Visceral Fat Accumulation and
Cardiovascular Disease
Yilji Matsiizawa, Taclushi Nakamura, Iichiro Shimomura, Kaziiaki Kotani
Abstract
MATSUZAWA, YUJI, TADASHI NAKAMURA,
I I C H I R O S H I M O M U R A AND KAZUAKI
KOTANI. Visceral fat accumulation and cardiovas-
cular diseaqe. Obes Res. 1995;3(Suppl5):645S-647S.
Classification of Obesity. It has been noted that the
incidence of metabolic complications among equally
obese subjects differs depending on their physique
(11) and there has been more scientific assessment in
recent years that complications such as diabetes mel-
litus or hyperlipidemia are related to adipose tissue
distribution (5). In 1983, we reported a method for
adipose tissue analysis using computed tomography
(CT), which enables the analysis of adipose tissue in
the body cavity, e.g., abdominal cavity or thoracic
cavity, as well as subcutaneous fat (10). Using this
method, we found that the patients with accumula-
tion of fat in the abdominal cavity have a higher inci-
dence of complication (1).
Based on this finding, we proposed a classifica-
tion into visceral fat obesity by visceral fat area
(V)/subcutaneous fat area (S) ratios obtained from
CT cross sectional pictures of the umbilical region.
We divided obese subjects a t a VIS ratio of 0.4, clas-
sifying those with a ratio of 0.4 or more as a visceral
fat obesity group and those with VIS ratio of below
0.4 as a subcutaneous fat obesity group. Disorders of
glucose and lipid metabolism were more marked in
the visceral fat obesity than subcutaneous fat obesity
even when sex a n d age were matched. We also
demonstrated that visceral fat obesity is more fre-
quently accompanied by circulatory disorders such
From The Second Department of Internal Medicine, Osaka University Medical
School, Japan.
Reprint requests to Prof. Matsuzawa, The Second Department of Internal
Medicine, Osaka University Medical School, 2-2, Yamadaoka, Suita, Osaka
565, Japan.
Copyright 01995 NAASO.
as left ventricular enlargement (8) and hypertension
than subcutaneous fat obesity (2).
Key words: VIS ratio, visceral fat syndrome, syn-
drome X,deadly quartet, portal FFA
Visceral Fat Accumulation and
Atherosclerosis
Recently, a syndrome with clustering of multiple
risk factors for coronary atherosclerosis has been
focused as proposed by Reven as syndrome X (9) or by
Kaplan as deadly quartet (3). Visceral fat obesity is just
a syndrome with multiple risk factors for atherosclerosis
such as glucose intolerance, hyperlipidemia and hyper-
tension.
We investigated fat distribution in the subjects with
coronary heart disease. Thirty one male patients with
old myocardial infarction or angina pectoris were stud-
ied. Nine out of 31 patients were obese, whose BMI
ranged from 27 to 33. All of them were designated to
be visceral fat obesity. Figure 1 shows three typical CT
images of umbilical level in obese patients with CAD
(Figure 1). Most of the obese patients with CAD pos-
sessed plural risk factors. Analysis of fat distribution in
29 non-obese patients with Cad was also performed and
demonstrated that visceral fat area was increased by
twice compared with that of control subjects, while BMI
and subcutaneous fat area showed no difference. Each
value of subcutaneous fat area and visceral fat area in
non-obese patients with CAD is shown in Figure 2, and
compared with that of control subjects. Table 1 com-
pares metabolic characteristics,blood pressure and num-
ber of risk factors between non-obese CAD patients
with and without increased visceral fat (Table 1). High
VFA group had significantly higher levels of serum
cholesterol and higher tendency of triglyceride levels
and fasting plasma glucose. The subjects with multiple
risk factors are more frequent in non-obese CAD with
OBESITY RESEARCH Vol. 3 Suppl. 5 Dec. 1995 6458
Visceral Fat and Cardiovascular Disease, Matsuzawa et al.
Figure 1: C'T imagcs of three typical obese patients
wih CAD.
high VFA. Figure 3 shows the correlation between vis-
ceral fat area and plasma insulin area after 75 g 0-GTT
in non-obese CAD patients. Plasma insulin area signifi-
cantly correlated to visceral fat area, suggesting that
insulin resistance might be related to visceral fat accu-
mulation even in non-obese subjects with CAD.
Factors Inducing Visceral Fat
Accumulation
Sex hormone might be one of the major factors
determining fat distribution. Vague, a pioneer of obesi-
ty classification by fat distribution, classified obesity
into android type and gynoid type. Although visceral
fat obesity is not identical to android type, visceral fat
accumulation is more predominant in male than female
when compared in age-matched obese subjects with
similar BMI. Aging is also a very important factor to
promote visceral fat accumulation. In male, there was
close lineal correlation between age and visceral fat vol-
ume, suggesting visceral fat increased continuously with
age. Although this correlation was also present in
female subjects, the slope was very gentle in pre-
menopausal subjects. It became steep in post-
400F
-
VFA
p < 0.01
SFA
2004 0
0'
CAD Control CAD Control
Figure 2: Comparison of visceral and subcutaneous fat
areas between non-obese CAD patient and non-obese
control subiects.
6468 OBESITY RESEARCH Vol. 3 Suppl. 5 Dec. 1995
". 100 200 300
0
Visceral Fat Area (cm')
Figure 3: Correlation between visceral fat area and
plasma insulin area in non-obese patients with CAD.
menopausal subjects, which is almost the same as that
of male (6). We also studied fat distribution in Japanese
professional Sumo wrestlers in order to investigate the
effect of physical exercise on fat distribution in obesity.
Sumo wrestlers are very heavy without exception. They
eat a high-energy diet (5000 - 7000 kcal/day) to gain
body weight, but at the same time they are forced to per-
form very hard physical exercise every day. The aver-
age V/S ratio of Sumo wrestlers was 0.25, which is
comparable to subcutaneous fat obesity. Most of them
still maintain normal plasma glucose and triglyceride
and have unexpectedly low cholesterol, even compared
with normal controls. CT scan imaging at the level of
the umbilicus demonstrated fat accumulation only in the
subcutis in most of the Sumo wrestlers, with marked
muscularity (7). These data suggest that physical exer-
cise or development of muscularity may prevent the
accumulation of visceral fat even with a very high ener-
gy intake. As a dietary factor, high sucrose intake is a
candidate to induce visceral fat accumulation. We
reported that high sucrose loading increased mesenteric
I
aging
+ lack of exercise
Visceral Fat Accumulation
( Lipogenesis 4 ) ( Lipolysis 4 )
sucrose diet
Portal FFASS 1
Lipid synthesis 4 .
Insulin resistance
1 Atherosclerosis I
Figure 4: Working hypothesis of pathogenesis and
pathophysiology of visceral fat syndrome.
Visceral Fat and Cardiovascular Disease, Matsuzawa et al.
fat both in ventromedial hypothalamus (VMH)-lesioned
obese rats and sham-operated rats (4).
Link Between Visceral Fat Accumulation
and Metabolic and Circulatory Disorders
In order to clarify the mechanism by which visceral
fat accumulation causes metabolic and circulatory disor-
ders, we investigated the metabolic characteristics of
mesenteric fat which comprises the greatest part of so-
called visceral fat determined by CT scan at the umbili-
cus level. Mesenteric fat was shown to have higher
lipolytic activities when glycerol liberation was stimu-
lated by norepinephrine, a result similar to the one that
occurs in omental fat as reported by Rebuffe-Scrive et
al. We also demonsuated that lipogenic activity is also
more active in mesenteric fat than subcutaneous fat
from the observation of the enhancement of m-RNA of
acyl-CoA synthesis which is one of key enzymes of
lipogenesis. These results indicate that visceral fat is
metabolically very active, releasing free fatty acids into
portal circulation which goes into the liver directly.
Excess free fatty acids may cause the enhancement of
lipid synthesis in the liver and also cause insulin resis-
tance, resulting in hyperlipidemia, glucose intolerance
and hypertension, and finally atherosclerosis (Figure 4).
References
1. FuJioka S , Matsuzawa Y , T o k u n a -
g a K, e t al.
Contribution of intraabdominal fat accumulation to the
impairment of glucose and lipid metabolism.
Metabolism. 1987;36:54-59.
2. Kanai H, Matsuzawa Y,Kotani K, et al. Close correla-
tion of intraabdominal fat accumulation to hypertension
in obese women. Hypertension. 1990;16:484-490.
3. Kaplan NM. The deadly quartet. Arch Intern Med.
1989;143:1514-1520.
4. Keno Y, Matsuzawa Y, Tokunaga K, et al. High
sucrose diet increases visceral fat accumulation in VMH-
lesioned obese rats. Int J Obes. 1992;15:205-211.
5. Kissebah AH, Vydelingum N, M u r r a y R, e t al.
Relation of body fat distribution to metabolic complica-
tion of obesity. J Clin Endocrinol Metab. 1982;54:254-
260.
6. Kotani K, Tokunaga K, Fujioka S, et al. Sexual dimor-
phism of age-related changes in whole-body fat distribu-
tion in the obese. Int J Obes. 1994;18:207-212.
7.Matsuzawa Y , T o k u n a g a K, Fujioka S, e t al.
Pathophysiology of visceral fat obesity. In: Oomura Y,
et al, eds. Progress in Obesity Research. London: John
Libbey & Co. Ltd; 1990:309-312.
8. Nakajima T, Fujioka S, T o k u n a g a K, e t al.
Correlation of intraabdorninal fat accumulation and left
ventricular performance of obesity. Am J Curdiol.
1989;64:369-373.
9. Reaven GM. Role of insulin resistance in human dis-
ease. Diabetes. 1988;37:1595-1607.
10. Tokunaga T, Matsuzawa Y, Ishikawa K, et al. A
novel technique for the determination of body fat by
computed tomography. Int J Obes. 1983;7:437-445.
11. Vague J. La differentation sexuelle-facteur determinant
des formes de l'obesity. Presse Med. 1947;30:339-340.
OBESITY RESEARCH Vol. 3 Suppl. 5 Dec. 1995 647s