title: Diethylcarbamazine citrate ameliorates insulin resistance in high-fat diet-induced obese mice via modulation of adipose tissue inflammation.
abstract: Diethylcarbamazine citrate (DEC) had been known as anti-inflammatory drug but its effect on obesity-induced insulin resistance as a result of released inflammatory mediators from adipose tissue (AT) was not known. White male albino mice were fed with high fat diet (HFD) for 18weeks to induce obesity. DEC at different three doses (12, 50 and 200mg/kg) was orally administered twice a week starting at week 6. Body, liver and adipose tissue weights were taken, while glucose tolerance, insulin resistance, blood triglycerides and levels of adipokines (leptin, TNF-α, IL-6 and MCP-1) were tested. The activity of cyclooxygenase (COX) in the liver tissue homogenate was also tested. In addition, NF-κBp65 localization in liver cell cytoplasmic and nuclear fractions was detected using Western blotting. The only effective anti-inflammatory dose was 50mg/kg to reduce (p<0.05) the high levels of glucose, insulin and triglycerides in serum. DEC was not anti-obesity drug because the weights of body, liver and adipose tissues were not changed. Hyperleptinemia was decreased (p<0.001) and associated with a reduction in serum levels of TNF-α, IL-6 and MCP-1 (p<0.001). In addition, the activity of COX in DEC treatment decreased significantly (p<0.01), while NF-κBp65 localization in nuclear extracts was obviously inhibited in 50mg/kg treated group. It could be concluded that DEC was the only effective dose against mouse insulin resistance but not lipid accumulation.
authors.affiliation: Zoology Department, Faculty of Science, Beni-Suef University, 62511 Salah Salem Street, Beni-Suef, Egypt. Electronic address: mahmoud_1232000@yahoo.com.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Abdel-Latif
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects*; D004049:Diethylcarbamazine / Q000494:pharmacology*; D005786:Gene Expression Regulation; D007249:Inflammation / Q000139:chemically induced*; D007333:Insulin Resistance; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D009765:Obesity / Q000139:chemically induced*; D009929:Organ Size; D021381:Protein Transport; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D016859:Lipoxygenase Inhibitors; D051996:Transcription Factor RelA; D004049:Diethylcarbamazine
keywords: Adipose tissue; Diethylcarbamazine citrate; Inflammation; Insulin