Approaches to Pathogeneses of Metabolic Syndrome

- A biological candidate approach vs. random searches

Lee-Ming Chuang, MD, PhD

Department of Internal Medicine & Graduate Institute of Clinical Medicine,

National Taiwan University School of Medicine, Taipei, TAIWAN

Metabolic syndrome, a clinical disorder consisting of clustering of obesity, hypertension, type 2 diabetes and coronary artery disease, becomes the most common health problem in recent years. The underlying causes of this complex disorder are multi-factorial including multiple environmental and genetic factors. Despite of extensive research, the underlying molecular defects remains to be further elucidated.

Both biological candidate and random search approaches to the multifactorial disorders are employed trying to tease out the complex pathogenetic pathways of the MS. Adipose tissue serves as a good biologic candidate because epidemiological observations have shown obesity esp. visceral adiposity are the most predictive factors for the development of hypertension and type 2 diabetes. Therefore, genes involved in adipogenesis might relate to insulin sensitivity/resistance. Studies have been able to show the genes either profoundly secreted by adipocytes or genes with differential expression during adipocyte differentiation shed new light to link those biological candidates to insulin resistance in human disorders. On the other hand, random genome-wide linkage analyses also help identify the candidate genes involved in type 2 diabetes and obesity. Moreover, QTLs that contribute to the variance of insulin resistance and plasma adiponectin level, a novel surrogate of insulin resistance, might help elucidate the important genes that involve in insulin resistance.

In this presentation, we confirmed that multiple genes including adiponectin were related to insulin resistance and metabolic syndrome in humans. Future development targeting this gene might be beneficial for treatment of the subjects with metabolic syndrome in the future.