title: NO-1886 inhibits size of adipocytes, suppresses plasma levels of tumor necrosis factor-alpha and free fatty acids, improves glucose metabolism in high-fat/high-sucrose-fed miniature pigs.
abstract: The synthetic compound NO-1886 is a lipoprotein lipase activator that has been proven to be highly effective in lowering plasma triglycerides and elevating high-density lipoprotein cholesterol. Recently, we found that NO-1886 also had a plasma glucose-reducing action in high-fat/high-sucrose diet-induced diabetic rabbits. In the current study, we investigated the effects of NO-1886 on the morphology of adipocytes, plasma levels of tumor necrosis factor-alpha (TNF-alpha) and free fatty acids (FFA) in miniature pigs fed a high-fat/high-sucrose diet. Our results showed that feeding a high-fat/high-sucrose diet to miniature pigs increased the size of adipocytes, and the plasma levels of TNF-alpha, FFA, and glucose. This diet also induced insulin resistance and impaired the acute insulin response to glucose loading. Supplementing 1% NO-1886 to the high-fat/high-sucrose diet inhibited adipocyte enlargement, and suppressed plasma levels of TNF-alpha, FFA, and glucose. The decrease in plasma TNF-alpha and FFA was simultaneous with the decrease in plasma glucose. We also found an increased whole body glucose clearance and an increased acute insulin response to intravenous glucose loading by NO-1886 supplementation. These data suggest that NO-1886 improves the glucose metabolism in high-fat/high-sucrose diet-induced diabetic minipigs by decreasing fat deposit, and suppressing plasma TNF-alpha and FFA levels. Therefore, NO-1886 is potentially beneficial for the treatment of insulin-resistant syndrome.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanhua University School of Life Sciences and Technology, Hengyang, 421001, Hunan, China. wdy20012001@yahoo.com
authors.forename: Weidong
authors.initials: W
authors.lastname: Yin
authors.forename: Duanfang
authors.initials: D
authors.lastname: Liao
authors.forename: Zongbao
authors.initials: Z
authors.lastname: Wang
authors.forename: Shoumin
authors.initials: S
authors.lastname: Xi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tsutsumi
authors.forename: Tomonari
authors.initials: T
authors.lastname: Koike
authors.forename: Jianglin
authors.initials: J
authors.lastname: Fan
authors.forename: Guanghui
authors.initials: G
authors.lastname: Yi
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Zhang
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Yuan
authors.forename: Kechao
authors.initials: K
authors.lastname: Tang
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D004041:Dietary Fats / Q000008:administration & dosage*; D019422:Dietary Sucrose / Q000008:administration & dosage*; D005230:Fatty Acids, Nonesterified / Q000037:antagonists & inhibitors* / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006131:Growth Inhibitors / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D013552:Swine; D013556:Swine, Miniature; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001549:Benzamides; D004041:Dietary Fats; D019422:Dietary Sucrose; D005230:Fatty Acids, Nonesterified; D006131:Growth Inhibitors; D000960:Hypolipidemic Agents; D009943:Organophosphorus Compounds; D014409:Tumor Necrosis Factor-alpha; C082137:4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide; D005947:Glucose