Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Diabetes. May 15, 2012; 3(5): 94-104
Published online May 15, 2012. doi: 10.4239/wjd.v3.i5.94
Curcumin attenuates Nrf2 signaling defect, oxidative stress in muscle and glucose intolerance in high fat diet-fed mice
Hui-Jun He, Guo-Yu Wang, Yuan Gao, Wen-Hua Ling, Zhi-Wen Yu, Tian-Ru Jin
Hui-Jun He, Guo-Yu Wang, Yuan Gao, Wen-Hua Ling, Zhi-Wen Yu, Tian-Ru Jin, Department of Nutrition, School of Public Health, Sun Yat-sen University, Room 517, 74 Zhongshan 2nd Road, Guangzhou 510080, Guangdong Province, China
Author contributions: He HJ performed the experiments throughout the study and wrote the draft of this manuscript; Wang GY and Gao Y participated in the intraperitoneal glucose tolerance test experiments and mice tissue collection; Ling WH provided his advice on HFD feeding and the dosage of curcumin in this study; Yu ZW designed the study, provided technical guidance and edited this paper; Jin TR coordinated the study, provided important guidance and final editing of the manuscript.
Supported by A National Natural Science Foundation of China Grant, No. 81072300 to Jin TR and Yu ZW
Correspondence to: Dr. Zhi-Wen Yu, Associate Professor, Department of Nutrition, School of Public Health, Sun Yat-sen University, Room 517, 74 Zhongshan 2nd Road, Guangzhou 510080, Guangdong Province, China. yuzhiwen@yahoo.com
Telephone: +86-20-87330625 Fax: +86-20-87330446
Received: January 29, 2012
Revised: April 19, 2012
Accepted: May 11, 2012
Published online: May 15, 2012
Abstract

AIM: To investigate the signaling mechanism of anti-oxidative action by curcumin and its impact on glucose disposal.

METHODS: Male C57BL/6J mice were fed with either a normal diet (n = 10) or a high fat diet (HFD) (n = 20) to induce obesity and insulin resistance. After 16 wk, 10 HFD-fed mice were further treated with daily curcumin oral gavage at the dose of 50 mg/kg body weight (BW) (HFD + curcumin group). After 15 d of the curcumin supplementation, an intraperitoneal glucose tolerance test was performed. Fasting blood samples were also collected for insulin and glucose measurements. Insulin-sensitive tissues, including muscle, adipose tissue and the liver, were isolated for the assessments of malondialdehyde (MDA), reactive oxygen species (ROS) and nuclear factor erythroid-2-related factor-2 (Nrf2) signaling.

RESULTS: We show here that in a HFD mouse model, short-term curcumin gavage attenuated glucose intolerance without affecting HFD-induced BW gain. Curcumin also attenuated HFD-induced elevations of MDA and ROS in the skeletal muscle, particularly in its mitochondrial fraction, but it had no such an effect in either adipose tissue or the liver of HFD-fed mice. Correspondingly, in skeletal muscle, the levels of total or nuclear content of Nrf2, as well as its downstream target, heme oxygenase-1, were reduced by HFD-feeding. Curcumin intervention dramatically reversed these defects in Nrf2 signaling. Further analysis of the relationship of oxidative stress with glucose level by a regression analysis showed a positive and significant correlation between the area under the curve of a glucose tolerance test with MDA levels either in muscle or muscular mitochondria.

CONCLUSION: These findings suggest that the short-term treatment of curcumin in HFD-fed mice effectively ameliorates muscular oxidative stress by activating Nrf2 function that is a novel mechanism for its effect in improving glucose intolerance.

Keywords: Oxidative stress; Insulin resistance; Glucose tolerance; Nuclear factor erythroid-2-related factor-2; Curcumin; Mitochondria