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

Casein-based diets containing a low (LDI) or high (HDI) dose of soya protein concentrate enriched with isoflavones were fed to obese Zucker rats for 6 weeks. HDI feeding, but not LDI feeding, reduced the fatty liver and decreased the plasma levels of alanine transaminase and aspartate transaminase. This was accompanied by increased activities of mitochondrial and peroxisomal beta-oxidation, acetyl-CoA carboxylase, fatty acid synthase and glycerol-3-phosphate acyltransferase in liver and increased triacylglycerol level in plasma. The decreased fatty liver and the increased plasma triacylglycerol level appeared not to be caused by an increased secretion of VLDL, as HDI decreased the hepatic mRNA levels of apo B and arylacetamide deacetylase. However, the gene expression of VLDL receptor was markedly decreased in liver, but unchanged in epididymal white adipose tissue and skeletal muscle of rats fed HDI, indicating that the liver may be the key organ for the reduced clearance of triacylglycerol-rich lipoproteins from plasma after HDI feeding. The n-3/n-6, 20:4n-6/18:2n-6 and (20:5n-3+22:6n-3)/18:3n-3 ratios were increased in liver triacylglycerol by HDI. The phospholipids in liver of rats fed HDI contained a low level of 20:4n-6 and a high level of 20:5n-3, favouring the production of anti-inflammatory eicosanoids. When obese Zucker rats were fed soya protein, this also resulted in reduced fatty liver, possibly through reduced clearance of VLDL by the liver. We conclude that the isoflavone-enriched soya concentrate as well as soya protein may be promising dietary supplements for treatment of non-alcoholic fatty liver.
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PMID:Dietary soya protein concentrate enriched with isoflavones reduced fatty liver, increased hepatic fatty acid oxidation and decreased the hepatic mRNA level of VLDL receptor in obese Zucker rats. 1692 18

Berberine (BBR), an isoquinoline alkaloid, has a wide range of pharmacological effects, yet its exact mechanism is unknown. In order to understand the anti-adipogenic effect of BBR, we studied the change of expression of several adipogenic enzymes of 3T3-L1 cells by BBR treatment. First, we measured the change of leptin and glycerol in the medium of 3T3-L1 cells treated with 1 micrometer, 5 micrometer and 10 micrometer concentrations of BBR. We also measured the changes of adipogenic and lipolytic factors of 3T3-L1. In 3T3-L1 cells, both leptin and adipogenic factors (SREBP-1c, C/EBP-alpha, PPAR-gamma, fatty acid synthase, acetyl-CoA carboxylase, acyl-CoA synthase and lipoprotein lipase) were reduced by BBR treatment. Glycerol secretion was increased, whereas expression of lipolytic enzymes (hormone-sensitive lipase and perilipin) mRNA was slightly decreased. Next, we measured the change of inflammation markers of 3T3-L1 cells by BBR treatment. This resulted in the down-regulation of mRNA level of inflammation markers such as TNF-alpha, IL-6, C- reactive protein and haptoglobin. Taken together, our data shows that BBR has both anti-adipogenic and anti-inflammatory effects on 3T3-L1 adipocytes, and the anti-adipogenic effect seems to be due to the down-regulation of adipogenic enzymes and transcription factors.
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PMID:Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte. 1720 35

Genistein is one of the most abundant isoflavones in soy. The effects of genistein on cholesterol synthesis and fatty acid oxidation have been well documented, but the effect of genistein on fatty acid synthesis remains unclear. Thus, we investigated the effect of genistein on fatty acid synthase (FAS) expressions in HepG2 cells. In HepG2 cells treated with 10 micromol/L genistein, mRNA and protein expressions of FAS, as well as FAS activity, were significantly decreased. The promoter region of FAS contains binding sites for the transcription factor called sterol regulated element binding protein 1 (SREBP-1); SREBP-1 must be processed by site-1 (S1P) and site-2 proteases to be activated. We also investigated the effects of genistein on S1P, SREBP-1 expression, and subsequent SREBP-1 processing by S1P in HepG2 cells. Genistein reduced the expression of S1P and the processing of SREBP-1 but did not change the expression of SREBP-1 mRNA. SREBP-1 is also a transcription factor for lipogenic genes, such as stearoyl coenzyme-A desaturase1 (SCD1), glycerol-3-phosphate acyltransferase (GPAT), and acetyl-CoA carboxylase (ACC)1, and ACC2. Genistein also significantly inhibited the expression of these lipogenic genes. Thus, genistein treatment of HepG2 cells decreased the expression of lipogenic genes such as FAS, SCD1, GPAT, and ACC, which is, at least in part, mediated through the downregulation of S1P expression and subsequent SREBP-1 proteolytic cleavage.
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PMID:Genistein downregulates SREBP-1 regulated gene expression by inhibiting site-1 protease expression in HepG2 cells. 1744 69

The effects of fasting on hepatic lipid metabolism in mice fed a high-fat diet (HFD) are still unclear. After fasting, the degree of hepatic lipid accumulation differs between HFD-fed C57BL/6J (B6) and BALB/cA (BALB/c) mice. It is not clear whether this difference is due to sensitivity to fasting or HFD. The aim of this study is to elucidate this difference among strains. After nine weeks of HFD feeding, both B6 and BALB/c mice showed moderate hepatic steatosis. However, after a subsequent twenty-hour fast, the hepatic lipid accumulation was markedly decreased in B6 but not in BALB/c mice. Moreover, the mRNA expression of a transcription factor, Srebp1(regulates hepatic lipid metabolism), and its target genes-malic enzyme, acetyl-CoA carboxylase, fatty acid synthase(regulate fatty acid synthesis), and glycerol-3-phosphate acyltransferase(regulates triacylglycerol synthesis)-were more markedly reduced in B6 than BALB/c mice. In conclusion, fasting may modify hepatic lipid accumulation in HFD-fed B6 and BALB/c mice differently. The difference may be partly owing to a marked downregulation of the expression of some lipid-metabolism-related genes in B6 mice. These results suggest that fasting per se has a significant effect on hepatic lipid accumulation in mouse strains. SREBP1 might play a role in this fasting effect.
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PMID:The effect of fasting on hepatic lipid accumulation and transcriptional regulation of lipid metabolism differs between C57BL/6J and BALB/cA mice fed a high-fat diet. 1881 81

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

In this study, we investigated the lipolytic effects of eicosapentaenoic acid (EPA) in 3T3-L1 adipocytes. The differentiated 3T3-L1 adipocytes were treated in a serum-free medium with 300 muM of EPA for 3, 6, 12, and 24 h. In comparison with the control, intracellular lipid accumulation was significantly decreased by 24% at 24 h following the addition of EPA (P < 0.05). Under the same experimental conditions, there was an increase of glycerol and free fatty acids (FFAs). The mRNA level of carnitine palmitoyltransferase I-a, a component of the fatty-acid shuttle system involved in the mitochondrial oxidation of long-chain fatty acids, was also significantly elevated by EPA (P < 0.05). However, the expression of peroxisome proliferator-activated receptor-gamma and acetyl-CoA carboxylase (ACC), which are involved in adipogenesis, was significantly down-regulated by EPA (P < 0.05). These results suggest that EPA may modulate lipid metabolism by stimulation of lipolysis, which was associated with induction of lipolytic gene expression and suppression of adipogenic gene expression in 3T3-L1 adipocytes.
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PMID:Eicosapentaenoic acid increases lipolysis through up-regulation of the lipolytic gene expression and down-regulation of the adipogenic gene expression in 3T3-L1 adipocytes. 1885 Feb 26

The aim of this study was to evaluate the concentration of oleanolic acids (OA) in pomace, a winemaking byproduct, and its influence on the levels of plasma lipids in rats fed a high-fat diet and on hepatic gene expression using DNA microarray analysis in vivo. HPLC analyses of pomace ethanol extract (PEE) revealed a high amount of OA ranging from 4 to 11 g/100 g. Male Sprague-Dawley rats were fed a normal-fat diet (NF group), a high-fat diet with 21% lard (HF group), a high-fat diet with 0.05% OA (OA group, 50 mg/kg/day), or a high-fat diet with 0.45% PEE (PEE group, 450 mg/kg/day). Plasma triacylglycerol and phospholipid concentrations were significantly lower in the OA and PEE groups than in the HF group. The microarray analysis of hepatic mRNA revealed reduced expression levels of lipogenic genes including acetyl-CoA carboxylase and glycerol-3-phosphate acyltransferase, probably resulting from the suppression of transcription factor Srebf1 expression. Gene expression of gluconeogensis and inflammatory cytokines was also down-regulated in the OA and PEE groups, suggesting that administration of OA or PEE could ameliorate obesity-induced insulin resistance, as well as prevent hyperlipidemia.
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PMID:Effect of dietary wine pomace extract and oleanolic acid on plasma lipids in rats fed high-fat diet and its DNA microarray analysis. 1905 93

This study investigated the role of adenosine monophosphate-activated protein kinase (AMPK) in the regulation of lipolysis in visceral (VC) and subcutaneous (SC) rat adipocytes and the molecular mechanisms involved in this process. VC (epididymal and retroperitoneal) and SC (inguinal) adipocytes were isolated from male Wistar rats (160-180 g). Adipocytes were incubated either in the absence or in the presence of the AMPK agonist 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR, 0-500 micromol/l). AMPK and acetyl-CoA carboxylase (ACC) phosphorylation, basal and epinephrine-stimulated (100 nmol/l) glycerol release, and hormone-sensitive lipase (HSL) phosphorylation and activity were determined. AICAR-induced (500 micromol/l) AMPK activation inhibited basal glycerol release by approximately 42, 41, and 44% in epididymal, retroperitoneal, and inguinal adipocytes, respectively. Epinephrine-stimulated glycerol release was almost completely prevented by AICAR treatment in adipocytes from all fat depots. The AMPK inhibitor compound C (20 micromol/l) prevented AICAR-induced phosphorylation of AMPK and significantly increased basal (approximately 1.3-, 1.4-, and 1.7-fold) and epinephrine-stimulated (approximately 1.3-, 1.2-, 1.4-fold) glycerol release in epididymal, retroperitoneal, and inguinal adipocytes, respectively. AICAR increased phosphorylation of HSL(Ser565) and inhibited epinephrine-induced phosphorylation of HSL(Ser563) and HSL(Ser660). This was also accompanied by a 73% reduction in epinephrine-stimulated HSL activity. Compound C prevented the phosphorylation of HSL(Ser565) induced by AICAR and partially prevented the inhibitory effect of this drug on basal and epinephrine-stimulated lipolysis in adipocytes in VC and SC fat depots. In summary, despite different fat depots eliciting distinct rates of lipolysis, acute AICAR-induced AMPK activation suppressed HSL phosphorylation/activation and exerted similar antilipolytic effects on both VC and SC adipocytes.
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PMID:Regulation of visceral and subcutaneous adipocyte lipolysis by acute AICAR-induced AMPK activation. 1921 74

ACSL1 (acyl-CoA synthetase 1), the major acyl-CoA synthetase of adipocytes, has been proposed to function in adipocytes as mediating free fatty acid influx, esterification, and storage as triglyceride. To test this hypothesis, ACSL1 was stably silenced (knockdown (kd)) in 3T3-L1 cells, differentiated into adipocytes, and evaluated for changes in lipid metabolism. Surprisingly, ACSL1-silenced adipocytes exhibited no significant changes in basal or insulin-stimulated long-chain fatty acid uptake, lipid droplet size, or tri-, di-, or monoacylglycerol levels when compared with a control adipocyte line. However, ACSL1 kd adipocytes displayed a 7-fold increase in basal and a approximately 15% increase in forskolin-stimulated fatty acid efflux without any change in glycerol release, indicating a role for the protein in fatty acid reesterification following lipolysis. Consistent with this proposition, ACSL1 kd cells exhibited a decrease in activation and phosphorylation of AMP-activated protein kinase and its primary substrate acetyl-CoA carboxylase. Moreover, ACSL1 kd adipocytes displayed an increase in phosphorylated protein kinase C and phosphorylated JNK, attenuated insulin signaling, and a decrease in insulin-stimulated glucose uptake. These findings identify a primary role of ACSL1 in adipocytes not in control of lipid influx, as previously considered, but in lipid efflux and fatty acid-induced insulin resistance.
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PMID:Functional analysis of long-chain acyl-CoA synthetase 1 in 3T3-L1 adipocytes. 1942 76

During moderate-intensity exercise, fatty acids are the predominant substrate for working skeletal muscle. The release of fatty acids from adipose tissue stores, combined with the ability of skeletal muscle to actively fine tune the gradient between fatty acid and carbohydrate metabolism, depending on substrate availability and energetic demands, requires a coordinated system of metabolic control. Over the past decade, since the discovery that AMP-activated protein kinase (AMPK) was increased in accordance with exercise intensity, there has been significant interest in the proposed role of this ancient stress-sensing kinase as a critical integrative switch controlling metabolic responses during exercise. In this review, studies examining the role of AMPK as a regulator of fatty acid metabolism in both adipose tissue and skeletal muscle during exercise will be discussed. Exercise induces activation of AMPK in adipocytes and regulates triglyceride hydrolysis and esterfication through phosphorylation of hormone sensitive lipase (HSL) and glycerol-3-phosphate acyl-transferase, respectively. In skeletal muscle, exercise-induced activation of AMPK is associated with increases in fatty acid uptake, phosphorylation of HSL, and increased fatty acid oxidation, which is thought to occur via the acetyl-CoA carboxylase-malony-CoA-CPT-1 signalling axis. Despite the importance of AMPK in regulating fatty acid metabolism under resting conditions, recent evidence from transgenic models of AMPK deficiency suggest that alternative signalling pathways may also be important for the control of fatty acid metabolism during exercise.
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PMID:Role of the AMP-activated protein kinase in regulating fatty acid metabolism during exercise. 1944 92


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