%0 Journal Article
%T The Role of Nrf2: Adipocyte Differentiation, Obesity, and Insulin Resistance
%A Hyun-Ae Seo
%A In-Kyu Lee
%J Oxidative Medicine and Cellular Longevity
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/184598
%X Metabolic diseases, such as type 2 diabetes and obesity, are increasing globally, and much work has been performed to elucidate the regulatory mechanisms of these diseases. Nuclear factor E2-related factor 2 (Nrf2) is a basic leucine zipper transcription factor that serves as a primary cellular defense against the cytotoxic effects of oxidative stress. Recent studies have proposed a close relationship between oxidative stress and energy metabolism-associated disease. The Nrf2 pathway, as a master regulator of cellular defense against oxidative stress, has emerged as a critical target of energy metabolism; however, its effects are controversial. This review examines the current state of research on the role of Nrf2 on energy metabolism, specifically with respect to its participation in adipocyte differentiation, obesity, and insulin resistance, and discusses the possibility of using Nrf2 as a therapeutic target in the clinic. 1. Introduction Nrf2, a basic leucine zipper transcription factor, is encoded by the NFE2L2 gene in humans [1]. Under normal conditions, Nrf2 is sequestered in the cytoplasm by associating with kelch-like ECH-associated protein 1 (Keap1) and cullin 3. Cullin 3 ubiquitinates Nrf2. Keap1 is a substrate of cullin 3, which facilitates the ubiquitination of cullin 3 [2]. During oxidative stress, Keap1 senses cellular oxidative stress and releases Nrf2, at which time Nrf2 travels to the nucleus. In the nucleus, Nrf2 forms a complex with Maf and Jun proteins and binds to the antioxidant response element (ARE) in the upstream promoter region found in many antioxidative genes which initiate their transcription [3]. In this way, Nrf2 is working as a primary cellular defender against the cytotoxic effects of oxidative stress. Oxidative stress results in the development of many diseases, including neurodegenerative diseases, tumors, and metabolic syndromes [4]. Recent studies have shown that oxidative stress is closely associated with energy metabolism [5¨C9]. When obese mice are treated with an NADPH oxidase inhibitor, reactive oxygen species (ROS) production in adipose tissue is reduced, adipocytokine dysregulation is attenuated, and diabetes, hyperlipidemia, and hepatic steatosis are improved [5]. Systemic oxidative stress leads to a lower aerobic capacity and impaired skeletal muscle energy metabolism in patients with metabolic syndrome [6]. Obese people exhibit an increase in systemic oxidative stress [8]. When obese people were subjected to restricted energy intake, oxidative stress marker levels were lower and antioxidant levels were
%U http://www.hindawi.com/journals/omcl/2013/184598/