Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.4.1.2 (acetyl-CoA carboxylase)
 2,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Akt is critical in insulin-induced metabolism of glucose and lipids. To investigate functions induced by hepatic Akt activation, a constitutively active Akt, NH(2)-terminally myristoylation signal-attached Akt (myr-Akt), was overexpressed in the liver by injecting its adenovirus into mice. Hepatic myr-Akt overexpression resulted in a markedly hypoglycemic, hypoinsulinemic, and hypertriglyceridemic phenotype with fatty liver and hepatomegaly. To elucidate the sterol regulatory element binding protein (SREBP)-1c contribution to these phenotypic features, myr-Akt adenovirus was injected into SREBP-1 knockout mice. myr-Akt overexpression induced hypoglycemia and hepatomegaly with triglyceride accumulation in SREBP-1 knockout mice to a degree similar to that in normal mice, whereas myr-Akt-induced hypertriglyceridemia in knockout mice was milder than that in normal mice. The myr-Akt-induced changes in glucokinase, phosphofructokinase, glucose-6-phosphatase, and PEPCK expressions were not affected by knocking out SREBP-1, whereas stearoyl-CoA desaturase 1 induction was completely inhibited in knockout mice. Constitutively active SREBP-1-overexpressing mice had fatty livers without hepatomegaly, hypoglycemia, or hypertriglyceridemia. Hepatic acetyl-CoA carboxylase, fatty acid synthase, stearoyl-CoA desaturase 1, and glucose-6-phosphate dehydrogenase expressions were significantly increased by overexpressing SREBP-1, whereas glucokinase, phospho-fructokinase, glucose-6-phosphatase, and PEPCK expressions were not or only slightly affected. Thus, SREBP-1 is not absolutely necessary for the hepatic Akt-mediated hypoglycemic effect. In contrast, myr-Akt-induced hypertriglyceridemia and hepatic triglyceride accumulation are mediated by both Akt-induced SREBP-1 expression and a mechanism involving fatty acid synthesis independent of SREBP-1.
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PMID:Hepatic Akt activation induces marked hypoglycemia, hepatomegaly, and hypertriglyceridemia with sterol regulatory element binding protein involvement. 1463 50

This paper describes the antitumoral activity of branched-chain fatty acid (BCFA) in human breast cancer cells with an emphasis on its effect on fatty acid biosynthesis. First, the relationship between chain-length and antitumoral activity was studied. The highest activity was observed with iso-16:0, and the activity decreased with increase or decrease of the chain-lengths from C16:0. Anteiso-BCFA, as well as iso-series, was cytotoxic to the breast cancer cells. Cytotoxicity of BCFA was comparable to that of conjugated linoleic acid known as antitumoral fatty acid. Incubation of breast cancer cells with BCFA (13-methyltetradecanoic acid) significantly reduced the [14C] acetate incorporation into free fatty acid and fatty acid esters, showing the inhibition of fatty acid biosynthesis by BCFA. Examination of substrate level effect found that BCFA slightly inhibited fatty acid synthetase and acetyl-CoA carboxylase, and significantly the glucose-6-phosphate dehydrogenase which was the main NADPH generating system in breast cancer cells. The present study thus suggests that BCFA synthetically lowers the fatty acid biosynthesis by reducing the precursors, in addition to its direct inhibitory effect on fatty acid synthetase.
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PMID:Effect of branched-chain fatty acids on fatty acid biosynthesis of human breast cancer cells. 1524 18

Fourteen Alpine goats at midlactation were fed a diet of hay and concentrate (55:45), without (control) or with formaldehyde-treated linseed (FLS) or oleic sunflower oil (OSO) at 11.2 or 3.5% of dry matter intake, respectively, in a 3 x 3 Latin Square design with three 3-wk periods. Milk yield was lower in goats fed FLS than control or OSO (2.13 vs. 2.32 kg/d). Milk fat content was higher with FLS or OSO than control (40.8 vs. 33.8 g/kg). Formaldehyde-treated linseed and OSO caused a significant decrease (23 and 18%, respectively) of C10 to C17 fatty acids secretion compared with control. The secretion of cis-9 C18:1 and cis-9, trans-11 C18:2 were increased 1.44- and 1.54-fold for FLS and 1.78- and 1.36-fold for OSO, compared with control. The C18:3 (n-3) secretion was increased 2.61-fold with FLS compared with control. Milk cis-9 C14:1/C14:0, cis-9 C16:1/C16:0, and cis-9 C18:1/C18:0 ratios decreased with the supplemented diets compared with control. Mammary stearoyl-CoA desaturase mRNA and activity were decreased by the lipid supplements, whereas no significant change was observed for acetyl-CoA carboxylase and fatty acid synthase. The activities of glucose-6-phosphate dehydrogenase, malic enzyme, and glycerol-3-phosphate dehydrogenase were not affected by the lipid supplements. Mammary lipoprotein lipase mRNA increased with OSO, whereas lipoprotein lipase activity tended to decrease with FLS compared with control. Milk lipoprotein lipase activity sharply decreased with lipid supplement (by 59 and 71%, for FLS and OSO, respectively). The changes in milk fatty acid profile due to FLS and OSO supplements were partly related to changes in the levels of mammary enzyme activities or mRNA.
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PMID:Mammary lipid metabolism and milk fatty acid secretion in alpine goats fed vegetable lipids. 1577 17

We have previously shown that in vivo lipogenesis is markedly reduced in liver, carcass, and in 4 different depots of adipose tissue of rats adapted to a high protein, carbohydrate-free (HP) diet. In the present work, we investigate the activity of enzymes involved in lipogenesis in the epididymal adipose tissue (EPI) of rats adapted to an HP diet before and 12 h after a balanced diet was introduced. Rats fed an HP diet for 15 days showed a 60% reduction of EPI fatty acid synthesis in vivo that was accompanied by 45%-55% decreases in the activities of pyruvate dehydrogenase complex, ATP-citrate lyase, acetyl-CoA carboxylase, glucose-6-phosphate dehydrogenase, and malic enzyme. Reversion to a balanced diet for 12 h resulted in a normalization of in vivo EPI lipogenesis, and in a restoration of acetyl-CoA carboxylase activity to levels that did not differ significantly from control values. The activities of ATP-citrate lyase and pyruvate dehydrogenase complex increased to about 75%-86% of control values, but the activities of glucose-6-phosphate dehydrogenase and malic enzyme remained unchanged 12 h after diet reversion. The data indicate that in rats, the adjustment of adipose tissue lipogenic activity is an important component of the metabolic adaptation to different nutritional conditions.
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PMID:Adaptation to a high protein, carbohydrate-free diet induces a marked reduction of fatty acid synthesis and lipogenic enzymes in rat adipose tissue that is rapidly reverted by a balanced diet. 1604 47

Intramuscular fat content is generally associated with improved sensory quality and better acceptability of fresh pork. However, conclusive evidence is still lacking for the biological mechanisms underlying i.m. fat content variability in pigs. The current study aimed to determine whether variations in i.m. fat content of longissimus muscle are related to i.m. adipocyte cellularity, lipid metabolism, or contractile properties of the whole muscle. To this end, crossbred (Large White x Duroc) pigs exhibiting either a high (2.82 +/- 0.38%, HF) or a low (1.15 +/- 0.14%, LF) lipid content in LM biopsies at 70 kg of BW were further studied at 107 +/- 7 kg of BW. Animals grew at the same rate, but HF pigs at slaughter presented fatter carcasses than LF pigs (P = 0.04). The differences in i.m. fat content between the 2 groups were mostly explained by variation in i.m. adipocyte number (+127% in HF compared with LF groups, P = 0.005). Less difference (+13% in HF compared with LF groups, P = 0.057) was noted in adipocyte diameter, and no significant variation was detected in whole-muscle lipogenic enzyme activities (acetyl-CoA carboxylase, P = 0.9; malic enzyme, P = 0.35; glucose-6-phosphate dehydrogenase, P = 0.75), mRNA levels of sterol-regulatory element binding protein-1 (P = 0.6), or diacylglycerol acyltransferase 1 (P = 0.6). Adipocyte fatty acid binding protein (FABP)-4 protein content in whole LM was 2-fold greater in HF pigs than in LF pigs (P = 0.05), and positive correlation coefficients were found between the FABP-4 protein level and adipocyte number (R2 = 0.47, P = 0.02) and lipid content (R2 = 0.58, P = 0.004). Conversely, there was no difference between groups relative to FABP-3 mRNA (P = 0.46) or protein (P = 0.56) levels, oxidative enzymatic activities (citrate synthase, P = 0.9; beta-hydroxyacyl-CoA dehydrogenase, P = 0.7), mitochondrial (P = 0.5) and peroxisomal (P = 0.12) oxidation rates of oleate, mRNA levels of genes involved in fatty acid oxidation (carnitine-palmitoyl-transferase 1, P = 0.98; peroxisome proliferator-activated receptor delta, P = 0.73) or energy expenditure (uncoupling protein 2, P = 0.92; uncoupling protein 3, P = 0.84), or myosin heavy-chain mRNA proportions (P > 0.49). The current study suggests that FABP-4 protein content may be a valuable marker of lipid accretion in LM and that i.m. fat content and myofiber type composition can be manipulated independently.
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PMID:Number of intramuscular adipocytes and fatty acid binding protein-4 content are significant indicators of intramuscular fat level in crossbred Large White x Duroc pigs. 1661 10

The aim of the present work was to investigate the effects of trans-10,cis-12 conjugated linoleic acid (CLA) on the activity and expression of lipogenic enzymes and lipoprotein lipase (LPL), as well as on the expression of transcriptional factors controlling these enzymes, in adipose tissue from hamsters, and to evaluate the involvement of these changes in the body fat-reducing effect of this CLA isomer. Thirty male hamsters were divided into three groups and fed atherogenic diets supplemented with 0 (linoleic group), 5 or 10 g trans-10,cis-12 CLA/kg diet, for 6 weeks. Body and adipose tissue weights, food intake and serum insulin were measured. Total and heparin-releasable LPL and lipogenic enzyme activities (acetyl-CoA carboxylase (ACC); fatty acid synthase (FAS); glucose-6-phosphate dehydrogenase (G6PDH); and malic enzyme (ME)) were assessed. ACC, FAS, LPL, sterol regulatory element-binding proteins (SREBP-1a), SREBP-1c and PPARgamma mRNA levels were also determined by real-time PCR. CLA did not modify food intake, body weight and serum insulin level. CLA feeding reduced adipose tissue weight, LPL activity and expression, and increased lipogenic enzyme activities, despite a significant reduction in ACC and FAS mRNA levels. The expression of the three transcriptional factors analysed (SREBP-1a, SREBP-1c and PPARgamma) was also reduced. These results appear to provide a framework for partially understanding the reduction in body fat induced by CLA. Inhibition of LPL activity seems to be an important mechanism underlying body fat reduction in hamsters. Further research is needed to better characterize the effects of CLA on lipogenesis and the role of these effects in CLA action.
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PMID:trans-10,cis-12 Conjugated linoleic acid inhibits lipoprotein lipase but increases the activity of lipogenic enzymes in adipose tissue from hamsters fed an atherogenic diet. 1676 33

The objectives of the current studies were to determine the roles of key enzymes in central carbon metabolism in the context of increased production of antibiotics in Streptomyces coelicolor. Genes for glucose-6-phosphate dehydrogenase and phosphoglucomutase (Pgm) were deleted and those for the acetyl coenzyme A carboxylase (ACCase) were overexpressed. Under the conditions tested, glucose-6-phosphate dehydrogenase encoded by zwf2 plays a more important role than that encoded by zwf1 in determining the carbon flux to actinorhodin (Act), while the function of Pgm encoded by SCO7443 is not clearly understood. The pgm-deleted mutant unexpectedly produced abundant glycogen but was impaired in Act production, the exact reverse of what had been anticipated. Overexpression of the ACCase resulted in more rapid utilization of glucose and sharply increased the efficiency of its conversion to Act. From the current experiments, it is concluded that carbon storage metabolism plays a significant role in precursor supply for Act production and that manipulation of central carbohydrate metabolism can lead to an increased production of Act in S. coelicolor.
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PMID:Engineering of primary carbohydrate metabolism for increased production of actinorhodin in Streptomyces coelicolor. 1695 Aug 96

Maternal diabetes is associated with an increased risk of miscarriages and congenital anomalies. Preovulatory oocytes in murine models also experience maturational delay and greater granulosa cell apoptosis. The objective of this study was to examine whether maternal diabetes influences preovulatory oocyte metabolism and impacts meiotic maturation. Streptozotocin-induced diabetic B6SJLF1 mice were superovulated, and oocytes were collected at 0, 2, and 6 h after human chorionic gonadotropin (hCG) injection. Individual oocyte concentrations of ATP, 5'-AMP, glycogen, and fructose-1,6-phosphate (FBP) and enzyme activities of glucose-6-phosphate dehydrogenase (G6PDH), adenylate kinase, hydroxyacyl-CoA dehydrogenase (Hadh2), and glutamic pyruvate transaminase (Gpt2) were measured. Protein levels of phosphorylated AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) were also measured. ATP levels were significantly lower in oocytes from diabetic mice, and the percent change in the AMP-to-ATP ratio was significantly higher in these oocytes. In contrast, activities of Hadh2 and Gpt2, two enzymes activated by AMPK, were significantly less in these oocytes. Additionally, glycogen and FBP levels, both endogenous inhibitors of AMPK, were elevated. Phosphorylated ACC, a downstream target of AMPK, and phosphorylated AMPK were both decreased in diabetic oocytes, thus confirming decreased AMPK activity. Finally, addition of the activator AICAR to the in vitro maturation assay restored AMPK activity and corrected the maturation defect experienced by the oocytes from diabetic mice. In conclusion, maternal diabetes adversely alters cellular metabolism leading to abnormal AMPK activity in murine oocytes. Increasing AMPK activity in these oocytes during the preovulatory phase reverses the metabolic changes and corrects delays in meiotic maturation.
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PMID:Maternal diabetes adversely affects AMP-activated protein kinase activity and cellular metabolism in murine oocytes. 1885 49

Plant oils in the diet are known to alter milk fat composition owing to changes in the supply of fatty acid precursors and/or activity of lipogenic enzymes in the mammary gland. Thirteen mid-lactating Alpine goats were used in a 3 x 3 Latin square design with 28-d periods to evaluate possible mechanisms regulating milk fat synthesis and fatty acid composition on grass hay-based diets containing none (H) or 55 g/kg diet dry matter of sunflower-seed oil (HSO) or linseed oil (HLO). Inclusion of oils in the diet had no effect on milk yield but enhanced (P<0.05) milk fat secretion. Compared with the control, HLO and HSO decreased (P<0.05) C10-C16 secretion and increased (P<0.05) C18 output in milk, responses that were accompanied by reductions in milk fat cis-9 14:1/14:0, cis-9 18:1/18:0 and cis-9, trans-11 18:2/cis-9 18:1 concentration ratios. Plant oil supplements decreased (P<0.05) mammary stearoyl-CoA desaturase (SCD) activity but had no effect on SCD mRNA. Treatments had no effect on glucose-6-phosphate dehydrogenase, malic enzyme and glycerol-3-phosphate dehydrogenase activity, or mRNA abundance and/or activity of lipoprotein lipase, acetyl-CoA carboxylase and fatty acid synthase in mammary, hepatic or adipose tissue. The results provided little support for milk fatty acid secretion responses to HLO and HSO being mediated via changes in mammary, hepatic or adipose mRNA abundance or in the activity of key lipogenic enzymes. In conclusion, plant oils in the diet enhance milk fat synthesis, alter milk fatty acid composition and specifically inhibit mammary SCD activity in the goat. Furthermore, the results suggest that the regulation of mammary lipogenesis in response to plant oils appears related to factors other than altered mammary gene expression or potential lipogenic enzyme activity.
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PMID:Effect of sunflower-seed oil or linseed oil on milk fatty acid secretion and lipogenic gene expression in goats fed hay-based diets. 1928 29

Lipid in the diet is known to enhance milk fat secretion and alter milk fatty acid composition in lactating goats. In the current experiment, the contribution of peripheral tissue and mammary gland lipid metabolism to changes in milk fat composition from plant oils was examined. Fourteen Alpine goats in midlactation were used in a 3 x 3 Latin square design with 28-d experimental periods. Treatments comprised maize silage-based diets containing no additional oil (M), sunflower-seed oil (MSO; 6.1% of diet DM), or linseed oil (MLO; 6.2% of diet DM). Compared with the control, milk yield was greater in goats fed MSO (3.37 and 3.62 kg/d, respectively), whereas MLO enhanced milk fat content (+3.9 g/kg), resulting in a 14% increase in milk fat secretion. Both MSO and MLO increased milk lactose secretion by 12 and 8%, respectively, compared with M. Relative to the control, plant oils decreased C10 to C16 secretion (32 and 24%, respectively, for MSO and MLO) and enhanced C18 output in milk (ca. 110%). Diets MSO and MLO increased cis-9 18:1 secretion in milk by 25 and 31%, respectively, compared with M. The outputs of trans-11 18:1 and cis-9, trans-11 18:2 in milk were increased 8.34- and 6.02-fold for MSO and 5.58- and 3.71-fold for MLO compared with M, and MSO increased trans-10 18:1 and trans-10, cis-12 18:2 secretion. Plant oils decreased milk fat cis-9 14:1/14:0; cis-9 16:1/16:0; cis-9 18:1/18:0; and cis-9, trans-11 18:2/trans-11 18:1 concentration ratios but had no effect on mammary stearoyl-CoA desaturase mRNA or activity. Furthermore, changes in milk fatty acid secretion were not associated with alterations in mammary acetyl-CoA carboxylase mRNA and activity, abundance of mRNA encoding for lipoprotein lipase and fatty acid synthase, or malic enzyme and glycerol-3-phosphate dehydrogenase activity in mammary tissue. Mammary lipoprotein lipase activity was increased with MSO relative to MLO. Treatments had no effect on glucose-6-phosphate dehydrogenase, malic enzyme, glycerol-3-phosphate dehydrogenase activity, or mRNA abundance and/or activity of lipoprotein lipase, acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase in liver or adipose tissue. In conclusion, inclusion of sunflower-seed oil and linseed oil in maize silage-based diets alters milk fatty acid secretion in goats via mechanisms independent of changes in mammary, hepatic, or adipose tissue lipogenic gene expression. Furthermore, data provided indications that the regulation of mammary lipogenic responses to plant oils on starch-rich diets differs between the caprine and bovine.
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PMID:Effect of sunflower-seed oil and linseed oil on tissue lipid metabolism, gene expression, and milk fatty acid secretion in Alpine goats fed maize silage-based diets. 1992 11


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