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)

The effects of a peroxisome proliferator activated receptor gamma (PPARgamma) agonist on hepatic stearoyl-CoA desaturase (SCD) in insulin-resistant and obese Zucker fa/fa rats were studied. The administration of pioglitazone, a PPARgamma agonist, to Zucker obese rats greatly improved their insulin sensitivity. The treatment of Zucker obese rats with pioglitazone did not affect the index of fatty acid desaturation of either serum or liver. Hepatic SCD activity and the mRNA level of SCD1 were not changed by treatment of the rats with pioglitazone. The activity of palmitoly-CoA chain elongase, which is involved in the biosynthesis of oleic acid in concert with SCD, was not significantly altered when Zucker obese rats received pioglitazone. Although neither the activity nor mRNA expression of acyl-CoA oxidase was changed by treatment of Zucker obese rats with pioglitazone, the mRNA expressions of both sterol regulatory element-binding protein-1c and acetyl-CoA carboxylase sensitively responded to the challenge by pioglitazone. These results suggest that the insulin sensitivity of insulin-resistant and obese Zucker fa/fa rats is improved by pioglitazone independently of SCD activity.
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PMID:Effects of pioglitazone on stearoyl-CoA desaturase in obese Zucker fa/fa rats. 1753 29

AMPK (AMP-activated protein kinase) has been suggested to be a central player regulating FA (fatty acid) metabolism through its ability to regulate ACC (acetyl-CoA carboxylase) activity. Nevertheless, its involvement in insulin resistance- and TD2 (Type 2 diabetes)-associated dyslipidaemia remains enigmatic. In the present study, we employed the Psammomys obesus gerbil, a well-established model of insulin resistance and TD2, in order to appreciate the contribution of the AMPK/ACC pathway to the abnormal hepatic lipid synthesis and increased lipid accumulation in the liver. Our investigation provided evidence that the development of insulin resistance/diabetic state in P. obesus is accompanied by (i) body weight gain and hyperlipidaemia; (ii) elevations of hepatic ACC-Ser79 phosphorylation and ACC protein levels; (iii) a rise in the gene expression of cytosolic ACC1 concomitant with invariable mitochondrial ACC2; (iv) an increase in hepatic AMPKalpha-Thr172 phosphorylation and protein expression without any modification in the calculated ratio of phospho-AMPKalpha to total AMPKalpha; (v) a stimulation in ACC activity despite increased AMPKalpha phosphorylation and protein expression; and (vi) a trend of increase in mRNA levels of key lipogenic enzymes [SCD-1 (stearoyl-CoA desaturase-1), mGPAT (mitochondrial isoform of glycerol-3-phosphate acyltransferase) and FAS (FA synthase)] and transcription factors [SREBP-1 (sterol-regulatory-element-binding protein-1) and ChREBP (carbohydrate responsive element-binding protein)]. Altogether, our findings suggest that up-regulation of the AMPK pathway seems to be a natural response in order to reduce lipid metabolism abnormalities, thus supporting the role of AMPK as a promising target for the treatment of TD2-associated dyslipidaemia.
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PMID:Increased hepatic lipogenesis in insulin resistance and Type 2 diabetes is associated with AMPK signalling pathway up-regulation in Psammomys obesus. 1884 11

Twenty-eight Angus steers (289 kg) were finished on a high-concentrate diet (85% concentrate: 15% roughage; CONC), or endophyte-free tall fescue pastures with corn grain supplement (0.52% of BW; PC), corn oil plus soybean hull supplement (0.10% of BW corn oil plus 0.45% of BW soybean hulls; PO), or no supplement (pasture only; PA). Subcutaneous adipose tissues were processed for total cellular RNA extraction and fatty acid composition by GLC. Relative expression of genes involved in lipogenesis [fatty acid synthase (FASN), acetyl-CoA carboxylase, lipoprotein lipase, stearoyl-CoA desaturase (SCD)] and activators of transcription [(peroxisome proliferator-activated receptor-gamma), C/EBPalpha, sterol regulatory binding protein-1, signal transducer and activator of transcription-5, and Spot-14] was determined by real-time quantitative PCR. Housekeeping gene (glyceraldehyde 3-phosphate dehydrogenase and beta-actin) expression was used in analysis to normalize expression data. Total fatty acid content was greatest (P < 0.001) for CONC and least (P < 0.001) for PA. Supplementation of grazing cattle increased (P < 0.001) total fatty acid content compared with PA, but concentrations were less (P < 0.001) than for CONC. Myristic and palmitic acid contents were greater (P < 0.001) for CONC than for PO and PC, which were greater (P < 0.001) than for PA. Stearic acid content was greater (P < 0.01) for PO than for CONC, PC, and PA. Finishing on CONC increased (P < 0.001) total MUFA content by 68% compared with PA. Corn grain supplementation increased (P < 0.001) MUFA content compared with PA; in contrast, MUFA content did not differ (P > 0.05) between PO and PA. Corn oil supplementation increased (P < 0.001) trans-11 vaccenic acid content in subcutaneous fat by 1.2-, 1.7- and 5.6-fold relative to PA, PC, and CONC, respectively. Concentrations of the cis-9, trans-11 CLA isomer were 54, 58, and 208% greater (P < 0.01) for PO than for PA, PC, and CONC, respectively. Corn grain supplementation to grazing steers did not alter (P > 0.05) the cis-9, trans-11 CLA isomer compared with PA. Oil supplementation increased (P < 0.001) linoleic acid (C18:2) content by 56, 98 and 262% compared with CONC, PC, and PA, respectively. Relative mRNA expression of SCD was upregulated (P < 0.001) by 46-, 18- and 7-fold, respectively, for CONC, PC, and PO compared with PA. Relative FASN mRNA expression was also upregulated (P = 0.004) by 9- and 5-fold, respectively, for CONC and PC compared with PA. Grain feeding, either on CONC or supplemented on pasture, upregulated FASN and SCD mRNA to increase MUFA and de novo fatty acids in subcutaneous adipose tissue. Upregulation of SCD with grain feeding and reduced tissue CLA concentrations suggest that the decreased CLA concentrations were the result of limited substrate (trans-11 vaccenic acid) availability.
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PMID:Corn oil or corn grain supplementation to steers grazing endophyte-free tall fescue. II. Effects on subcutaneous fatty acid content and lipogenic gene expression. 1902 50

Compound K (CK) is a major intestinal metabolite of ginsenosides derived from ginseng radix. Although antidiabetic and antihyperlipidemic activities of CK have been investigated in recent years, action mechanism of CK remains poorly understood. Therefore, we examined whether CK affects the lipid metabolism in insulin-resistant HepG2 human hepatoma cells. In this study, a significant increase in AMP-activated protein kinase (AMPK) was observed when the cells were treated with CK. Activation of AMPK was also demonstrated by measuring the phosphorylation of acetyl-CoA carboxylase (ACC), a substrate of AMPK. CK attenuated gene expression of sterol regulatory element-binding protein 1c (SREBP1c) in time- and dose-dependent manners. Genes for fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1), well-known target molecules of SREBP1c, were also suppressed. In contrast, gene expressions of peroxisome proliferator-activated receptor alpha (PPAR-alpha) and CD36 were increased. These effects were reversed by treatment of compound C, an AMPK inhibitor. However, there were no differences in gene expressions of SREBP2, hydroxymethyl glutaryl CoA reductase (HMGR), and low-density-lipoprotein receptor (LDLR). Taken together, AMPK mediates CK induced suppression and activation of SREBP1c and PPAR-alpha, respectively, and these effects seem to be one of antidiabetic and/or antihyperlipidemic mechanisms of CK in insulin-resistant HepG2 human hepatoma cells.
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PMID:Compound K, intestinal metabolite of ginsenoside, attenuates hepatic lipid accumulation via AMPK activation in human hepatoma cells. 1918 50

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

An experiment was conducted with 12 lactating dairy ewes and 12 goats with the objective to determine whether, under the same dietary treatments, the differences in their fatty acid (FA) profile with emphasis on cis-9 trans-11 CLA milk fat content, are reflected in the transcript levels of genes involved in FA and cis-9, trans-11 CLA biosynthesis. The animals were fed with two diets (A, B) in different days of milk (DIM) due to the different milk yield, body weight etc, in order to have the same food intake and to avoid dietary effects. Diet A was fed to the animals on a group basis as it is traditionally used in practice, while diet B was chosen to avoid individual feed intake variation which is usually observed in group feeding. The results showed that there are significantly lower mRNA levels of acetyl-CoA carboxylase (ACC) in sheep mammary gland compared with those of goats, independently from the diet fed. The same trend was observed with the mRNA level of FA synthase (FAS), but the results were significant only for diet A. The mRNA level of lipoprotein lipase (LPL) in the mammary gland did not differ between sheep and goats fed with diet A. In addition, the concentration of cis-9 trans-11 CLA content was significantly higher in sheep milk fat compared with those of goats. This is in accordance with the significant higher levels on mRNA of stearoyl-CoA desaturase (SCD) which were observed in their mammary adipocytes of sheep compared with those of goats, independently of the fed diet (A or B). In conclusion, these findings demonstrate that the differences between sheep and goats, concerning cis-9, trans-11 CLA and FA milk fat content, under the same dietary treatments could be explained in part by the differences in mRNA of SCD and lipogenic genes in their mammary gland.
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PMID:Sheep and goats differences in CLA and fatty acids milk fat content in relation with mRNA stearoyl-CoA desaturase and lipogenic genes expression in their mammary gland. 1963 67

The objectives of this study were 1) to determine whether selection toward less subcutaneous fat thickness at constant intramuscular fat content in pigs is related to tissue-specific changes in the expression of lipogenic enzymes acetyl-CoA carboxylase (ACC), stearoyl-CoA desaturase (SCD), and Delta(6)-desaturase (Delta6d); and 2) to investigate tissue specific distribution of the porcine ACC, SCD, and Delta6d. The study was conducted on 20 purebred Duroc barrows. Ten animals were from a group selected for decreased subcutaneous fat thickness at constant intramuscular fat content (experimental group). The other 10 animals were from the unselected (control) group. Distribution of ACC, SCD, and Delta6d was investigated in semimembranosus muscle (SM), subcutaneous adipose tissue (SA), liver (L), kidney (K), heart (H), diaphragm (D), rectus capitis muscle (RCM), and abdominal fat (AF). The enzyme expression was studied in 10 animals in the case of SM and SA and in 4 animals in the case of other tissues. The following expression pattern was established for ACC: SM <or= H = K <or= D < RCM < L < AF = SA, whereas the expression patterns for SCD and Delta6d proteins were SM < H < RCM < D < L < K < AF = SA and RCM = SM = D < L <or= H < SA < K < AF, respectively. Expression of ACC and SCD proteins was less in subcutaneous adipose tissue of the experimental animals when compared with the control group (P < 0.001). However, no difference (P > 0.1) in ACC and SCD protein expression between the control and experimental groups was observed in SM. Expression of Delta6d protein did not differ between the control and experimental groups for SA (P = 0.47) or SM (P = 0.31). There was a positive relationship between muscle SCD protein expression and intramuscular fat content (r = 0.48, P < 0.05). Intramuscular fat content did not correlate with ACC or Delta6d protein expression (P = 0.23 and P = 0.80, respectively). We conclude that SCD might be an effective potential biomarker for intramuscular fat deposition.
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PMID:Acetyl-CoA carboxylase and stearoyl-CoA desaturase protein expression in subcutaneous adipose tissue is reduced in pigs selected for decreased backfat thickness at constant intramuscular fat content. 1968 59

Cancer cells activate the biosynthesis of saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) in order to sustain an increasing demand for phospholipids with appropriate acyl composition during cell replication. We have previously shown that a stable knockdown of stearoyl-CoA desaturase 1 (SCD1), the main Delta9-desaturase that converts SFA into MUFA, in cancer cells decreases the rate of lipogenesis, reduces proliferation and in vitro invasiveness, and dramatically impairs tumor formation and growth. Here we report that pharmacological inhibition of SCD1 with a novel small molecule in cancer cells promoted the activation of AMP-activated kinase (AMPK) and the subsequent reduction of acetylCoA carboxylase activity, with a concomitant inhibition of glucose-mediated lipogenesis. The pharmacological inhibition of AMPK further decreased proliferation of SCD1-depleted cells, whereas AMPK activation restored proliferation to control levels. Addition of supraphysiological concentrations of glucose or pyruvate, the end product of glycolysis, did not reverse the low proliferation rate of SCD1-ablated cancer cells. Our data suggest that cancer cells require active SCD1 to control the rate of glucose-mediated lipogenesis, and that when SCD1 activity is impaired cells downregulate SFA synthesis via AMPK-mediated inactivation of acetyl-CoA carboxylase, thus preventing the harmful effects of SFA accumulation.
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PMID:Inhibition of stearoylCoA desaturase-1 inactivates acetyl-CoA carboxylase and impairs proliferation in cancer cells: role of AMPK. 1971 Sep 15

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

Sauchinone, as an AMP-activated kinase (AMPK)-activating lignan in Saururus chinensis, has been shown to prevent iron-induced oxidative stress and liver injury. Sterol regulatory element binding protein-1c (SREBP-1c) plays a key role in hepatic steatosis, which promotes oxidative stress in obese subjects. Previously, we identified the role of AMPK in liver X receptor-alpha (LXRalpha)-mediated SREBP-1c-dependent lipogenesis. Because sauchinone as an antioxidant has the ability to activate AMPK, this study investigated its effects on SREBP-1c-dependent lipogenesis in hepatocytes and in high-fat diet (HFD)-induced hepatic steatosis and oxidative injury. Sauchinone prevented the ability of an LXRalpha agonist (T0901317) to activate SREBP-1c, repressing transcription of the fatty acid synthase, acetyl-CoA carboxylase, stearoyl-CoA desaturase-1, ATP-binding cassette transporter A1, and LXRalpha genes. Consistent with this, an HFD in mice caused fat accumulation in the liver with SREBP-1c induction, which was attenuated by sauchinone treatment. Also, sauchinone had the ability to inhibit oxidative stress as shown by decreases in thiobarbituric acid-reactive substance formation, nitrotyrosinylation, and 4-hydroxynonenal production. Moreover, it prevented not only the liver injury, but also the AMPK inhibition elicited by HFD feeding. These results demonstrate that sauchinone has the capability to inhibit LXRalpha-mediated SREBP-1c induction and SREBP-1c-dependent hepatic steatosis, thereby protecting hepatocytes from oxidative stress induced by fat accumulation.
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PMID:Inhibition of SREBP-1c-mediated hepatic steatosis and oxidative stress by sauchinone, an AMPK-activating lignan in Saururus chinensis. 2000 44


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