| 摘要 |
Anti-inflammatory effect of α-MSH-like compounds can be employed for curtailing sequelae of obesity and overweight. Importantly, molecular compounds that stimulate melanin biosynthesis by mimicking the effects of α-MSH are readily available for trials aimed at control of metabolic syndrome components. Synthetic agonists of α-MSH receptors, melanotan II and bremelanotide, have already been proven safe in human trials for therapeutic tanning and some non-obesity-related diseases. The abatement of the non-communicable age-related diseases (NCDs) such as heart disease, cancer, stroke, type 2 diabetes and chronic lower respiratory diseases is a global challenge assigned high priority by The World Health Organization (WHO) [1]. Tobacco smoking, physical inactivity and the resulting obesity are established risk factors for many NCDs. The pathogenesis of NCDs is complex. Moreover, each chronic illness of NCD type cannot be considered in isolation as they share common, usually related risk factors [2]. This observation indicates that integrated strategies can be effective for many different conditions [3]. One common factor that initiates or hastens progression of almost all NCDs is a systemic low-grade inflammation. Both chronic inflammation and reactive oxygen species (ROS) are also key features of ageing. The interaction between inflammatory and insulin/IGF-1 signaling pathways is well established; in that, subclinical inflammation increases insulin resistance. In overweight and obese populations prevalent in the US, the subclinical inflammation propagates by the excessive adipocytic production of the pro-inflammatory cytokines including TNF-α and IL-6, possibly compounded by the infiltration of adipose by macrophages [6]. In turn, the cytokine production by adipocytes and macrophages contributes to obesity-related insulin resistance, thus, propagating the greatest vicious circle of NCDs.
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