The opposite trend was observed for retroperitoneal and epididymal fat tissue, as well as cultured epididymal precursors. Fatty acid synthetase and cytosolic phosphatidate phosphohydrolase appeared to be most responsive. The findings in culture indicate that the regional effects of glucocorticoids are partly independent of other circulating or neural factors. Injections of dexamethasone led to significantly enhanced specific activity of all the lipid-synthetic enzymes assayed in subcellular fractions from liver. Differences in hormonal influences between liver and certain fat tissue regions represent tissue specificity. In addition, the diverse effects of glucocorticoids on various adipose tissue depots indicate regional or "intratissue" specificity.

1980 ◽  
Vol 186 (3) ◽  
pp. 937-944 ◽  
Author(s):  
P A Sinnett-Smith ◽  
R G Vernon ◽  
R J Mayer

1. The specific activities of fatty acid synthetase, acetyl-CoA carboxylase and pyruvate dehydrogenase were measured in rat adipose-tissue extracts in pregnancy and lactation. Fatty acid synthetase specific activity correlates very closely with the rate of fatty acid synthesis, the enzyme specific activity decreasing after mid-pregnancy in a manner very similar to the rate of fatty acid synthesis. Acetyl-CoA carboxylase specific activity also decreases dramatically after mid-pregnancy. Initial pyruvate dehydrogenase specific activity shows a decrease between 2 days pre partum and 2 days post partum, but total enzyme activity shows no significant change in the same period. 2. Immunotitrations of fatty acid synthetase and pyruvate dehydrogenase activities were carried out; the titrations showed that the change in the fatty acid synthetase activity is due to a change in the enzyme amount; the amount of pyruvate dyhydrogenase does not change. Therefore the decrease in fatty acid biosynthesis in subcutaneous and parametrial adipose tissue in late pregnancy and early lactation is associated with a decrease in the amount of at least one of the enzymes involved in fatty acid biosynthesis. The correlation of these events with known hormonal changes is discussed.


1983 ◽  
Vol 214 (2) ◽  
pp. 443-449 ◽  
Author(s):  
P Grimaldi ◽  
C Forest ◽  
P Poli ◽  
R Negrel ◽  
G Ailhaud

ob17 cells convert into adipose-like cells when maintained in the presence of physiological concentrations of insulin and tri-iodothyronine. After this conversion, insulin removal from differentiated ob17 cells gives within 24-48 h a large decrease in fatty acid synthetase, glycerol 3-phosphate dehydrogenase and acid:CoA ligase activities, as well as in the rate of fatty acid synthesis determined by [14C]acetate incorporation into lipids. All parameters are restored by insulin addition to initial values within 24-48 h. Dose-response curves of insulin on the restoration of glycerol 3-phosphate dehydrogenase activity and of fatty acid synthesis give half-maximally effective concentrations close to 1 nM, in agreement with the affinity for insulin of the insulin receptors previously characterized in these cells. Immunotitration experiments indicate that the changes in the specific activity of fatty acid synthetase are due to parallel changes in the cellular enzyme content. Therefore the ob17 cell line should be a useful model to study the long-term effects of insulin on the modulation of lipid synthesis in adipose cells.


2007 ◽  
Vol 292 (3) ◽  
pp. E952-E963 ◽  
Author(s):  
Michael J. Jurczak ◽  
Arpad M. Danos ◽  
Victoria R. Rehrmann ◽  
Margaret B. Allison ◽  
Cynthia C. Greenberg ◽  
...  

Adipocytes express the rate-limiting enzymes required for glycogen metabolism and increase glycogen synthesis in response to insulin. However, the physiological function of adipocytic glycogen in vivo is unclear, due in part to the low absolute levels and the apparent biophysical constraints of adipocyte morphology on glycogen accumulation. To further study the regulation of glycogen metabolism in adipose tissue, transgenic mice were generated that overexpressed the protein phosphatase-1 (PP1) glycogen-targeting subunit (PTG) driven by the adipocyte fatty acid binding protein (aP2) promoter. Exogenous PTG was detected in gonadal, perirenal, and brown fat depots, but it was not detected in any other tissue examined. PTG overexpression resulted in a modest redistribution of PP1 to glycogen particles, corresponding to a threefold increase in the glycogen synthase activity ratio. Glycogen synthase protein levels were also increased twofold, resulting in a combined greater than sixfold enhancement of basal glycogen synthase specific activity. Adipocytic glycogen levels were increased 200- to 400-fold in transgenic animals, and this increase was maintained to 1 yr of age. In contrast, lipid metabolism in transgenic adipose tissue was not significantly altered, as assessed by lipogenic rates, weight gain on normal or high-fat diets, or circulating free fatty acid levels after a fast. However, circulating and adipocytic leptin levels were doubled in transgenic animals, whereas adiponectin expression was unchanged. Cumulatively, these data indicate that murine adipocytes are capable of storing far higher levels of glycogen than previously reported. Furthermore, these results were obtained by overexpression of an endogenous adipocytic protein, suggesting that mechanisms may exist in vivo to maintain adipocytic glycogen storage at a physiological set point.


1984 ◽  
Vol 246 (2) ◽  
pp. E123-E128 ◽  
Author(s):  
A. Shepherd ◽  
M. P. Cleary

Dehydroepiandrosterone (DHEA) is a known noncompetitive inhibitor of glucose-6-phosphate dehydrogenase (G6PD). In the present investigation, the effects of chronic DHEA treatment on G6PD and several other enzymes involved in lipid metabolism were examined in lean and obese Zucker rats. Significant decreases in body weight were found in DHEA-treated rats in comparison with nontreated rats. In lean rats, DHEA treatment did not decrease either liver or adipose tissue G6PD and fatty acid synthetase activity, but malic enzyme activity was increased. In obese rats, decreased liver and adipose tissue G6PD and fatty acid synthetase activities were found. Malic enzyme activity in liver of obese DHEA rats was increased but not in adipose tissue. Adipose tissue lipoprotein lipase activity was decreased in both lean and obese DHEA rats. Serum insulin in obese DHEA rats was also decreased compared with control obese rats. These results indicate that the inhibition of G6PD may not be the mechanism of action of the antiobesity effect of DHEA. However, the metabolic effects of DHEA seen in obese rats may contribute to its antiobesity action.


1979 ◽  
Vol 182 (2) ◽  
pp. 509-514 ◽  
Author(s):  
P M Ahmad ◽  
T R Russell ◽  
F Ahmad

3T3-L fibroblasts differentiate into adipose cells when maintained in a non-growing state. The specific activity of fatty acid synthetase of differentiated cells was 25–30-fold higher than that present in 3T3-L fibroblasts or in 3T3-C2 cells that possess an extremely low incidence of differentiation to adipocytes. The results of immunochemical analysis indicate that the increased specific activity of fatty acid synthetase in the differentiated cells is due to an increase in the cellular content of this enzyme. The rate of conversion of adipose cells was accelerated by brief exposure of confluent non-growing cultures of 3T3-L cells to 3-isobutyl-1-methylxanthine. This was accompanied by an increase in the specificity activity of fatty acid synthetase, which was also shown to be due to an increase in the cellular content of this enzyme. The continuous presence of 3-isobutyl-1-methylxanthine in the culture medium was not required to elicit the morphological and biochemical changes in 3T3-L cells that occurred many days after the removal of the inducer but earlier than the onset of spontanous differentiation.


1988 ◽  
Vol 251 (2) ◽  
pp. 547-551 ◽  
Author(s):  
J S Wilson ◽  
M A Korsten ◽  
L P Donnelly ◽  
P W Colley ◽  
J B Somer ◽  
...  

Administration of ethanol as part of a nutritionally adequate liquid diet to female Wistar rats was found to depress markedly incorporation of labelled glucose into adipose-tissue acylglycerol fatty acids. Similar results with labelled pyruvate and acetate suggested inhibition of the fatty-acid-synthesis pathway at, or distal to, the acetyl-CoA carboxylase step. Activities of acetyl-CoA carboxylase and fatty acid synthetase were markedly lower in ethanol-fed animals. The activity of another lipogenic enzyme, phosphatidate phosphohydrolase, was not affected by chronic ethanol feeding. These findings suggest that chronic ethanol administration has marked effects on adipose-tissue lipogenesis.


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