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)

We have recently reported that intake of soya protein isolate (SPI) inhibited the DNA-binding activities of hepatic thyroid hormone receptor (TR). The genes for acetyl-CoA carboxylase (ACC), a rate-limiting enzyme in fatty acid synthesis, contain the thyroid hormone response element in their promoters and are regulated by TR. The present study has examined the effect of long-term feeding of SPI and soya isoflavones (ISF) on the gene expression and protein phosphorylation of different ACC isoforms in different tissues and plasma triacylglycerol (TAG) levels in rats. Sprague-Dawley female rats were fed diets containing 20 % casein or alcohol-washed SPI with or without supplemental ISF for 70, 190 and 310 d. SPI intake significantly reduced plasma TAG concentrations compared with casein, whereas supplemental ISF had no effect. Hepatic ACCalpha and ACCbeta mRNA abundance and protein content were markedly lower in the rats fed SPI than in those fed casein. The protein contents of ACCalpha in the kidney and ACCbeta, the predominant isoform in the heart and kidney, were unchanged by dietary SPI. The ratios of phospho-ACCalpha/ACCalpha and phospho-ACCbeta/ACCbeta were not different among dietary groups in all tissues measured. The present study demonstrates that ingestion of SPI decreases plasma TAG level and down-regulates ACCalpha and ACCbeta gene expression in the liver but not in the heart and kidney. The results indicate that the effect of SPI is tissue-specific and that alteration of ACC gene expression rather than phosphorylation status may play a major role in the regulation of ACC activities by soya proteins.
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PMID:Tissue-specific regulation of acetyl-CoA carboxylase gene expression by dietary soya protein isolate in rats. 1676 25

Antiobesity drugs that target peripheral metabolism may avoid some of the problems that have been encountered with centrally acting anorectic drugs. Moreover, if they cause weight loss by increasing fat oxidation, they not only address a cause of obesity but also should promote loss of fat rather than lean tissue and improve insulin sensitivity. Weight loss may be slow but more sustained than with anorectic drugs, and thermogenesis may be insufficient to cause any discomfort. Some thermogenic approaches are the activation of adrenergic, thyroid hormone or growth hormone receptors and the inhibition of glucocorticoid receptors; the modulation of transcription factors [e.g. peroxisome proliferator-activated receptor delta (PPARdelta) activators] or enzymes [e.g. glutamine fructose-6-phosphate amidotransferase (GFAT) inhibitors] that promote mitochondrial biogenesis, and the modulation of transcription factors (PPAR alpha activators) or enzymes (AMP-activated protein kinase) that promote fatty acid oxidation. More surprisingly, studies on genetically modified animals and with enzyme inhibitors suggest that inhibitors of fatty acid synthesis [e.g. ATP citrate lyase, fatty acid synthase, acetyl-CoA carboxylase (ACC)], fatty acid interconversion [stearoyl-CoA desaturase (SCD)] and triglyceride synthesis (e.g. acyl-CoA : diacylglycerol acyltransferase) may all be thermogenic. Some targets have been validated only by deleting genes in the whole animal. In these cases, it is possible that deletion of the protein in the brain is responsible for the effect on adiposity, and therefore a centrally penetrant drug would be required. Moreover, whilst a genetically modified mouse may display resistance to obesity in response to a high fat diet, it requires a tool compound to demonstrate that a drug might actually cause weight loss. Even then, it is possible that differences between rodents and humans, such as the greater thermogenic capacity of rodents, may give a misleading impression of the potential of a drug.
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PMID:Thermogenic and metabolic antiobesity drugs: rationale and opportunities. 1739 Nov 51


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