title: [Effects of soluble epoxide hydrolase inhibitors on lipid metabolism and secretive functions of adipocytes].
abstract: OBJECTIVE
  To observe the effects of soluble epoxide hydrolase inhibitors-tAUCB on the uptake and degradation of ox-LDL in adipocytes.
  
  
  METHODS
  3T3-L1 preadipocytes were induced into differentiation and maturation. After a 24-hour starvation, the cells were stimulated with 100 ng/ml LPS and then tAUCB at various concentrations (0 - 100 µmol/L)were added for 24 h, or preincubated with the PPARγ (peroxisome proliferators activated receptor gamma) antagonist GW9662 (5 µmol/L). And the 0 µmol/L tAUCB-treated group was taken as the blank control group. Then the uptake and degradation of ox-LDL in cells were measured by radioligand assay. The mRNA expressions of PPARγ and CD36 were detected by real-time PCR (polymerase chain reaction). And the intracellular levels of protein expression of PPARγ and CD36 were detected by Western blot. While ADP and TNF-α in supernatant were detected by ELISA.
  
  
  RESULTS
  tAUCB could dose-dependently increase the uptake and degradation of ox-LDL in adipocytes. When stimulated with 10, 50, 100 µmol/L tAUCB, the uptake levels of ox-LDL were (35.6 ± 1.1)ng/mg, (39.8 ± 1.6) ng/mg, (42.6 ± 1.4) ng/mg cell protein and the degradation levels of ox-LDL (2879 ± 54) ng/mg, (3082 ± 56) ng/mg, (3226 ± 68) ng/mg cell protein. And they were significantly higher than those of the control group (28.9 ± 1.2) ng/mg, (2791 ± 54) ng/mg respectively (all P < 0.05). However, after preincubation of GW9662, the uptake of ox-LDL were decreased to (30.6 ± 1.3) ng/mg, (31.1 ± 1.7) ng/mg, (32.1 ± 1.8) ng/mg cell protein whereas the degradation of ox-LDL decreased to (2788 ± 53) ng/mg, (2824 ± 70) ng/mg, (2874 ± 70) ng/mg cell protein. And the difference was statistically significant when it was compared with the corresponding tAUCB-treated group. With the rising concentration of tAUCB, tAUCB could dose-dependently increase the mRNA and protein expression of CD36 and PPARγ. tAUCB could dose-dependently decrease the levels of TNF-α and increase the levels of ADP in adipocytes. GW9662 could significantly inhibit those effects of tAUCB and reduce the uptake and degradation of ox-LDL and the expression of PPARγ and CD36 in adipocytes.
  
  
  CONCLUSIONS
  tAUCB can up-regulate the PPARγ expression in adipocytes and promote the uptake and degradation of ox-LDL in adipocytes via PPARγ-CD36 pathway. Meanwhile, the levels of ADP and TNF-α may be mediated through the activation of PPARγ.
authors.affiliation: Department of Cardiology, Internal Medicine, Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Jiang
authors.forename: Dan-Yan
authors.initials: DY
authors.lastname: Xu
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Zhao
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: DU
authors.forename: Dao-Quan
authors.initials: DQ
authors.lastname: Peng
authors.forename: Shui-Ping
authors.initials: SP
authors.lastname: Zhao
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D018955:CD36 Antigens / Q000032:analysis; D002478:Cells, Cultured; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D050356:Lipid Metabolism / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000032:analysis; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C457499:2-chloro-5-nitrobenzanilide; C524106:4-(4-(3-adamantan-1-ylureido)cyclohexyloxy)benzoic acid; D000813:Anilides; D001565:Benzoates; D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D047495:PPAR gamma; C099252:oxidized low density lipoprotein; D014508:Urea; D004851:Epoxide Hydrolases