Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycerolipid acyltransfereases play important roles in physiological and pathophysiological processes of triglyceride (TAG) metabolism and energy balance. Glycerol-3-phosphate acyltransferases (GPATs) are key enzymes in the triglyceride biosynthetic pathway. In addition to the mitochondrial GPAT1 that was first cloned and studied, novel microsomal enzyme isoforms have been discovered in recent years. The potential function of one of the GPATs, GPAT4, was studied in GPAT4 deficient mice that suggested its role in TAG synthesis in multiple tissues. Monoacylglycerol and diacylglycerol acyltransferases (MGAT2 and DGAT1) are important enzymes involved in intestinal triglyceride absorption, and studies in recent years from knockout mice have revealed their important role in whole body energy metabolism through changes in intestinal TAG absorption kinetics. Both MGAT2 and DGAT1 mice are resistant to dietinduced obesity and have improved insulin sensitivity and hepatic TAG accumulation. These data suggest that these enzymes are intimately involved in TAG metabolism and whole body energy homeostasis and that inhibition of these enzymes may provide therapeutic benefits for metabolic disorders such as obesity, metabolic syndrome, and type 2 diabetes.
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PMID:Glycerolipid acyltransferases in triglyceride metabolism and energy homeostasis-potential as drug targets. 2238 14

The rise in the prevalence of obesity and metabolic syndrome turned NAFLD as the most common cause of chronic liver diseases worldwide. Although the role of toll like receptors, especially TLR4, as activators of inflammatory pathways in liver diseases is well established, our goal was to investigate if TLR4 activation could modulate metabolic lipid pathways and alter the onset of NAFLD. We used LDL receptor-deficient mice (LDLrKO) fed with an atherogenic diet as a model. The role of TLR4 activation was evaluated by crossing LDLrKO mice with the TLR4 knockout mice. Animals were fed for 12weeks with high-fat high-cholesterol diet (HFD) containing 18% saturated fat and 1.25% cholesterol. TLR4/LDLr KO mice presented lower triacylglyceride (TAG) plasma levels when compared to LDLrKO, despite the type of diet ingested. HFD induced TAG and cholesterol accumulation in the liver of all mice genotypes studied, but TLR4/LDLr KO presented lower TAG accumulation than LDLrKO mice. Gene expression of TAG synthesis enzymes (ApoB100, MTTP, GPAT1 and GPAT4) was not differentially altered in TLR4/LDLr KO and LDLrKO mice. On the other hand, TLR4 deficiency enhanced the expression of several enzymes involved in the oxidation of fatty acids, as follows: ACOX, CPT-1, MTPa, MTBb, PBE and 3-ketoacyl-CoA thiolase. Acyl-carnitine plasma profile showed an increase in C0 and C2 concentration in TLR4/LDLr KO group, corroborating the hypothesis of increased fat oxidation. Our results indicate that TLR4 may have an important role in the onset of steatosis, once its depletion enhances fatty acid oxidation in the liver of mice, preventing triglyceride accumulation.
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PMID:Novel role of TLR4 in NAFLD development: Modulation of metabolic enzymes expression. 2617 53