title: Protective Effects of 2-Dodecyl-6-Methoxycyclohexa-2,5 -Diene-1,4-Dione Isolated from Averrhoa Carambola L. (Oxalidaceae) Roots on High-Fat Diet-Induced Obesity and Insulin Resistance in Mice.
abstract: OBJECTIVE
  The roots of Averrhoa carambola L. (Oxalidaceae) have long been used as a traditional Chinese medicine for the treatment of diabetes and diabetes-related diseases. 2-dodecyl-6-methoxycycyclohexa-2,5-1,4-dione (DMDD) has been isolated from A. carambola L. roots, and this study was carried out to investigate the potential beneficial effects of DMDD on obesity and insulin resistance induced by a high-fat diet (HFD) in mice.
  
  
  METHODS
  C57BL/6J mice were fed a HFD for 16 weeks and orally administered DMDD (12.5, 25, or 50 mg/kg of body weight per day) and metformin (280 mg/kg of body weight per day) for the last 4 weeks.
  
  
  RESULTS
  The body weights and adipose tissue weights as well as the serum levels of blood glucose, total cholesterol, triglycerides, free fatty acids, insulin, interleukin-6, and tumor necrosis factor-α were significantly decreased by DMDD, and the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor (Myd88) in the epididymal adipose tissue was downregulated by DMDD. In contrast, insulin sensitivity was enhanced. The results of the glucose tolerance tests, insulin tolerance tests, and insulin release tests indicated that there was a marked improvement in insulin secretion, and the areas under the curve corresponding to the three tests were also significantly decreased by DMDD. The activities of superoxide dismutase and glutathione peroxidase were simultaneously enhanced, whereas the content of malondialdehyde was decreased by DMDD in the liver homogenates of the C57BL/6J mice. In addition, hepatic steatosis and adipocyte hypertrophy, as assessed by H&amp;E staining of liver and adipose tissues, were significantly improved by DMDD.
  
  
  CONCLUSIONS
  These data suggest that MDD has potential benefits for the treatment of HFD-induced obesity and insulin resistance, and its effects may be associated with improvements in lipid metabolism and inhibition of the expression of TLR4 in adipose tissues.
authors.affiliation: Department of Pharmacology, Guangxi Medical University, Nanning, PR China.
authors.forename: Juman
authors.initials: J
authors.lastname: Li
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wei
authors.forename: Qiuqiao
authors.initials: Q
authors.lastname: Xie
authors.forename: Thi Thai
authors.initials: TT
authors.lastname: Hoa Pham
authors.forename: Jinbin
authors.initials: J
authors.lastname: Wei
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Xu
authors.forename: Thi Huong
authors.initials: TH
authors.lastname: Giang Nguyen
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Wen
authors.forename: Renbin
authors.initials: R
authors.lastname: Huang
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D065826:Averrhoa / Q000737:chemistry*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D053138:Cyclohexenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D005215:Fasting; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D005247:Feeding Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D009929:Organ Size / Q000187:drug effects; D008517:Phytotherapy; D018517:Plant Roots / Q000737:chemistry*; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: C581182:2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione; D000975:Antioxidants; D001786:Blood Glucose; D053138:Cyclohexenes; D016207:Cytokines; D007328:Insulin; D008055:Lipids; D053594:Myeloid Differentiation Factor 88; D020011:Protective Agents; D051197:Toll-Like Receptor 4