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Lipoxygenase inhibitors inhibit heparin-releasable lipoprotein lipase activity in 3T3-L1 adipocytes and enhance body fat reduction in mice by conjugated linoleic acid
Authors:Yeonhwa Park  Michael W Pariza
Institution:Department of Food Microbiology and Toxicology, Food Research Institute, University of Wisconsin – Madison, 1925 Willow Drive, Madison, WI 53706, USA
Abstract:The t10c12 isomer of conjugated linoleic acid (CLA) reduces lipid accumulation in adipocytes in part by inhibiting heparin-releasable lipoprotein lipase (LPL) activity. We now show that inhibitors of lipoxygenase (LOX) activity (2-12-hydroxydodeca-5,10-diynyl]-3,5,6-trimethyl-p-benzoquinone; 5,8,11,14-eicosatetraynoic acid; salicylhydroxamic acid; indomethacin; nordihydroguaiaretic acid (NDGA)) produce a similar inhibitory effect on LPL activity in cultured 3T3-L1 mouse adipocytes. Additionally the LOX inhibitors had no effect on, or inhibited, lipolysis in this cell system (measured as glycerol release). Growing mice fed diet containing 0.1% NDGA for 4 weeks displayed 21% reduction in body fat, which was similar to 23% reduction in body fat produced by feeding diet containing a suboptimal amount of CLA (0.1%) for 4 weeks. Feeding diet containing both 0.1% NDGA and 0.1% CLA resulted in 51% reduction in body fat which was accompanied by significant increases in whole body water and protein. Aspirin, an inhibitor of cyclooxygenase 1 and 2, had no effect on LPL activity in 3T3-L1 adipocytes, did not affect body composition when fed to growing mice, and failed to influence the effects of CLA on LPL activity in 3T3-L1 cells or body composition in mice. These findings appear to provide new perspectives and insights into the relationships between CLA, eicosanoids, the control of lipid accumulation in adipocytes, and effects of CLA on the immune system.
Keywords:Conjugated linoleic acid  Lipoprotein lipase  Lipoxygenase  Cyclooxygenase  3T3-L1  Adipocyte  Mouse  CLA  conjugated linoleic acid  LPL  heparin-releasable lipoprotein lipase  LOX  lipoxygenase  COX  cyclooxygenase  ECW  empty carcass weight  aspirin  acetylsalicylic acid  NDGA  nordihydroguaiaretic acid  AA861  2-[12-hydroxydodeca-5  10-diynyl]-3  5  6-trimethyl-p-benzoquinone  ETYA  5  8  11  14-eicosatetraynoic acid  SHA  salicylhydroxamic acid  FFA  free fatty acid  SCD  stearoyl-CoA desaturase  HODEs  hydroxyoctadecadienoic acids  HETEs  hydroxyeicosatetraenoic acids
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