Metabolic diseases, such as insulin resistance, type II diabetes, and obesity, are associated with a low-grade chronic inflammation (inflammatory stress), oxidative stress, and endoplasmic reticulum (ER) stress. Because the integration of these stresses is critical to the pathogenesis of metabolic diseases, agents and cellular molecules that can modulate these stress responses are emerging as potential targets for intervention and treatment of metabolic diseases. It has been recognized that heme oxygenase-1 (HO-1) plays an important role in cellular protection. Because HO-1 can reduce inflammatory stress, oxidative stress, and ER stress, in part by exerting antioxidant, anti-inflammatory, and antiapoptotic effects, HO-1 has been suggested to play important roles in pathogenesis of metabolic diseases. In the present review, we will explore our current understanding of the protective mechanisms of HO-1 in metabolic diseases and present some emerging therapeutic options for HO-1 expression in treating metabolic diseases, together with the therapeutic potential of curcumin and resveratrol analogues that have their ability to induce HO-1 expression. 1. Introduction The clustering in an individual of multiple metabolic abnormalities associated with metabolic diseases, including insulin resistance (IR), type II diabetes (T2D), and obesity, is defined as the metabolic syndrome (MS) [1]. It is well accepted that MS increases the risk of developing cardiovascular disease (CVD) [2]. Although there is a therapeutic treatment to combat some of metabolic diseases, especially T2D and CVD, both the intake of proper diets and maintaining healthy lifestyles are considered the best preventive measures [3]. However, for patients with MS, it is difficult to follow a diet/exercise regime that would improve their symptoms. Therefore, the identification of agents that may deal with more serious aspects of MS is an important medical field for research. Numerous experimental studies have confirmed the important role of naturally occurring phytochemicals in prevention and treatment of metabolic diseases [4]. Curcumin (Cur), resveratrol (Res), and their related derivatives are the most studied compounds in these fields so far [5]; therefore, we will discuss the therapeutic usage of Cur and Res in the context of metabolic diseases, together with the underlying mechanisms of action. Recent studies have suggested that almost all of metabolic diseases are associated with a low-grade chronic inflammation (hereafter referred as to inflammatory stress), oxidative stress, and endoplasmic
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