Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.34 (lipoprotein lipase)
 7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Numerous physiological effects are attributed to conjugated linoleic acid (CLA). The purpose of this presentation is to consider these effects with respect to the cis-9,trans-11 and trans-10,cis-12 CLA isomers. We review previously published data and present new findings that relate to underlying biochemical mechanisms of action. Both isomers are natural products. The cis-9,trans-11 isomer is the principal dietary form of CLA, but the concentrations of this isomer and the trans-10,cis-12 isomer in dairy products or beef vary depending on the diet fed to cows or steers, respectively. The trans-10,cis-12 CLA isomer exerts specific effects on adipocytes, in particular reducing the uptake of lipid by inhibiting the activities of lipoprotein lipase and stearoyl-CoA desaturase. The trans-10,cis-12 CLA isomer also affects lipid metabolism in cultured Hep-G2 human liver cells, whereas both the cis-9,trans-11 and trans-10,cis-12 CLA isomers appear to be active in inhibiting carcinogenesis in animal models. We present new findings indicating that the cis-9,trans-11 CLA isomer enhances growth and probably feed efficiency in young rodents. Accordingly, the effects of CLA on body composition (induced by trans-10,cis-12 CLA) and growth/feed efficiency (induced by cis-9,trans-11 CLA) appear to be due to separate biochemical mechanisms. We also show that a 19-carbon CLA cognate (conjugated nonadecadienoic acid, CNA) inhibits lipoprotein lipase activity as effectively as CLA in cultured 3T3-L1 adipocytes. Presumably, CNA is metabolized differently than the 18-carbon CLA isomers, so this finding indicates direct activity of the administered compound as opposed to acting via a metabolite.
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PMID:The biologically active isomers of conjugated linoleic acid. 1141 93

The trans10,cis12 (t10c12) isomer of conjugated linoleic acid (CLA) has been shown to inhibit heparin-releasable lipoprotein lipase activity, reduce lipid stores in cultured 3T3-L1 adipocytes, and, when fed to mice, reduce body fat gain. We now report that t10c12 CLA significantly reduced leptin secretion from cultured 3T3-L1 adipocytes, and reduced leptin mRNA levels within the cells. Similar effects were produced by conjugated nonadecadienoic acid (a 19-carbon CLA cognate that is more effective than CLA in reducing body fat gain in mice), the lipoxygenase inhibitor nordihydroguaiaretic acid (which is synergistic with CLA in reducing body fat gain in mice), and ciglitazone (TZD, a PPARgamma agonist). Feeding mice diet supplemented with 0.5% t10c12 CLA for 4 weeks significantly reduced body fat gain, serum leptin levels and adipocyte leptin mRNA expression, without affecting feed intake or body weight. These data provide new insights into apparent mechanistic similarities among t10c12 CLA, CNA, NDGA, and TZD.
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PMID:trans-10,cis-12-Conjugated linoleic acid reduces leptin secretion from 3T3-L1 adipocytes. 1155 38

The trans-10,cis-12 isomer of conjugated linoleic acid (CLA) has been shown to reduce body fat gain in mice. However, the underlying molecular mechanism is not well characterized. Here we report evidence that trans-10,cis-12 (t10c12) CLA inhibits preadipocyte differentiation. Treating differentiating 3T3-L1 preadipocytes with t10c12 CLA and conjugated nonadecadienoic acid (CNA, a 19-carbon CLA cognate) resulted in decreased intracellular triglyceride accumulation and mRNA levels of the adipogenic gene fatty acid synthase and adipocyte lipid binding protein. T10c12 CLA and CNA also reduced protein levels of adipocyte transcription factors, peroxisome proliferator-activated receptor gamma and CCAAT/enhancer binding protein alpha. Similarly, CLA reduced body fat gain and significantly inhibited the expression of PPAR gamma and its downstream target lipoprotein lipase in mouse adipose tissue. These observations indicate that CLA decreases body fat gain in part by inhibiting the differentiation of preadipocytes.
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PMID:trans-10,cis-12 CLA inhibits differentiation of 3T3-L1 adipocytes and decreases PPAR gamma expression. 1267 Apr 81