Effects of pioglitazone on increases in visceral fat accumulation and oxidative stress in spontaneously hypertensive hyperlipidemic rats fed a high-fat diet and sucrose solution.
We examined oxidative stress and metabolic characteristics of the spontaneously hypertensive hyperlipidemic rat (SHHR) when it was fed a high-fat diet and sucrose solution (HFDS) after N(G)-nitro-L-arginine methyl ester ingestion to develop a rat model of metabolic syndrome. This study was carried out to assess the effects of pioglitazone on levels of lipid peroxide (LPO), Cu,Zn superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GPx), and non-esterified fatty acids (NEFA) in the plasma and liver tissue in HFDS-SHHR compared with Sprague-Dawley rats (SD). In the HFDS-treated groups, levels of LPO, CAT, GPx, and NEFA were elevated and levels of Cu,Zn-SOD were reduced in the plasma and liver tissue, with a marked accumulation of visceral fat. The changes induced by HFDS feeding were severe in the SHHR model that had essential hypertension and hyperlipidemia, when compared with SD that did not have these essential risk factors. Subcutaneous injection of 10 mg/kg per day of pioglitazone for 2 months significantly restored levels of LPO, CAT, GPx, Cu,Zn-SOD, and NEFA in the HFDS-SHHR group, and visceral fat accumulation was reduced. These results suggest that HFDS-SHHR is a suitable model of metabolic syndrome and that pioglitazone treatment can improve oxidative dysregulation in this rat model.
Saiki
Ryo
R
Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan. ryou-777@zj8.so-net.ne.jp
Okazaki
Masako
M
Iwai
Shinichi
S
Kumai
Toshio
T
Kobayashi
Shinichi
S
Oguchi
Katsuji
K
D000818:Animals; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D004041:Dietary Fats; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D006949:Hyperlipidemias / Q000150:complications; D006973:Hypertension / Q000150:complications; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects*; D000077205:Pioglitazone; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D013395:Sucrose; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*
D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D008054:Lipid Peroxides; D045162:Thiazolidinediones; D013395:Sucrose; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000077205:Pioglitazone