The primary deficiency underlying metabolic syndrome is insulin resistance, in which insulin-responsive peripheral tissues fail to maintain glucose homeostasis. Because skeletal muscle is the major site for insulin-induced glucose uptake, impairments in skeletal muscle’s insulin responsiveness play a major role in the development of insulin resistance and type 2 diabetes. For example, skeletal muscle of type 2 diabetes patients and their offspring exhibit reduced ratios of slow oxidative muscle. These observations suggest the possibility of applying muscle remodeling to recover insulin sensitivity in metabolic syndrome. Skeletal muscle is highly adaptive to external stimulations such as exercise; however, in practice it is often not practical or possible to enforce the necessary intensity to obtain measurable benefits to the metabolic syndrome patient population. Therefore, identifying molecular targets for inducing muscle remodeling would provide new approaches to treat metabolic syndrome. In this review, the physiological properties of skeletal muscle, genetic analysis of metabolic syndrome in human populations and model organisms, and genetically engineered mouse models will be discussed in regard to the prospect of applying skeletal muscle remodeling as possible therapy for metabolic syndrome. 1. Introduction Are we getting healthier as technology and medicine advance? According to the latest epidemiological study on baby boomers in the United States, unfortunately the answer appears to be “No, we are not” [1]. This study tells us that far more aging baby boomers, compared to the previous generation, are afflicted by lifestyle induced clinical conditions such as hypertension, hypercholesterolemia, type 2 diabetes mellitus, and obesity [1]. Despite these health problems, people are living longer due to medical advances. The steadily increasing life expectancy combined with expanding waist lines presents a daunting challenge for society to maintain a good quality of life in the aging population. The aforementioned clinical conditions, hypertension, hypercholesterolemia, type 2 diabetes mellitus, and obesity, are all symptomatic components of metabolic syndrome. Metabolic syndrome consists of a heterogeneous, but highly interconnected set of clinical conditions which together lead to a high risk of cardiovascular diseases [2]. The World Health Organization (WHO) provided a working definition of metabolic syndrome as the combination of one symptom from group 1 (insulin resistance, type 2 diabetes, impaired fasting glucose, impaired glucose tolerance)
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