Novel Strategies for Treating Lifestyle-related Diseases Using Various Approaches.

The number of patients with metabolic disorders is dramatically increasing all over the world. The diseases often exhibit multiple metabolic disturbances including diabetes, hyperlipidemia, and obesity, and so on, recognized as a concept of metabolic syndrome. It is important to consider the common underlying pathophysiological bases of such metabolic diseases at the suggestion of the teachings of a parable, "The blind men and an elephant," whereby each blind man investigates a different part of the elephant. The lesson could even be applicable to each aspect of the disorders. Physical exercise as well as dietetics harbor versatile preventive and therapeutic potency against diverse metabolic diseases. Thus further investigation into molecular and physiological mechanisms underlying beneficial effects of therapeutic exercise and diet will provide us with significant clues to the elephant behind the disorders. Moreover, it could be of great benefit if such non-drug treatments, which may be hard to achieve for most patients, were replaced with medication. Recently, we demonstrated evidence that activators of 5'AMP-activated protein kinase (AMPK) could be satisfactory exercise mimetics in terms of metabolome. In this review, metabolomic analysis on the significant roles of AMPK in contracting skeletal muscles is described. In addition, our novel prodrug strategy providing extremely hydrophobic agents with marked hydrophilicity by conjugation with branched glycerol oligomers, which can be widely applicable in general to drug design for good pharmacokinetic properties in drug discovery, is introduced.