Lipogenic Enzymes of Rat Liver and Adipose Tissue. Dietary Variations and Effect of Polychlorinated Biphenyls

1994 ◽  
Vol 49 (9-10) ◽  
pp. 665-678 ◽  
Author(s):  
Meinrad Boll ◽  
Lutz W. D. Weber ◽  
Andreas Stampfl ◽  
Burkhard Messner

Abstract The lipogenic enzymes fatty acid synthase (FAS; EC 2.3.1.85), citrate cleavage enzyme (CCE; EC 4.1.3.8), malic enzyme (ME; EC 1.1.1.40), glucose-6-phosphate dehydrogenase (G6PDH; EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (PGDH; EC 1.1.1.44) were investigated in liver and in brown adipose tissue (BAT) of Wistar rats under various dietary conditions and in the presence of 15 to 250 ppm (approximately 0.045-0.75 μmol/kg chow) polychlorinated biphenyls (PCBs).In response to refeeding starved animals, enzyme activities in both tissues increased to above normal levels and thereafter exhibited pronounced oscillations of their activities. The extent of increase depended on the carbohydrate and fat content of the diet. The lipogenic enzymes could be grouped in two categories according to their sensitivity to dietary carbohydrate: FAS and CCE responded faster to smaller changes in dietary composition, while ME, G6PDH and PGDH required larger changes and more time to respond.Diet-induced alterations of enzyme activities were of the same order of magnitude in liver and BAT. They were age-dependent, being more pronounced in young animals. Independent of the type of dietary manipulations, activities changed in a coordinate fashion, i.e., the changes of the activities of all 5 enzymes occurred at similar ratios to each other with an identical time course.Feeding PCB-containing diets resulted in a considerable increase of the activities of the lipogenic enzymes in liver, which was significantly greater with ME, G 6PD H and PGDH. The effect was dose-dependent but transient. In liver the response to PCB feeding was iden­tical in male and female animals, whereas in BAT lipogenic activities increased in females, but decreased in males.Refeeding starved animals with a PCB-containing diet led to an additional stimulation of the normal refeeding-induced increase of the enzyme activities in liver and BAT. This PCB-induced increase was 2-fold for FAS and CCE, but up to 15-fold for the other enzymes. All PCB-induced effects were significantly less pronounced in old than in young animals.In primary hepatocytes activities increased in hormone-free medium in the presence of PCBs. While activity was induced in insuline-and triiodothyronine-containing medium, this increase was significantly greater with PCBs present.

1969 ◽  
Vol 114 (1) ◽  
pp. 83-88 ◽  
Author(s):  
Jerry W. Young ◽  
Sylvia L. Thorp ◽  
Helen Z. De Lumen

The activities of phosphoenolpyruvate carboxykinase, ‘malic enzyme’, citrate-cleavage enzyme and glucose 6-phosphate dehydrogenase were assayed in homogenates of rumen mucosa, liver and adipose tissue of cattle. Rumen mucosa cytoplasm contained activities of ‘malic enzyme’ approximately sevenfold those of phosphoenolpyruvate carboxykinase, suggesting that the conversion of propionate into lactate by rumen mucosa involves ‘malic enzyme’. Neither starvation for 8 days nor feeding with a concentrate diet for at least 3 months before slaughter produced enzyme patterns in the tissues different from those in cattle given only hay, except that the all-concentrate diet caused increased activities of glucose 6-phosphate dehydrogenase and ‘malic enzyme’ in adipose tissues. Rumen mucosa, liver and adipose tissue contained phosphoenolpyruvate carboxykinase activity. ‘Malic enzyme’ was absent in liver. Citrate-cleavage enzyme activity was present in liver and adipose tissue but was quite low in rumen mucosa. Liver contained much less glucose 6-phosphate dehydrogenase activity than rumen mucosa or adipose tissue.


1996 ◽  
Vol 51 (11-12) ◽  
pp. 859-869 ◽  
Author(s):  
Meinrad Boll ◽  
Lutz W. D Weber ◽  
Andreas Stampfl

Abstract Nutrition-induced effects on the activity of enzymes of lipogenesis, fatty acid synthase (FAS; EC 2.3.1.85). ATP citrate lyase (ACL; EC 4.1.3.8), malic enzyme (ME; EC 1.1.1.40), glucose-6-phosphate dehydrogenase (G6PDH; EC 1.1.1.49) and 6-phosphogluconate dehy­ drogenase (PGDH; EC 1.1.1.44) were investigated in liver and interscapular brown adipose tissue (BAT) of rats. The lipogenic enzymes could be grouped into two categories according to their response to dietary manipulations; FAS and ACL. both key enzymes of lipogenesis, responded fast and strongly to dietary manipulations. ME, G6PDH and PDGH, enzymes which also contribute to metabolic pathways other than lipogenesis, responded in a more sustained and less pronounced fashion. Feed deprivation caused the specific activities of lipogenic enzymes to decline several-fold. Refeeding of previously fasted (up to 3 days) animals increased the activities dramatically (10-to 25-fold) to far above pre-fasting levels (“overshoot”). Repetition of the fasting/refeeding regimen increasingly impaired the ability of both tissues to synthesize overshooting enzyme activities in the subsequent refeeding period. The fasting-induced decline of the activities was prevented when sugars were provided to the animals via drinking water. The sugars displayed different effectivities; sucrose= glucose> fructose> maltose » lactose. Sugars as the sole nutrient after fasting were also able to induce overshooting enzyme activities. Again, activities of FAS and ACL responded in a more pronounced fashion than the other three enzymes. Transition from feeding one diet to feeding a new diet of different composition led to adaptation of the lipogenic enzyme activities to levels characteristic for the new diet. Replacing a low-carbohydrate with a high-carbohydrate diet proceeded with major alterations of enzyme activities. This process of attaining a new level took up to 20 days and involved pronounced oscillations of the specific activities. In contrast, when a high-carbohydrate diet was replaced with another diet, particular one high in fat, transition to new enzyme activities was completed within 2 -3 days and proceeded without oscillations. All dietary manipulations caused more pronounced responses in young (35d-old) than in adult (180d-old) animals.


1993 ◽  
Vol 265 (2) ◽  
pp. E252-E258 ◽  
Author(s):  
W. J. Yeh ◽  
P. Leahy ◽  
H. C. Freake

Thyroid hormone regulates lipogenesis differently in rat liver and brown adipose tissue (BAT). In the hypothyroid state, lipogenesis is suppressed in liver but enhanced in BAT. Here we investigated the mechanisms underlying increased lipogenesis in hypothyroid BAT. Housing the animals at 28 degrees C decreased lipogenesis in hypothyroid BAT to euthyroid levels. Denervation resulted in a 90% reduction in lipogenesis in hypothyroid BAT such that levels were lower than in euthyroid tissue. Thyroid hormone treatment of hypothyroid rats stimulated fatty acid synthesis in denervated BAT, as in liver, but decreased it in intact BAT. Steady-state levels of mRNA encoding acetyl-CoA carboxylase, fatty-acid synthase, and spor 14 were measured in similar animals by Northern analysis. The expression of these mRNAs mirrored the lipogenic data, showing that both thyroid hormone and the sympathetic nervous system work at a pretranslational level in this tissue. These data suggest that the increased BAT lipogenesis found with hypothyroidism is mediated by the sympathetic nervous system to counter the reduction in metabolic rate in these animals.


1987 ◽  
Vol 65 (11) ◽  
pp. 955-959 ◽  
Author(s):  
Hasmukh V. Patel ◽  
Karl B. Freeman ◽  
Michel Desautels

The time course of changes in the level of uncoupling protein mRNA when cold-acclimated mice were returned to a thermoneutral environment (33 °C) was examined using a cDNA probe. Upon deacclimation, there was a marked loss of uncoupling protein mRNA within 24 h, which precedes the loss of uncoupling protein from mitochondria. This loss of uncoupling protein mRNA was selective, since there was no change in the relative proportion of cytochrome c oxidase subunit IV mRNA or poly(A)+ RNA in total RNA. The results suggest that the decrease in the mitochondrial content of uncoupling protein during deacclimation is likely the result of turnover of existing protein, with very little replacement due to a lower level of its mRNA.


1993 ◽  
Vol 291 (1) ◽  
pp. 109-113 ◽  
Author(s):  
R Burcelin ◽  
J Kande ◽  
D Ricquier ◽  
J Girard

We have studied the time course and relative effects of hypoinsulinaemia and hyperglycaemia on concentrations of uncoupling protein (UCP) and glucose transporter (GLUT4) and their mRNAs in brown adipose tissue (BAT) during the early phase of diabetes induced by streptozotocin. Two days after intravenous injection of streptozotocin, plasma insulin concentration was at its lowest and glycaemia was higher than 22 mmol/l. After 3 days, a 60% decrease in BAT UCP mRNA concentration and a 36% decrease in UCP was observed. Concomitantly, there was an 80% decrease in GLUT4 mRNA and a 44% decrease in GLUT4 levels. When hyperglycaemia was prevented by infusing phlorizin into diabetic rats, BAT UCP mRNA and protein levels were further decreased (respectively 90% and 60% lower than in control rats). In contrast, the marked decreases in GLUT4 mRNA and protein concentrations in BAT were similar in hyperglycaemic and normoglycaemic diabetic rats. Infusion of physiological amounts of insulin restored normoglycaemia in diabetic rats, and BAT UCP and GLUT4 mRNA and protein concentrations were maintained at the level of control rats. When insulin infusion was stopped, a 75% decrease in BAT UCP mRNA level and a 75% decrease in GLUT4 mRNA level were observed after 24 h, but UCP and GLUT4 concentrations did not decrease. This study shows that insulin plays an important role in the regulation of UCP and GLUT4 mRNA and protein concentrations in BAT. Hyperglycaemia partially prevents the rapid decrease in concentration of UCP and its mRNA observed in insulinopenic diabetes whereas it did not affect the decrease in GLUT4 mRNA and protein concentration. It is suggested that UCP is produced by a glucose-dependent gene.


1993 ◽  
Vol 264 (5) ◽  
pp. R1017-R1023 ◽  
Author(s):  
G. Kortner ◽  
K. Schildhauer ◽  
O. Petrova ◽  
I. Schmidt

To determine developmental changes of brown adipose tissue (BAT) thermogenic activity at defined circadian and thermal states, we evaluated the time course of cold-induced increases of in vitro guanosine 5'-diphosphate (GDP) binding in parallel with whole body metabolism (oxygen consumption, VO2) and core temperature (Tc) in 1- to 11-day-old rat pups. During the maximum phase of the juvenile diurnal cycle, Tc of littermates was recorded continuously and VO2 alternately until 2 min before animals were killed for removal of interscapular BAT. GDP binding after 1.5 h at thermoneutrality and its increase during physiologically comparable cold loads were significantly lower in 1-day-old pups than in 5- and 11-day-old pups. Cold defense was activated more rapidly in the older pups, but GDP binding in even the 1-day-old pups was significantly increased during the second 10-min period of cold exposure. We conclude that rapid changes in thermogenic activity, in connection with the known developmental changes in the dependence of the suckling rat's metabolic cold defense on maternal and sibling contact and circadian phase, will distort longitudinal studies of any fast-changing BAT parameter when the conditions immediately before tissue removal are not thoroughly controlled.


1993 ◽  
Vol 264 (6) ◽  
pp. E874-E881 ◽  
Author(s):  
S. D. Carvalho ◽  
N. Negrao ◽  
A. C. Bianco

The activities of malic enzyme (ME) and glucose-6-phosphate dehydrogenase (G-6-PDH), two NADPH-generating lipogenic enzymes, were measured in brown adipose tissue (BAT) of rats undergoing various neurohormonal manipulations. Methimazole-induced hypothyroidism doubled the activity of these two enzymes but, surprisingly, triiodothyronine (T3) given to hypothyroid rats caused a time- and dose-dependent stimulation of up to three- to fourfold. Unilateral BAT denervation modestly reduced the activity of these enzymes (approximately 30%) and failed to prevent the stimulation induced by hypothyroidism, whereas growth hormone (GH) successfully blocked this effect of hypothyroidism. Insulin stimulated both enzymes regardless of the thyroid status but failed to abolish the inhibitory effect of GH. In intact rats, cold exposure caused a time-dependent increase in the activity of both ME and G-6-PDH, which reached 5.2- and 3-fold, respectively, after 96 h. This cold-induced stimulation was not observed in hypothyroid rats, but it was restored by physiological doses of thyroxine (800 ng.100 g body wt-1.24 h-1). Replacement with T3 (300 ng.100 g body wt-1.24 h-1), in contrast, did not have this effect. In hypothyroid rats with hemidenervation of BAT, norepinephrine (NE) modestly increased ME and G-6-PDH activities in the denervated side, with little or no effect in the intact side. Receptor-saturating doses of T3 (50 micrograms.100 g body wt-1.day-1 over 48 h) stimulated two- and threefold both enzymes in both sides, reducing or obliterating the effect of denervation. The data suggest a complex neurohormonal regulation of the activity of ME and G-6-PDH in BAT.(ABSTRACT TRUNCATED AT 250 WORDS)


1999 ◽  
Vol 276 (5) ◽  
pp. E896-E906 ◽  
Author(s):  
Gerhard Heldmaier ◽  
Martin Klingenspor ◽  
Martin Werneyer ◽  
Brian J. Lampi ◽  
Stephen P. J. Brooks ◽  
...  

Djungarian hamsters ( Phodopus sungorus) acclimated to a short photoperiod (8:16-h light-dark cycle) display spontaneous daily torpor with ad libitum food availability. The time course of body temperature (Tb), metabolic rate, respiratory quotient (RQ), and substrate and enzyme changes was measured during entrance into torpor and in deep torpor. RQ, blood glucose, and serum lipids are high during the first hours of torpor but then gradually decline, suggesting that glucose is the primary fuel during the first hours of torpor, with a gradual change to lipid utilization. No major changes in enzyme activities were observed during torpor except for inactivation of the pyruvate dehydrogenase (PDH) complex in liver, brown adipose tissue, and heart muscle. PDH inactivation closely correlates with the reduction of total metabolic rate, whereas in brain, kidney, diaphragm, and skeletal muscle, PDH activity was maintained at the initial level. These findings suggest inhibition of carbohydrate oxidation in heart, brown adipose tissue, and liver during entrance into daily torpor.


2018 ◽  
Author(s):  
Adilson Guilherme ◽  
David J Pedersen ◽  
Felipe Henriques ◽  
Alexander H. Bedard ◽  
Elizabeth Henchey ◽  
...  

ABSTRACTWhite adipose tissue (WAT) secretes factors to communicate with other metabolic organs to maintain energy homeostasis. We previously reported that perturbation of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) causes expansion of sympathetic neurons within white adipose tissue (WAT) and the appearance of “beige” adipocytes. Here we report evidence that white adipocyte DNL activity is also coupled to neuronal regulation and thermogenesis in brown adipose tissue (BAT). Induced deletion of FASN in all adipocytes in mature mice (iAdFASNKO) enhanced sympathetic innervation and neuronal activity as well as UCP1 expression in both WAT and BAT. In contrast, selective ablation of FASN in brown adipocytes of mice (iUCP1FASNKO) failed to modulate sympathetic innervation and the thermogenic program in BAT. Surprisingly, DNL in brown adipocytes was also dispensable in maintaining euthermia when UCP1FASNKO mice were cold-exposed. These results indicate that DNL in white adipocytes influences long distance signaling to BAT, which can modify BAT sympathetic innervation and expression of genes involved in thermogenesis.


Sign in / Sign up

Export Citation Format

Share Document