Intra-abdominal Visceral Fat Research Articles

Body composition in adolescents: measurements and metabolic aspects

Adolescence is a decisive period in human life in which important body composition changes occur. Increase of total body mass and its relative distribution are mainly related to gender and pubertal development. This review explores the specific measurements that may be used in this age group to assess excess body fat and to define obesity and overweight. Identification of subjects at risk for adiposity requires simple anthropometric cutoffs for the screening of overweight and obesity. In this context, BMI criterion is the most frequently used but, in spite of its high sensitivity and specificity, an important number of adolescents classified as overweight or obese do not have really high adiposity (32.1% of females and 42% of males). Excess total body fat and intra-abdominal visceral fat are related to metabolic abnormalities that increase the risk of cardiovascular diseases. Waist circumference seems to be the best simple anthropometric predictor for the screening of the metabolic syndrome in children and adolescents. Early identification of adolescents at risk for adiposity and its related metabolic complications requires reliable, simple and specific measures of excess body fat for this age group.

Progression of Lipodystrophy (LD) with Continued Thymidine Analogue Usage: Long-Term Follow-Up from a Randomized Clinical Trial (The PIILR Study)

Purpose: During the 24-week PIILR study of protease inhibitor (PI) withdrawal, improved lipids and reduction in intraabdominal visceral fat was seen, however, there was also a loss of subcutaneous limb fat in patients with HIV-lipodystrophy (LD). It was hypothesized that overall improvement in LD may require a longer period of time off PIs. Method: Follow-up of patients randomized to stop or continue PI-based therapy for 24 weeks, in a multicenter study, was continued for up to 120 weeks. Biochemistry and lipid parameters were assessed every 3 months. DEXA and CT scans were performed annually. Limb fat, visceral adipose tissue, and the lipodystrophy case definition score (LCDS) were used as indicators of LD severity. Results: Forty-five male patients with baseline and week 120 body composition data were assessed. There were no significant changes in the limb fat or visceral adipose tissue (VAT) components of LD, with the exception of the LCDS (change from baseline +5.79, p < .001). Control of viral replication was maintained and lipid and glycemic parameters were unchanged over the 120-week follow-up. Linear regression analysis showed on-study usage of stavudine was independently and significantly correlated with both decreased limb fat mass and a higher LCDS. Conclusion: Body composition or metabolic features of LD did not improve over 2 years of observation in patients remaining on predominantly PI-sparing therapy. LD was adversely influenced by continued stavudine use.

Relation of intra-abdominal fat distribution to metabolic disorders in nonobese patients with polycystic ovary syndrome

Objective To investigate the relation between intra-abdominal fat distribution and metabolic disorders in nonobese patients with the polycystic ovary syndrome (PCOS). Design Prospective case–control study. Setting University-based hospital. Patient(s) Thirty nonobese patients with PCOS and 30 lean women with regular menstrual cycles (controls). All participants had a body mass index < 25kg/m 2. Main outcome measure(s) Subcutaneous and intra-abdominal visceral and preperitoneal fat thicknesses were assessed by ultrasonography. Glucose tolerance and insulin sensitivity were evaluated by standard 75-g oral glucose tolerance test and area-under-the-curve analysis. Serum hormones and lipid profile were measured. Result(s) The mean preperitoneal and visceral fat thicknesses were significantly greater in nonobese patients with PCOS. Subcutaneous fat mass was similar between the PCOS and control groups. Nonobese patients with PCOS had glucose intolerance, hyperinsulinemia, and dyslipidemia, manifested by high serum levels of triglyceride, total cholesterol, and high-density lipoprotein (HDL) levels and low serum low-density lipoprotein (LDL) levels. No correlation existed between subcutaneous fat thickness and the metabolic variables in nonobese patients with PCOS. However, serum triglyceride levels correlated with visceral fat and preperitoneal fat thickness. The mean HDL level correlated negatively with visceral fat and preperitoneal fat thickness. The area under the curve for insulin and mean fasting insulin levels correlated positively with visceral fat thickness. In multiple regression analysis, visceral fat thickness contributed significantly to high serum triglyceride and fasting insulin levels. Conclusion(s) Intra-abdominal preperitoneal and visceral fat accumulation may contribute to the development of glucose and lipid metabolism disorders in nonobese patients with PCOS.

Sonographic assessment of changes in thickness of different abdominal fat layers in response to diet in obese women.

We evaluated the potential application of sonography to monitor alterations in abdominal fat thickness in obese women before and after dieting. This study included 40 obese women (mean age, 42.2 +/- 9.4 years; mean body mass index [BMI], 36.0 +/- 5.9 kg/m2) who underwent a 3-month low-calorie diet. Height, weight, waist circumference (WC), and hip circumference (HC) were measured. BMI and waist-to-hip ratio (WHR) were calculated. Abdominal subcutaneous (S) and intra-abdominal preperitoneal (P) fat were measured at their maximum (max) and minimum (min) thickness sites using a 7.5-MHz linear-array probe. Intra-abdominal visceral (V) fat was measured using a 3.5-MHz convex-array probe. Measurements were taken before and after caloric restriction. The mean weight was reduced from 88.6 +/- 17.1 kg to 83.0 +/- 15.9 kg (p < 0.0001). The mean changes in S(min) (r = 0.376, p = 0.017), S(max) (r = 0.508, (p = 0.001), P(min) (r = 0.439, p = 0.005), and V (r = 0.365, p = 0.022) fat thicknesses were positively correlated with change in weight; the change in P(max) fat thickness showed the best and most significant correlation (r = 0.591, p < 0.0001). BMI (r = 0.969, p < 0.0001), WC (r = 0.510, p = 0.001), and HC (r = 0.422, p = 0.007) changes were also positively correlated with weight change, but the WHR change (r = 0.019, p > 0.05) was not. All the abdominal fat layers, particularly the intra-abdominal P fat, will decrease in response to loss of body fat by dieting. Sonography seems to be useful in monitoring small variations in the thicknesses of abdominal S and intra-abdominal P and V fat.

Clinical features of a young Japanese woman having marked obesity and abrupt onset of diabetes mellitus with ketoacidosis

The subject was a 26-year-old Japanese woman of 148 cm height, 96.2 kg of body weight (BW) (body mass index (BMI) of 43.8 kg/m 2). She was referred to our hospital on May 1, 2000 for the evaluation of marked hyperglycemia with clinical symptom of general malaise, polydipsia, and ketonuria (3+). She did not smoke, or drink alcohol. But, she tended to eat lots of sweet food every day before the onset of this symptom. Her father was diagnosed type 2 diabetes mellitus. Her fasting plasma glucose and HbA 1c, and serum C-peptide were 398 mg/dl, 7.8% and less than 0.05 ng/ml [normal range: 0.94–2.8], respectively. She tested negative for anti-glutamic acid decarboxylase (GAD) antibodies and islet-cell antibodies. C-peptide level in her urine was as low as 3.4 μg/day. We immediately started insulin treatment under the diagnosis of abrupt onset of diabetes mellitus with diabetic ketoacidosis on the day of her admission, and the insulin treatment was continued after her being discharged. She showed continuous BW reduction until her BW reached approximately 60 kg, followed by her BW being plateau. During the period, intra-abdominal visceral fat (VF) and subcutaneous fat (SF) volume assessed by helical computerized tomography (CT) showed a substantial reduction [3.9–0.5 l for VF, 19–3.2 l for SF volume]. Pre-heparin plasma lipoprotein lipase (LPL) mass showed a considerably lower value when she had continuous BW reduction than did it when her BW reduction discontinued. These findings suggest that in this subject, continuous BW reduction after the abrupt onset of diabetes is closely associated with intra-abdominal fat mass reduction, which may be related to decreased production of LPL.

A novel method of measuring intra-abdominal fat volume using helical computed tomography.

:We present a novel method of scanning for intra-abdominal fat volume by helical computed tomography (CT), and describe the clinical significance of measuring the volumes of intra-abdominal visceral fat (V(vol)) and subcutaneous fat (S(vol)) vs these respective areas determined by conventional slice-by-slice CT at the umbilical level. Subjects with obesity or hyperlipidemia (79 men, 74 women) were recruited for this study. We obtained helical CT scans with a tube current of 150 mA, voltage of 120 kV and 2:1 pitch (table speed in relation to slice thickness), starting at the upper edge of the liver and continuing until the pelvis. The intra-abdominal visceral fat volume was measured by drawing a line within the muscle wall surrounding the abdominal cavity. The abdominal subcutaneous fat volume was calculated by subtracting the visceral fat volume from the total abdominal fat volume. By comparison, the intra-abdominal visceral and subcutaneous fat areas were determined at the umbilical level by the established slice-by-slice CT scanning technique. V(vol) was correlated positively with visceral fat area (V(area)) measured by conventional CT in both genders (in men (n=79) V(vol) vs V(area), r=0.81 P<0.0001; in women (n=74) V(vol) vs V(area), r=0.85, P<0.0001). S(vol) also showed a positive correlation with subcutaneous fat area (S(area)) in both genders (in men (n=78) S(vol) vs S(area), r=0.95, P<0.0001; in women (n=74) S(vol) vs S(area), r=0.92, P<0.0001). We have reported a novel method for measuring intra-abdominal fat volume by the use of helical CT.

Molecular mechanism of vascular disease in metabolic syndrome X

Syndrome X is a clinical syndrome in which multiple risks are clustered in an individual and is a common basis of vascular disease in the industrial countries. However, the molecular basis of syndrome X has not been elucidated. We have analyzed body fat distribution using CT scanning and have shown that accumulated intra-abdominal visceral fat is frequently accompanied by multiple risks and vascular diseases. Thus, ‘‘visceral obesity’’ is a clinical entity compatible with syndrome X. Our studies demonstrated that the V/S ratio (visceral fat area, V/subcutaneous fat area, S) significantly correlated with the glucose area after oral glucose tolerance test (OGTT) and the plasma triglyceride or cholesterol level in obese subjects. Visceral fat accumulation is associated with not only quantitative change in serum lipid and lipoprotein but also qualitative changes in lipoproteins such as the appearance of small, dense LDL particles, which may be related to the high triglyceride–low HDL dyslipidemic state found in visceral fat obesity. Many people believe that insulin resistance or the hyperinsulinemic state that is often found in visceral fat obesity plays a key role in the development of metabolic disorders. Previous reports have shown that hyperinsulinemia, although not so predominant in Japanese subjects, is present in visceral type obesity. Studies using the glucose clamp technique by Kissebah et al. and our steady-state plasma glucose method clearly demonstrated that patients with visceral fat obesity have greater insulin resistance than those with subcutaneous fat obesity. Visceral fat accumulation has been shown to have causative effects in circulatory disorders in addition to metabolic disorders. We demonstrated a close correlation between the V/S ratio and the diastolic dimension index or stroke index in obese subjects that reflected the presence of a hypervolemic state in visceral fat obesity. There was a close correlation between systolic blood pressure and V/S ratio in premenopausal female subjects. As stated above, visceral fat obesity is characterized by high-risk obesity with multiple complications including insulin resistance, disorders of glucose and lipid metabolism, hypertension, and cardiac enlargement. We also demonstrated that the accumulation of visceral fat was related to the development of both metabolic disorders and circulatory disorders even in normal-weight subjects. Thus, a disease entity, ‘‘visceral fat syndrome,’’ can be proposed as a state that is accompanied frequently by glucose intolerance, hyperlipidemia, and hypertension irrespective of absolute body weight. Furthermore, several studies have shown that visceral adiposity determined by CT scanning is related to coronary artery disease (CAD). For example, according to our study on the fat distribution of 38 male patients with CAD, 9 cases were classified as obese with a BMI greater than 26.5 and 29 cases as non-obese. Eight of those nine obese subjects had extremely high V/S ratios compared with those of obese subjects without CAD. Among the non-obese subjects, the mean visceral fat area (VFA) in the patients with CAD was significantly larger than that of non-CAD controls. Thirtyeight percent of non-obese CAD subjects had VFAs greater than the mean ± 2 S.D. of the values obtained in non-CAD controls. The patients with high VFAs showed significantly higher levels of plasma glucose and insulin area after glucose ingestion than those with low VFAs, suggesting the presence of insulin resistance (Matsuzawa, 1997). The incidence of multiple risk factors including hyperlipidemia, hyperglycemia, and hypertension was higher in patients with high VFAs. These results together with previous reports indicate that visceral fat syndrome is a syndrome predisposing to susceptibility to atherosclerosis in which visceral fat accumulation often accompanies insulin resistance, glucose intolerance, hyperlipidemia, and hypertension, and the clustering of these risk factors may result in the occurrence of atherosclerosis. To clarify the molecular mechanism of the disorders in visceral fat syndrome, we analyzed the expressed genes in adipose tissue by large scale random sequencing. Unexpectedly, adipocytes, especially visceral adipocytes expressed a variety of the genes for secretory proteins including various bioactive substances and we designated

Similar PAI-1 Expression in Visceral and Subcutaneous Fat of Postmenopausal Women

Recent studies showed that intraabdominal visceral fat located in the mesenterium and omentum may significantly influence the circulating plasminogen activator inhibitor type 1 (PAI-1). To substantiate this link, we performed analysis of PAI-1 expression in human visceral and subcutaneous adipose tissues in peri- and postmenopausal women. The samples of both visceral and subcutaneous fat from 28 generally healthy women (aged 45–69 years) with a wide range of body mass index (BMI; 22.30–38.67 kg/m 2), who underwent surgical operation due to benign ovary and uterine tumours, were obtained. In these samples, expression of mRNAs for PAI-1, tumour necrosis factor α (TNFα), acyl-CoA synthetase (ACS), and glucose transporter (GLUT-4) was analysed by relative quantitative RT PCR and correlated with plasma PAI-1 antigen. In addition, visceral fat area was measured with computer tomography. Both types of fat tissues contained similar quantities of PAI-1 mRNA, and there was no correlation between plasma PAI-1, measured both by antigen and activity, with either visceral or subcutaneous fat PAI-1 mRNA. Furthermore, there was no significant association between the expression of PAI-1 mRNA and TNFα mRNA in tested fat samples. PAI-1 mRNA in both fat tissues was significantly correlated with plasma levels of estradiol (positive correlation) and follicle-stimulating hormone (FSH; negative correlation). Finally, the expression of PAI-1 mRNA was negatively correlated with mRNA of ACS present in both fat tissues. In summary, this study directly indicates that PAI-1 mRNA is similarly expressed in both subcutaneous and visceral fat of peri- and postmenopausal women and its expression strongly depends upon lipid metabolism.

Effect of apolipoprotein E3/4 phenotype on postprandial triglycerides and retinyl palmitate metabolism in plasma from hyperlipidemic subjects in Japan

In a previous study it was shown that postprandial lipid metabolism is delayed in individuals with intra-abdominal visceral fat accumulation. Population studies have shown that as compared with individuals with apolipoprotein (apo) E3/3, those with phenotype apo E3/4 phenotype have higher plasma and low density lipoprotein (LDL)-cholesterol (C) concentration and increased susceptibility to coronary heart disease. The aim of the present study is to determine how apo E4 affects postprandial lipid metabolism by comparing individuals with apo E3/4 to those with apo E3/3 phenotype matched for abdominal visceral fat. Sixty-two Japanese subjects (41 male, 21 female) [average age 48±14 years; mean body mass index (BMI) 25±5.6 kg/m 2] were recruited for this study. The subjects were divided into two groups: those with apo E3/3 ( n=43) and those with apo E3/4 phenotype ( n=19), as determined by isoelectric focusing (IEF). Visceral fat accumulation was analyzed as area of fat deposition by computerized tomography at the umbilicus level. After a 12-h overnight fasting, an oral vitamin A and a fatty meal were administered to these subjects. The plasma triglyceride (TG) increased significantly hours after fat loading in both groups but the levels of TG were significantly higher in apo E3/4 than in apo E3/3 phenotype at 2, 4 and 6 h after fat loading. Plasma retinyl palmitate (RP) levels were also significantly higher in individuals with apo E3/4 than in those with apo E3/3 phenotype at 2, 4 and 6 h after fat loading. This investigation was then conducted in both genders separately, and found that these associations were statistically significant in men. Furthermore, after matching men for fasting TG levels, these associations did not persist for plasma TG levels at any time point, while plasma RP levels were still significantly higher in apo E3/4 group at 2 and 6 h after fat loading. These results indicate that in Japanese population especially for men apo E phenotype E3/4 is associated with an impaired postprandial TG-rich lipoprotein metabolism relative to apo E3/3 phenotype when matched for intra-abdominal visceral fat accumulation, which has a substantial effect on the metabolism of plasma TG-rich lipoproteins.

Daily melatonin administration to middle-aged male rats suppresses body weight, intraabdominal adiposity, and plasma leptin and insulin independent of food intake and total body fat.

Pineal melatonin secretion declines with aging, whereas visceral fat, plasma insulin, and plasma leptin tend to increase. We have previously demonstrated that daily melatonin administration at middle age suppressed male rat intraabdominal visceral fat, plasma leptin, and plasma insulin to youthful levels; the current study was designed to begin investigating mechanisms that mediate these responses. Melatonin (0.4 microg/ml) or vehicle was administered in the drinking water of 10-month-old male Sprague Dawley rats (18/treatment) for 12 weeks. Half (9/treatment) were then killed, and the other half were submitted to cross-over treatment for an additional 12 weeks. Twelve weeks of melatonin treatment decreased (P<0.05) body weight (BW; by 7% relative to controls), relative intraabdominal adiposity (by 16%), plasma leptin (by 33%), and plasma insulin (by 25%) while increasing (P<0.05) locomotor activity (by 19%), core body temperature (by 0.5 C), and morning plasma corticosterone (by 154%), restoring each of these parameters toward more youthful levels. Food intake and total body fat were not changed by melatonin treatment. Melatonin-treated rats that were then crossed over to control treatment for a further 12 weeks gained BW, whereas control rats that were crossed to melatonin treatment lost BW, but food intake did not change in either group. Feed efficiency (grams of BW change per g cumulative food intake), a measure of metabolic function, was negative in melatonin-treated rats and positive in control rats before cross-over (P<0.001); this relationship was reversed after cross-over (P<0.001). Thus, melatonin treatment in middle age decreased BW, intraabdominal adiposity, plasma insulin, and plasma leptin, without altering food intake or total adiposity. These results suggest that the decrease in endogenous melatonin with aging may alter metabolism and physical activity, resulting in increased BW, visceral adiposity, and associated detrimental metabolic consequences.

Molecular mechanism of metabolic syndrome X: contribution of adipocytokines adipocyte-derived bioactive substances.

Syndrome X is a clinical syndrome in which multiple risks cluster in an individual, and it is a common basis of vascular disease in the industrial countries. The molecular basis of Syndrome X, however, has not been elucidated. We have analyzed body fat distribution using CT scan and have shown that people who have accumulated intra-abdominal visceral fat frequently have multiple risks and vascular diseases. Thus, "visceral fat syndrome" is a clinical entity compatible with Syndrome X. To clarify the molecular mechanism of the disorders in visceral fat syndrome, we analyzed the expressed genes in adipose tissue by a large-scale random sequencing. Unexpectedly, visceral fat expressed a variety of the genes for secretory proteins including various bioactive substances; we designated them adipocytokines. One of them, plasminogen activator inhibitor-1, was overproduced in accumulated visceral fat and might contribute to the development of vascular disease. We have also cloned a novel adipose-specific gene named adiponectin. Adiponectin is a collagen-like plasma protein which has an inhibitory effect on proliferation of vascular smooth muscle cells; its plasma levels are paradoxically decreased in obesity. Adipocytokines may play important roles in the development of the disorders in Syndrome X.

Changes in Intra-Abdominal Visceral Fat and Serum Leptin Levels in Patients With Obstructive Sleep Apnea Syndrome Following Nasal Continuous Positive Airway Pressure Therapy

Obstructive sleep apnea syndrome (OSAS) is a common disorder in obese subjects. Visceral fat accumulation (VFA) is a better predictor of coronary heart disease than body mass index. Leptin is a hormone involved in the control of body weight and fat distribution. The effect of nasal continuous positive airway pressure (NCPAP) treatment on VFA and serum leptin levels in OSAS patients has not been known. VFA and subcutaneous fat accumulation (SFA) were assessed by CT before and after NCPAP treatment in 22 OSAS patients (mean apnea and hypopnea index >50 episodes/h). Serum leptin levels of another 21 OSAS patients were measured before and after 3 to 4 days of NCPAP to gain insight into the mechanism by which NCPAP affects fat distribution. VFA and SFA decreased significantly after 6 months of NCPAP treatment (236+/-16 to 182+/-14cm(2), P=0.0003 and 215+/-21 to 189+/-18 cm(2), P=0.003, respectively). VFA decreased significantly in the body weight reduction group (n=9, P<0.01) and the no body weight reduction group (n=13, P<0.03). In contrast, SFA changed significantly in the body weight reduction group only (P<0.01). Leptin levels decreased significantly following 3 to 4 days of NCPAP (P<0.01), whereas body weight, fasting insulin, and cortisol levels did not change significantly. Correction of sleep disordered breathing by NCPAP may be used to reduce VFA in OSAS patients. OSAS may have significant effects on the serum leptin levels.

Delayed post‐prandial lipid metabolism in subjects with intra‐abdominal visceral fat accumulation

Individuals with obesity, in particular those with intra-abdominal visceral fat accumulation, are known to have various complications, such as hyperlipidaemia, impaired glucose tolerance, hyperinsulinaemia and hypertension, leading to the development of coronary heart disease. Post-prandial hyperlipidaemia has repeatedly been shown to be an independent risk factor for coronary heart disease. The aim of the present study was to investigate post-prandial lipoprotein metabolism in subjects with excessive visceral fat accumulation. Eighty-three patients (52 men, 31 women) [average age 48 +/- 14 years; mean body mass index (BMI) 25 +/- 5 kg m-2] were recruited to the study. Visceral (or subcutaneous) fat accumulation was analysed as areas of fat deposition by computerized tomography at the umbilicus level. After a 12-h overnight fast, oral vitamin A and a fatty meal (40 g m-2 fresh cream containing 50 000 units m-2 vitamin A) were administered to these subjects. The concentration of retinyl palmitate (RP) was measured by high-performance liquid chromatography. The visceral fat area (V) was positively correlated with plasma triglyceride (TG) 0, 2, 4 and 6 h after fat loading and with plasma RP 0, 4 and 6 h after fat loading. The BMI did not show any correlation with plasma TG and RP at any point. The visceral fat area was positively correlated with the RP area under the curve (AUC) in the serum from the subjects [V vs. RP AUC: n = 83, r = 0.327, P = 0.013]. The BMI of the subjects did not show any correlation with the RP AUC (r = 0.021, P = 0.85). These results suggest that post-prandial lipid metabolism is impaired in subjects with intra-abdominal visceral fat accumulation, irrespective of BMI, leading to the development and progression of coronary atherosclerosis.

The impairment of flow-mediated vasodilatation in obese men with visceral fat accumulation.

Obesity has been reported to be associated with coronary artery disease and other atherosclerotic diseases. Recently, evidence has accumulated indicating that intra-abdominal visceral fat accumulation contributes to atherogenesis; however, the mechanism underlying this remains to be determined. This study was undertaken to elucidate whether intra-abdominal visceral fat accumulation impairs vascular endothelial function in obese men. Thirty-eight obese men (body mass index (BMI) > or = 26.0), aged 19-64 y (mean age 37.6 +/- 1.8 y) and 23 age-matched non-obese subjects were examined. According to the ratio of the maximum thickness of preperitoneal fat to the minimum thickness of subcutaneous fat (Pmax/Smin) obtained by longitudinal ultrasound scanning in the subxiphoid region in obese men, we divided obese subjects into two categories; visceral (Pmax/Smin > or = 1; n=23) and subcutaneous type (Pmax/Smin < 1; n=15). To investigate endothelial function, we performed ultrasound measurement of the brachial artery diameter non-invasively both at rest and during reactive hyperaemia in the muscle distal to the brachial artery which causes endothelium-dependent vasodilatation. The brachial diameter change was also measured after sublingual administration of nitroglycerin, which causes endothelium-independent vasodilatation. Flow-mediated diameter (D) increase (%FMD; deltaD/D x 100), in the subjects with visceral type obesity (3.09 +/- 0.43%) was significantly lower than those of the subjects with subcutaneous type obesity and non-obese subjects (7.90 +/- 0.51%, 8.91 +/- 0.44%, respectively, P < 0.01). The magnitude of endothelium-independent vasodilatation by nitroglycerin was similar in all groups. On multiple regression analysis, the Pmax/Smin showed a significant inverse correlation with %FMD. The subjects with visceral type obesity, rather than those with the subcutaneous type, are associated with impaired flow-mediated endothelium-dependent vasodilatation of the brachial artery.

Lipoprotein lipase mass and activity in post-heparin plasma from subjects with intra-abdominal visceral fat accumulation.

The purpose of this study was to investigate the possibility of impaired lipolysis of triglyceride-rich lipoproteins in patients with abdominal visceral fat accumulation by assessing two major lipolytic enzymes in the plasma, lipoprotein lipase (LPL) and hepatic lipase (HL). A total of 31 patients [20 men, 11 women, age 50 +/- 7 years old, body mass index (BMI) 26 +/- 2 kg/m2 (mean +/- sd)] were analyzed. Visceral fat and subcutaneous fat areas were evaluated using a computerized tomographic (CT) method at the level of the umbilicus. Total lipolytic activity in the postheparin plasma (PHP) was measured using Triton X-100-emulsified triolein and LPL activity was calculated as the activity in whole plasma inhibited by the 5D2 monoclonal antibody for LPL. LPL enzyme mass was determined by a sandwich enzyme immunoassay. The visceral fat area was found to be negatively correlated with LPL mass (V vs LPL mass, r = -0.37, P = 0.04) in PHP and had a tendency toward negative correlation with the LPL activity in the PHP (V vs LPL activity, r = -0.29, P = 0.12). Subcutaneous fat area, on the other hand, did not show any correlation with LPL activity (r = 0.13, P = 0.49) or mass (r = 0.22, P = 0.25) in the PHP. The visceral fat area was found to be positively correlated with fasting serum insulin levels (r = 0.67, P < 0.01). Body mass index (BMI) was not correlated with LPL mass or activity in the PHP. Multi-regressional analysis showed that abdominal visceral fat could be correlated with LPL mass in the PHP, independently of fasting serum insulin. The HL activity from PHP of the patients did not show significant correlation with visceral fat area, subcutaneous fat area or body mass index. Fat distribution affects LPL mass and activity, either directly or via another metabolic abnormality such as insulin resistance, leading to impaired hydrolysis of triglycerides in chylomicrons and very low density lipoproteins (VLDL) in these subjects.

Measurement of Abdominal Fat by Magnetic Resonance Imaging of OLETF Rats, an Animal Model of NIDDM

We measured abdominal fat masses (intra-abdominal visceral fat summing retroperitoneal, mesenteric, and epididymal fat and subcutaneous fat) and analyzed abdominal fat distribution of Otsuka Long-Evans Tokushima Fatty (OLETF) rats with non-insulin-dependent diabetes mellitus and control strain Long-Evans Tokushima Otsuka (LETO) rats using magnetic resonance imaging. Intra-abdominal visceral and subcutaneous fat were highly correlated with body weight both in OLETF and in LETO rats. Both intra-abdominal visceral and subcutaneous fat of OLETF rats significantly accumulated compared with those of LETO rats. Intra-abdominal visceral fat mass correlated positively with subcutaneous fat mass, and the accumulation of intra-abdominal visceral fat mass was about 3.5 times that of subcutaneous fat. Thus, obesity of OLETF rats was characterized by marked accumulation of intra-abdominal visceral fat compared with that of subcutaneous fat. Body weight and abdominal fat of OLETF rats were closely correlated with the level of total plasma glucose measured by oral glucose tolerance test. However the ratio of intra-abdominal visceral to subcutaneous fat of OLETF rats was not correlated with the level of total plasma glucose.

Close correlation between visceral fat accumulation and uric acid metabolism in healthy men

We evaluated the effect of accumulation of intraabdominal visceral fat on the metabolism of uric acid in 50 healthy male subjects to elucidate any relationship between such obesity and hyperuricemia. The area of abdominal fat (visceral fat and subcutaneous fat) was measured at the level of the umbilicus by abdominal computed tomographic scanning. Serum and urinary concentrations of uric acid and creatinine were determined with an autoanalyzer. Uric acid clearance and the ratio of urinary uric acid to creatinine excreted in urine were calculated. Univariate and multivariate analyses were used to evaluate the relationship between uric acid metabolism and body fat. The size of the area of visceral fat was significantly correlated with the serum concentration of uric acid ( r = .37, P < .01), uric acid clearance ( r= −.34, P < .05), and the urinary uric acid to creatinine ratio ( r = .65, P < .0001). The size of the area of subcutaneous fat was significantly correlated only with the urinary uric acid to creatinine ratio ( r = .38, P < .01). Multivariate analyses, including body mass index (BMI), showed that the size of the visceral fat area was the strongest contributor to an elevated serum concentration of uric acid, a decrease in uric acid clearance, and an increase in the urinary uric acid to creatinine ratio. These results suggest that accumulation of visceral fat may have a greater adverse effect on the metabolism of uric acid than BMI or accumulation of subcutaneous fat. Clearly, patients with hyperuricemia should lose weight to reduce excessive visceral fat stores, to help avoid attacks of gout.

The effects of weight loss treatments on upper and lower body fat.

The intra-abdominal visceral deposition of adipose tissue, which characterises upper body obesity, is a major contributor to the development of hypertension, glucose intolerance and hyperlipidaemia. Conversely, individuals with lower body obesity may have comparable amounts of adipose tissue but remain relatively free from the metabolic consequences of obesity. This raises an obvious question-are there particular weight reducing treatments which specifically target intra-abdominal fat? In theory, surgical removal of upper body fat should be effective. In reality, neither liposuction nor apronectomy ('tummy tuck') have any beneficial metabolic effects, they simply remove subcutaneous adipose tissue which is often rapidly replaced. Vertical banded gastroplasty and gastric bypass operations may be dramatically effective in improving blood pressure, insulin sensitivity and glucose tolerance. However, these benefits result from a parallel reduction in visceral and total body fat. Studies of body fat distribution in postmenopausal women confirm that the marked decrease in adiposity, following a programme of very low calorie diet and exercise, reflects a comparable reduction in visceral and thigh fat. The reduction in waist circumference after a low fat/exercise programme suggests a similar situation in men. Exercise has an important role in treatment but, once again, the fat loss is generalised. Nevertheless, the improved metabolic parameters seen in exercising obese subjects, independent of weight loss, suggest other beneficial actions. Growth hormone (GH) has a marked lipolytic action. GH replacement treatment for GH deficient adults with pronounced abdominal fat deposition, has been shown to reduce intra-abdominal fat by 47% compared to 27% decrease in abdominal subcutaneous fat. Similar beneficial actions on abdominal fat have been reported following treatment with testosterone in obese men. The potential hazards of such treatments make them unsuitable therapy for obesity. Dexfenfluramine is effective in reducing total body fat but the results from a six month randomised controlled trial indicates that it does not specifically influence changes in waist circumference associated with weight loss. In conclusion, any treatment which reduces total body fat will, by its nature, reduce intra-abdominal visceral fat. There are presently no specific treatments which can be recommended for intra-abdominal fat but increasing knowledge of the biochemical aberrations associated with visceral adiposity may lead to more specific therapies for the future.

Long-term testosterone administration increases visceral fat in female to male transsexuals.

The amount of intraabdominal (visceral) fat is an important determinant of disturbances in lipid and glucose metabolism. Cross-sectional studies in women have found associations between high androgen levels and visceral fat accumulation. The causal relation between these phenomena is unknown. We, therefore, studied prospectively the effect of testosterone administration on body fat distribution in 10 young, nonobese, female to male transsexuals undergoing sex reassignment. Before, after 1 yr, and after 3 yr of testosterone administration, magnetic resonance images were obtained at the level of the abdomen, hip, and thigh to quantify both sc and visceral fat depots. After 1 yr of testosterone administration, sc fat depots at all levels showed significant reductions compared to baseline measurements. The mean visceral fat area did not change significantly, but subjects who gained weight in the first year after testosterone administration showed an increase in visceral fat. After 3 yr of testosterone administration, sc fat depots were no longer significantly lower compared to pretreatment measurements, but the mean visceral fat depot had increased significantly by 13 cm2 (95% confidence interval, 4-22 cm2), a relative increase of 47% (95% confidence interval, 8-91%) from baseline. The increase in visceral fat was most pronounced in those subjects who had gained weight. We conclude that long term testosterone administration in young, nonobese, female subjects increases the amount of visceral fat. In addition, an increase in weight in this hyperandrogenic state leads to a preferential storage of fat in the visceral depot.

Importance of intra-abdominal visceral fat accumulation to coronary atherosclerosis in heterozygous familial hypercholesterolaemia.

Hyper-low-density lipoprotein (LDL)-cholesterolaemia is a potent risk factor for coronary atherosclerosis. We have recently demonstrated that a cluster of risk factors including insulin resistance, glucose intolerance, hypertriglyceridaemia, and hypertension based on intra-abdominal visceral fat accumulation are closely related to coronary artery disease. In the current study, we evaluated the relationship between visceral fat accumulation and the severity and distribution of coronary atherosclerosis in familial hypercholesterolaemia (FH). The effect of visceral fat accumulation on coronary lesions and risk factors in patients with FH was investigated. Thirty-one male patients with heterozygous FH who underwent coronary angiography. Abdominal fat distribution was estimated by a cross-sectional computed tomographic scan at the umbilical level. Plasma lipid, glucose and insulin concentrations and blood pressure were measured. A 75 g oral glucose tolerance test was also performed. The patients were divided into two groups according to the degree of visceral fat accumulation. Fifteen patients had high visceral fat accumulation (High VF group) and 16 patients had normal visceral fat accumulation (Normal VF group). Body mass index (BMI) and subcutaneous fat area were significantly higher in the high VF group. Baseline serum triglyceride was significantly higher and baseline low-density lipoprotein (LDL)-cholesterol and reduction of LDL-cholesterol during treatment were significantly lower in High VF group. Fasting plasma glucose and insulin concentrations, and systolic and diastolic pressures were significantly higher in the High VF group. Significant correlations were found between visceral fat area and the sum of the glucose and insulin concentration during an oral glucose tolerance test. Visceral fat area was significantly correlated with the severity of coronary stenosis index. Distal coronary lesions were significantly more frequent in the High VF group. Moreover, the correlation between the visceral fat area and coronary stenosis index was found to be independent of age, BMI, and subcutaneous fat area by multiple regression analysis. Visceral fat accumulation is a potent cardiovascular risk factor in heterozygous FH.