Fish oil prevents excessive accumulation of subcutaneous fat caused by an adverse effect of pioglitazone treatment and positively changes adipocytes in KK mice. (2016)

• Record Type: Journal Article
• Authors: Iizuka, Yuzuru; Kim, Hyounju; Nakasatomi, Maki; Izawa, Takuya; Hirako, Satoshi; Matsumoto, Akiyo
• Is Part Of: Toxicology reports. Volume 3(2016)
• Page Start: 4
• Page End: 14
• Publication Date: 2016
• Subjects: AOX acyl-CoA oxidase -- ACC acetyl-CoA carboxylase -- ATM adipose tissue macrophage -- AUC area under the curve -- BAT brown adipose tissue -- CPT-1 carnitine palmitoyl transferase 1 -- CT computed tomography -- DHA docosahexaenoic acid -- ELISA enzyme-linked immunosorbent assay -- EPA eicosapentaenoic acid -- FAS fatty acid synthase -- FFA free fatty acid -- G6pase glucose-6-phosphatase -- GPAT glycerol-3-phosphate acyltransferase -- HDL-C high-density lipoprotein cholesterol -- H&E hematoxylin and eosin -- HOMA-IR homeostasis model assessment of insulin resistance -- Insig-1 insulin-induced gene 1 -- IR insulin resistance -- ITT insulin tolerance test -- MCAD medium-chain acyl-CoA dehydrogenase -- MCP-1 monocyte chemoattractant protein-1 -- OGTT oral glucose tolerance test -- PEPCK phosphoenolpyruvate carboxykinase -- PPARα peroxisome proliferator-activated receptor alpha -- PPARγ peroxisome proliferator-activated receptor gamma -- RT-PCR real-time polymerase chain reaction -- SCD-1 stearoyl-CoA desaturase 1 -- SREBP sterol regulatory element-binding protein -- TNF-α tumor necrosis factor-α -- TLR-4 toll-like receptor-4 -- TZD thiazolidinedione -- UCP-2 uncoupling protein 2 -- VLDL very low-density lipoprotein -- WAT white adipose tissue; Fish oil -- Pioglitazone -- Adverse effect; Toxicology -- Periodicals; Clinical toxicology -- Periodicals; Drug-Related Side Effects and Adverse Reactions; Hazardous Substances; Poisoning; Toxicology; Electronic journals; Periodicals; Periodicals; 571.9505
• DOI: 10.1016/j.toxrep.2015.11.003
• Languages: English
• ISSNs: 2214-7500

Abstract

Abstract: Pioglitazone, a thiazolidinedione (TZD), is widely used as an insulin sensitizer in the treatment of type 2 diabetes. However, body weight gain is frequently observed in TZD-treated patients. Fish oil improves lipid metabolism dysfunction and obesity. In this study, we demonstrated suppression of body weight gain in response to pioglitazone administration by combination therapy of pioglitazone and fish oil in type 2 diabetic KK mice. Male KK mice were fed experimental diets for 8 weeks. In safflower oil (SO), safflower oil/low-dose pioglitazone (S/PL), and safflower oil/high-dose pioglitazone (S/PH) diets, 20% of calories were provided by safflower oil containing 0%, 0.006%, or 0.012% (wt/wt) pioglitazone, respectively. In fish oil (FO), fish oil/low-dose pioglitazone (F/PL), and fish oil/high-dose pioglitazone (F/PH) diets, 20% of calories were provided by a mixture of fish oil and safflower oil. Increased body weight and subcutaneous fat mass were observed in the S/PL and S/PH groups; however, diets containing fish oil were found to ameliorate these changes. Hepatic mRNA levels of lipogenic enzymes were significantly decreased in fish oil-fed groups. These findings demonstrate that the combination of pioglitazone and fish oil decreases subcutaneous fat accumulation, ameliorating pioglitazone-induced body weight gain, through fish oil-mediated inhibition of hepatic de novo lipogenesis.