Establishment of a concept of visceral fat syndrome and discovery of adiponectin

Abstract

Although obesity is a major background of life style-related diseases such as diabetes mellitus, lipid disorder, hypertension and cardiovascular disease, the extent of whole body fat accumulation does not necessarily the determinant for the occurrence of these diseases. We developed the method for body fat analysis using CT scan and established the concept of visceral fat obesity, in other word metabolic syndrome in which intra-abdominal visceral fat accumulation has an important role in the development of diabetes, lipid disorder, hypertension and atherosclerosis. In order to clarify the mechanism that visceral fat accumulation causes metabolic and cardiovascular diseases, we have analyzed gene expression profile in subcutaneous adipose tissue and visceral adipose tissue. From the analysis, we found that adipose tissue, especially visceral adipose tissue expressed abundantly the genes encoding bioactive substances such as cytokines, growth factors and complements. In addition to known bioactive substances, we found a novel collagen-like protein which we named adiponectin. Adiponectin is present in plasma at a very high concentration and is inversely associated with visceral fat accumulation. Adiponectin has anti-diabetic, anti-hypertensive and anti-atherogenic properties and recent studies revealed that this protein has an anti-inflammatory and anti-oncogenic function. Therefore hypoadiponectinemia induced by visceral fat accumulation should become a strong risk factor for metabolic and cardiovascular diseases and also some kinds of cancers.In this review article, I would like to discuss the mechanism of life style-related diseases by focusing on the dysregulation of adiponectin related to obesity, especially visceral obesity.

Fig. 1

High risk obesity (left) and low risk obesity (right) in classical paintings.

Fig. 2

Marked variation of fat distribution between intra-abdominal cavity and subcutane.

Fig. 3

Visceral fat accumulation is related a variety of diseases.

Fig. 4

Distribution profile of gene groups expressed in visceral fat and subcutaneous fat.

Fig. 5

Concept of adipocytokines.

Fig. 6

Correlation between visceral adiposity and plasma levels of adiponectin and PAI-1.

Fig. 7

Adipose-specific collagen-like protein, adiponectin.

Fig. 8

Adiponectin accumulate injured vascular walls by binding subendothelial collagens.

Fig. 9

Cell biological mechanism of anti-atherogenicity of adiponectin.

Fig. 10

A disease entity of hypoadiponectinemia