Shigenori Fujioka

Contribution of intra-abdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity.

The casual relationship between intraabdominal visceral fat accumulation and metabolic disorders was analyzed in 46 obese subjects (15 males, 31 females) having 34.1 +/- 5.5 of body mass index (BMI). The distribution of fat was determined by our CT scanning technique (Int J Obesity 7:437, 1983). The total cross-cut area, subcutaneous fat area, and intra-abdominal fat area was measured at the umbilical level. The fasting plasma glucose level, area under the plasma glucose concentration curve after oral glucose loading (plasma glucose area), fasting serum triglyceride level, and serum total cholesterol level were all significantly higher or otherwise greater in the group with intraabdominal visceral fat to subcutaneous fat ratio (V/S ratio) of not less than 0.4 than in the group with a lower V/S ratio, when either all or sex-matched obese subjects were examined, though BMI or the duration of obesity was not different between the two groups. The V/S ratio was significantly correlated with the level of plasma glucose area (r = 0.45, P less than .001) under the curve of 75 g oral glucose tolerance test and also with the serum triglyceride (r = 0.65, P less than .001) and total cholesterol levels (r = 0.61, P less than .001). These relationships were also observed when examined in each sex separately and found to be significant after adjustment for BMI and age by multiple regression analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Contribution of visceral fat accumulation to the development of coronary artery disease in non-obese men

Associations between intra-abdominal visceral fat accumulations and coronary risk factors were studied in a sample of 29 non-obese men aged 57 +/- 10 years with coronary artery disease (CAD). Their body mass indexes (BMI) were 23.8 +/- 1.5 (range 18.7-26.3). The visceral fat area (VFA) and the subcutaneous fat area (SFA) were measured at the level of the umbilicus by computed tomography. In patients with CAD, the average VFA was significantly increased compared with that in 54 control subjects without CAD, matched for sex, age, and BMI (117.2 +/- 53.1 vs. 93.8 +/- 38.6 cm2, P < 0.05). However, their average SFA was not statistically different (111.2 +/- 33.3 vs. 106.3 +/- 35.7 cm2, N.S.). Eleven CAD patients (38%) and nine control subjects (17%) had greater than 2 S.D. higher than the mean VFA obtained from 22 healthy subjects extracted from the control subjects. Accordingly, the proportion of the subjects with high VFA was significantly higher in the CAD group. This group also had significantly higher levels of plasma glucose and insulin areas than controls determined by oral glucose tolerance tests. This may be due to insulin resistance. The proportion of the subjects with multiple risk factors including hyperlipidemia, hyperglycemia, and hypertension was significantly higher in the CAD patients with high VFA compared with the control subjects with normal VFA (CAD with high VFA 82% and control with normal VFA 33%). These findings suggest that visceral fat accumulations may play an important role in the occurrence of CAD regardless of obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

Close correlation of intra-abdominal fat accumulation to hypertension in obese women.

The relation between intra-abdominal visceral fat accumulation and blood pressure was investigated in 67 obese women (mean body mass index, 33.6 +/- 3.1; average age, 50 +/- 11 years). As an index of intra-abdominal fat accumulation, the ratio of the intra-abdominal visceral fat area to subcutaneous fat area was determined using a computed tomographic section at the level of the umbilicus. When the obese subjects were divided into a hypertensive group and a normotensive group, the ratio of the intra-abdominal visceral fat area to subcutaneous fat area in the hypertensive group was significantly higher (0.53 +/- 0.33 versus 0.29 +/- 0.12, p less than 0.01). Significant correlations between the ratio of intra-abdominal visceral fat area to subcutaneous fat area and systolic blood pressure (r = 0.62, p less than 0.001) and diastolic blood pressure (r = 0.53, p less than 0.001) also were found. However, no significant difference existed in either the body mass index or the waist-to-hip circumference ratio between the hypertensive and normotensive groups. Plasma renin activity, aldosterone, epinephrine, and norepinephrine levels were not significantly different between the two groups. Moreover, the correlation between the ratio of the intra-abdominal visceral fat area to subcutaneous fat area ratio and blood pressure was found independent of age and body mass index by multiple regression analyses. We conclude that intra-abdominal fat accumulation itself may play an important role in the pathogenesis of hypertension in obesity.

Correlation of intraabdominal fat accumulation and left ventricular performance in obesity.

The correlation of intraabdominal visceral fat accumulation and left ventricular performance was investigated in 37 obese patients who had 154 +/- 23% of ideal body weight. The left ventricle was studied noninvasively by means of echocardiography, whereas the distribution of body fat was determined by computed tomography. The end-diastolic left ventricular dimension and stroke volume were greater in obese patients than in non-obese control subjects. Not only the absolute values of these parameters, but also the diastolic left ventricular dimension index (calculated as end-diastolic dimension/cube root of body surface area) and stroke index were greater in obese patients. When the obese patients were divided into 2 groups according to the intraabdominal visceral fat area to subcutaneous fat area ratio (V/S) determined by computed tomography, the diastolic dimension index and the stroke index were significantly greater in visceral-type obesity (V/S greater than or equal to 0.4) than in subcutaneous-type obesity (V/S less than 0.4) (43.2 +/- 2.9 vs 40.3 +/- 3.1 mm/m2/3, p less than 0.01 and 49.3 +/- 6.1 vs 40.3 +/- 5.6 ml/m2, respectively). Multiple regression analysis with independent variables of age, body weight, duration of obesity and V/S ratio showed that diastolic dimension index and stroke index significantly correlated with the V/S ratio. Thus, the alteration of cardiac function in obese patients is attributable not only to excess body weight and duration of obesity but also to intraabdominal fat accumulation.

Decrease in Intra-Abdominal Visceral Fat May Reduce Blood Pressure in Obese Hypertensive Women

We investigated the relationship between changes in blood pressure and fat distribution after a 12-week low-calorie diet in 26 obese hypertensive women whose average age was 50 +/- 13 years, mean body mass index was 33.7 +/- 3.1 kg/m2, and mean blood pressure was 112 +/- 9 mm Hg. As an index of intra-abdominal fat accumulation, we used the ratio of the intra-abdominal visceral fat area to subcutaneous fat area, determined by a computed tomographic section at the level of the umbilicus. Subjects lost a mean of 9.4 +/- 4.1 kg on a 1200-kcal (5040-kJ) diet for 12 weeks. Their mean blood pressure fell from 112 +/- 9 to 101 +/- 12 mm Hg (P < .001). The ratio of the visceral to subcutaneous fat area was significantly reduced after weight reduction from 0.56 +/- 0.33 to 0.45 +/- 0.27 (P < .02). Fasting plasma glucose and plasma glucose area after a 75-g oral glucose tolerance test also were significantly reduced by weight reduction. The change in mean blood pressure after weight reduction was not correlated with the change in body weight or body mass index but was correlated with the reduction in visceral fat area or ratio of visceral fat to subcutaneous fat area. Changes in mean blood pressure also were correlated with changes in fasting plasma glucose levels and the plasma glucose area determined by 75-g oral glucose tolerance test. Results indicate that a decrease in intra-abdominal visceral fat, rather than simply of body weight, may reduce blood pressure in obese hypertensive subjects. The mechanism may involve an improvement in glucose tolerance caused by weight reduction.

Noninvasive study of left ventricular performance in obese patients: influence of duration of obesity.

We studied the performance of the left ventricle in 35 obese patients by means of noninvasive methods, including echocardiography, carotid arterial pulse tracing, and phonocardiography. Patients were divided into two groups according to the duration of obesity: group 1 included patients who had been obese for less than 15 years, and group 2 comprised patients who had been obese for more than 15 years. There were no differences in the degree of obesity and cellularity of adipose tissue between two groups. Left ventricular dimension and wall thickness, stroke volume, and cardiac output were significantly greater in both groups of obese patients than in nonobese control subjects. Group 2 had a significantly increased end-diastolic dimension index (DdI, calculated as end-diastolic dimension/cube root of body surface area), stroke index (SI), and radius/wall thickness ratio (R/Th) of the left ventricle compared with group 1. Multiple regression analysis showed that DdI, SI, and R/Th correlated significantly with the duration of obesity. We conclude that alterations of cardiac performance in obese patients with left ventricular enlargement and wall thickening is attributed not only to the excess of body weight but also to the duration of obesity.

Classification of Obesity with Respect to Morbidity

Obesity is defined as an excess accumulation of adipose tissue in the body. Since its etiology and pathogenesis are quite heterogenous, classification of disease types by specific purposes is essential for proper clinical management. Although classification by the etiology given in Table I is useful for diagnosing the primary disease inducing obesity, it would be more meaningful to classify simple obesity into subgroups and determine pathological features of each disease type, since simple obesities without specific identifiable cause are much more often encountered in daily medical care. From this viewpoint, classification by morphological types of fat cells or by sites of adipose tissue accumulation has been carried out as shown in Parts II and III of Table I, and features of each disease type have been reviewed. This paper explains the above in detail, and describes a method of classification that incorporates the concept of visceral fats in comparison with conventional methods. As for the accumulation sites, visceral fat can be analyzed by a newly developed method. Classification by Cytological Features of Adipose Tissue This is to classify obesities by cellularity of the adipose tissue biopsied, i.e., by the size and number of fat cells (1). The following classifications are employed because metabolic disorders accompanying obesity are related to the size of fat cells and because of the relationship between the proliferative capacity of fat cells and the onset of obesity. Hyperplastic Type. Fat cells are normal in size, but are increased in number. Fat cells are said to actively proliferate from the embryonal period (the last trimester of pregnancy) to 1 year after birth, and again during puberty. This type is, therefore, often seen among obese people with onset in youth. Since fat cells are not large, metabolic disorders rarely occur. The treatment for weight reduction is not so effective.

PVN-lesioned obese rats maintain ambulatory activity and its circadian rhythm

We investigated physical activity and its circadian rhythm as well as food and water intake in PVN-lesioned rats compared to those of VMH-lesioned rats. Body weight, food and water intake and ambulatory activity were recorded automatically on a microcomputer on the fourth day after creation of the PVN or VMH lesion. The weight gain in the PVN-lesioned rats was almost the same as that of the VMH-lesioned rats. The PVN-lesioned rats maintained the same circadian rhythm of eating and drinking as the controls. The ambulatory activity in the VMH-lesioned rats during the 24-h period was significantly less than the sham-operated rats, but that of the PVN-lesioned rats was almost the same as the sham-operated rats. The dominance of ambulatory activity in the dark period was observed in the PVN-lesioned rats as well as controls, in contrast to the VMH-lesioned rats, in which circadian rhythm was abolished. These results demonstrate that the PVN-lesioned obese rats show clear differences in physiological behavior from the VMH-lesioned rats.

Inhibitory effect of a new α-glucosidase inhibitor on fatty liver in Zucker fatty rats

The livers of Zucker fatty (fa/fa) and lean (Fa/-) rats treated with standard rat chow diet containing 0, 10 or 50 ppm alpha-glucosidase inhibitor (AO-128) for 10 weeks were studied morphologically and biochemically. Light microscopic examination of livers from untreated Zucker fatty rats showed severe steatosis. The triglyceride content in the livers from Zucker fatty rats was significantly higher than that from lean rats (73 +/- 9 micrograms/mg protein for Zucker fatty rats vs. 30 +/- 10 for lean rats, p less than 0.01). Administration of the inhibitor caused a marked decrease in the number and size of lipid droplets in the hepatocytes from Zucker fatty rats and a decrease in the triglyceride content in the liver (73 +/- 9 micrograms/mg protein for untreated, 54 +/- 16 for 10-ppm-treated and 48 +/- 23 for 50-ppm-treated rats, p less than 0.05). This is the first report showing an inhibitory effect of an alpha-glucosidase inhibitor on steatosis in Zucker fatty rats.

Increased level of apolipoprotein B mRNA in the liver of ventromedial hypothalamus lesioned obese rats

The mRNA level of apolipoprotein B (apoB), which is a principal protein component of nascent very low density lipoprotein (VLDL), was determined in parallel with the measurement of acetyl-coenzyme A (Ac-CoA) carboxylase activity in the liver of ventromedial hypothalamus (VMH) lesioned obese rats. Eight weeks after the electrolysis of the bilateral VMH, the level of apoB mRNA in the VMH-lesioned rats was about 1.5-fold higher than that in the sham-operated rats, indicating increased apoB synthesis in the liver of the VMH-lesioned obese rats. The activity of Ac-CoA carboxylase, which is a rate-limiting enzyme for the fatty acid biosynthesis, was about 1.8-fold higher in the VMH-lesioned rats. These observations indicated that VLDL synthesis is increased in the liver of VMH-lesioned obese rats.