ABSTRACT

Metabolic syndrome (MetS) is characterized by accumulation of visceral fat associated with the clustering of metabolic and pathophysiological cardiovascular risk factors: impaired glucose tolerance (IGT) or diabetes mellitus (DM), dyslipidemia, and hypertension (HTN) (Fujioka et al. 1987). The prevalence of MetS is rapidly increasing worldwide not only in industrialized countries but also in developing countries associated with a change in the lifestyle as exemplied by an increase in food intake and a decrease in exercise. Accumulation of visceral fat creates a chain reaction of risk factors for life-threatening cardiovascular diseases (CVD) such as myocardial infarction (MI) and

17.1 Epidemiology of MetS .......................................................................................................... 325 17.2 Pathophysiology of MetS ...................................................................................................... 327

17.2.1 Dysregulation of Adipocytokines ............................................................................. 327 17.2.2 Insulin Resistance ..................................................................................................... 329 17.2.3 Hypertension ............................................................................................................. 330 17.2.4 Atherosclerosis .......................................................................................................... 331 17.2.5 Obstructive Sleep Apnea .......................................................................................... 331

17.3 Therapeutic Strategies for MetS ........................................................................................... 333 17.3.1 Calorie Restriction .................................................................................................... 333 17.3.2 Exercise ..................................................................................................................... 336 17.3.3 Current Pharmacological Tools for MetS and Lifestyle-Related Diseases .............. 338

17.3.3.1 Antihypertension Drugs ............................................................................. 338 17.3.3.2 Antidiabetic Agents ................................................................................... 339 17.3.3.3 Anti-Dyslipidemic Agents ......................................................................... 341 17.3.3.4 Antioxidants ............................................................................................... 342

17.3.4 Calorie Restriction Mimetic Agents .........................................................................344 17.3.4.1 Resveratrol .................................................................................................344 17.3.4.2 SIRT1 Activators ........................................................................................346 17.3.4.3 Rapamycin ................................................................................................. 347 17.3.4.4 Tetrahydrobiopterin.................................................................................... 347 17.3.4.5 Appetite Suppressants ................................................................................ 349

17.4 Conclusions ........................................................................................................................... 350 Abbreviations ................................................................................................................................. 350 Acknowledgments .......................................................................................................................... 351 References ...................................................................................................................................... 351

stroke. This phenomenon has been termed “metabolic domino” (Itoh 2006), a process similar to falling dominoes. Figure 17.1 illustrates the sequence of events that begins with the lifestyle to promote accumulation of visceral fat in conjunction with predisposition, leading to fatty liver diseases and devastating CVD. Accordingly, lifestyle intervention and pharmacotherapy are imperative to block falling of the dominoes as upstream as possible.