title: Pioglitazone-induced body weight gain is prevented by combined administration with the lipoprotein lipase activator NO-1886.
abstract: Pioglitazone improves insulin resistance in diabetics but often causes body weight gain. The lipoprotein lipase activator NO-1886 has been shown to exert both anti-obesity and anti-insulin-resistance effects. In this study, we investigated the effect of the combined administration of pioglitazone with NO-1886 (pioglitazone+NO-1886) in preventing body weight gain in insulin-resistant, high-fat fed rats. The rats were fed a standard or high-fat diet for 16 weeks. The high-fat fed rats were randomized at week 9 into 4 groups (i.e., control, pioglitazone (30 mg/kg/day), NO-1886 (100mg/kg/day), and pioglitazone+NO-1886 (30 and 100mg/kg/day, respectively)). The high-fat fed control rats developed obesity and insulin resistance. After 7 weeks of drug treatment, pioglitazone+NO-1886 was found to prevent the body weight gain caused by pioglitazone alone (pioglitazone+NO-1886: Δ76.0 ± 16.8 g vs. pioglitazone: Δ127.8 ± 39.5 g, P<0.05) and to increase glucose infusion rate during insulin clamp, compared with the results in the high-fat fed control group. No differences in plasma nonesterified fatty acid, leptin, adiponectin, glucose, or insulin levels were observed between the pioglitazone+NO-1886 and the pioglitazone-alone groups. However, plasma total cholesterol and HDL-cholesterol levels were significantly increased and plasma triglyceride levels were slightly decreased in the pioglitazone+NO-1886 group, compared with the values in the pioglitazone-alone group. In summary, the combined administration of pioglitazone and NO-1886 prevented the pioglitazone-induced body weight gains and ameliorated insulin resistance observed in high-fat fed rats. These results indicate that combined therapy with pioglitazone and NO-1886 may be beneficial for the treatment of type 2 diabetes.
authors.affiliation: Department of Internal Medicine, Medical Clinic, Aichi Medical University, 2-12-1, Higashisakura, Higashi-ku, Nagoya 461-0005, Japan. info@tonyo.jp
authors.forename: Masataka
authors.initials: M
authors.lastname: Kusunoki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tsutsumi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sato
authors.forename: Aki
authors.initials: A
authors.lastname: Nakamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Habu
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Mori
authors.forename: Munehiko
authors.initials: M
authors.lastname: Morishita
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yonemoto
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miyata
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakaya
authors.forename: Takao
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D050153:Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D052242:Adiponectin / Q000097:blood; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage* / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects*; D004338:Drug Combinations; D004435:Eating / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008297:Male; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000494:pharmacology*; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors*
chemical_list: D052242:Adiponectin; D001549:Benzamides; D001786:Blood Glucose; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D008055:Lipids; D009943:Organophosphorus Compounds; D045162:Thiazolidinediones; C082137:4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide; D008071:Lipoprotein Lipase; D000077205:Pioglitazone