Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat

Whether visceral adipose tissue has a uniquely powerful association with insulin resistance or whether subcutaneous abdominal fat shares this link has generated controversy in the area of body composition and insulin sensitivity. An additional issue is the potential role of fat deposition within skeletal muscle and the relationship with insulin resistance. To address these matters, the current study was undertaken to measure body composition, aerobic fitness, and insulin sensitivity within a cohort of sedentary healthy men (n = 26) and women (n = 28). The subjects, who ranged from lean to obese (BMI 19.6-41.0 kg/m2), underwent dual energy X-ray absorptiometry (DEXA) to measure fat-free mass (FFM) and fat mass (FM), computed tomography to measure cross-sectional abdominal subcutaneous and visceral adipose tissue, and computed tomography (CT) of mid-thigh to measure muscle cross-sectional area, muscle attenuation, and subcutaneous fat. Insulin sensitivity was measured using the glucose clamp technique (40 mU.m-2.min-1), in conjunction with [3-3H]glucose isotope dilution. Maximal aerobic power (VO2max) was determined using an incremental cycling test. Insulin-stimulated glucose disposal (Rd) ranged from 3.03 to 16.83 mg.min-1.kg-1 FFM. Rd was negatively correlated with FM (r = -0.58), visceral fat (r = -0.52), subcutaneous abdominal fat (r = -0.61), and thigh fat (r = -0.38) and positively correlated with muscle attenuation (r = 0.48) and VO2max (r = 0.26, P < 0.05). In addition to manifesting the strongest simple correlation with insulin sensitivity, in stepwise multiple regression, subcutaneous abdominal fat retained significance after adjusting for visceral fat, while the converse was not found. Muscle attenuation contributed independent significance to multiple regression models of body composition and insulin sensitivity, and in analysis of obese subjects, muscle attenuation was the strongest single correlate of insulin resistance. In summary, as a component of central adiposity, subcutaneous abdominal fat has as strong an association with insulin resistance as visceral fat, and altered muscle composition, suggestive of increased fat content, is an important independent marker of insulin resistance in obesity.     

Surgical removal of visceral fat reverses hepatic insulin resistance

Various cytokines and growth factors may be involved in IgA nephropathy. To clarify whether interleukin-6 was a prognostic factor for this disease, we investigated interleukin-6 positivity of renal biopsy specimens and its relationship with the prognosis. The subjects were 90 patients with IgA nephropathy (42 males and 48 females with a median age of 32.7 +/- 13.8 years). Renal biopsy specimens were stained for interleukin-6 using an enzyme-antibody method. Fifty-two of 90 patients showed glomerular positivity for interleukin-6. Among the patients positive for interleukin-6, 24-hour urinary protein excretion and serum creatinine levels were significantly higher at the time of biopsy than in the patients without interleukin-6 positivity, while creatinine clearance was significantly lower. In the interleukin-6-positive patients without steroid therapy, serum creatinine increased significantly after 1 year (Deltas-Cr; 1.04 +/- 0.45 mg/dl) and creatinine clearance decreased significantly (DeltaCcr; -11.7 +/- 3.2 ml/min) compared to the interleukin-6-negative patients without steroid therapy. Steroid therapy improved 24-hour urinary protein excretion, serum creatinine, and creatinine clearance in the interleukin-6-positive patients, while these parameters worsened without steroid therapy. On the other hand, the IL-6-negative patients showed no differences of clinical parameters irrespective of the presence or absence of steroid therapy. In conclusion, glomerular interleukin-6 positivity may be a prognostic factor and an indicator of the need for steroid therapy in IgA nephropathy.     

Sagittal abdominal diameter as a practical predictor of visceral fat

OBJECTIVE: To evaluate the relationships between the supine sagittal abdominal diameter (SAD) and visceral fat, as well as to evaluate intra- and inter-observer reliability of sagittal diameter measurement. PATIENTS: Twenty-eight women ranging in age from 27-78 y with a body mass index (BMI) ranging from 16.9-48.1 kg/m2 and 23 men ranging in age from 32-75 y with BMI ranging from 20-41.6 kg/m2. MEASUREMENT: Body fat distribution was measured by waist circumference, waist to hip ratio (WHR), SAD, anthropometrically assessed and a single slice of computed tomography (CT) at the L4-L5 level. RESULTS: In both genders, a significant association was found between visceral adipose tissue (AT) and SAD, as evaluated by CT (women r = 0.80; men r = 0.83, P < 0.001), and SAD by anthropometry (women r = 0.76; men r = 0.82, P < 0.001), as well as between visceral AT and waist circumference (women r = 0.76, men r = 0.86, P < 0.001) and WHR (women r = 0.57, P < 0.01, men r = 0.80, P < 0.001). A significant association was also found between subcutaneous AT and SAD by anthropometry (women r = 0.79, men r = 0.74, P < 0.001). After adjusting for BMI, the association between subcutaneous AT and SAD was no longer significant in men and only moderately significant in women (r = 0.42, P < 0.05), while the association between visceral AT and SAD by anthropometry remained significant in both genders (women r = 0.63, P < 0.001; men r = 0.66, P < 0.001). When the subjects were divided into two groups according to BMI (lean to moderately overweight women with BMI < 28 and men with BMI < 30 and obese women with BMI > 28 and men with BMI > 30) we found that the relationships between SAD by anthropometry, as well as SAD by CT and visceral AT, were higher in lean to moderately overweight subjects than in those who were obese. High inter-observer correlation was found concerning SAD measurement (r = 0.99, P < 0.001). Intra- and inter-observer precision as evaluated by coefficient of variation and intraclass correlation coefficient for SAD measurement was very high. CONCLUSION: Our study shows the usefulness of SAD by anthropometry to predict visceral fat and its very high inter- and intra-observer precision.     

Familial clustering of conversion disorder

This paper reports the result of a study conducted in a single family, in which members of three generations were affected by a conversion disorder. The phenotype and the age of onset were very similar in all the family members affected. The etiology is best understood in terms of a genetic condition and as the result of imitation and identification with an affected family member.     

Caloric restriction reverses hepatic insulin resistance in aging rats by decreasing visceral fat

Hyperinsulinemia and increased visceral/abdominal fat (VF) are common features of human aging. To examine the relationships among VF, peripheral, and hepatic insulin sensitivity, we studied 4- and 18-mo-old male Sprague-Dawley rats (n = 42) fed ad libitum (4 AL and 18 AL) or moderately calorie restricted (18 CR) up to 18 mo of age. Total fat mass (FM) and VF were decreased in 18 CR to approximately one-third of that of 18 AL (P < 0.001), while lean body mass (LBM) was unchanged. Most important, 18 CR had more FM (65+/-6 vs. 45+/-6 g) but less VF (7.8+/-0.6 vs. 12.3+/-3.3 g) compared with 4 AL (P < 0.01 for both). Thus, the effects of variable VF on HIS could be assessed, independent of FM and age. Marked hepatic insulin resistance ensued with aging (18 AL) and CR restored hepatic insulin sensitivity to the levels of young rats, while peripheral insulin sensitivity remained unchanged (by insulin clamp of 18 mU/kg/min). In fact, the rates of insulin infusion required to maintain basal hepatic glucose production in the presence of pancreatic clamp were 0.75+/-0.10, 1.41+/-0.13, and 0.51+/-0.12 mU/kg . min, in 4 AL, 18 AL, and 18 CR, respectively (P < 0.01 between all groups), and in 18 CR rats infused with insulin at similar rates as in the 18 AL (1.4 mU/kg/min) hepatic glucose production was decreased by 32% (P < 0. 005). Furthermore, when 18 CR rats were fed AL for 14 d, VF rapidly and selectively increased and severe hepatic insulin resistance was induced. We propose that in this animal model the age-associated decrease in hepatic (rather than peripheral) insulin action is the major determinant of fasting hyperinsulinemia and that increased visceral adiposity plays the major role in inducing hepatic insulin resistance. Thus, interventions designed to prevent the accumulation of VF are likely to represent an effective mean to improve carbohydrate metabolism in aging.     

Accuracy of prediction equations to estimate submaximal VO2 during cycle ergometry: the HERITAGE Family Study

Calcium-binding S100 proteins are thought to play a central role in calcium-mediated signal transduction pathways. They consist of two helix-loop-helix, calcium-binding EF-hand domains. A characteristic feature is their tendency to form homo- and/or heterodimeric complexes. This report presents for the first time a functional "in vivo" approach to the analysis of S100 protein dimerization. Using the two-hybrid system we analyzed the dimerization of MRP8 (S100A8) and MRP14 (S100A9), two S100 proteins expressed in myeloid cells. It is reported that the MRP8-MRP14 heteromer is the clearly preferred complex in both man and mouse. The ability to homodimerize, however, appears to be restricted to the murine MRPs. Interaction analysis of chimeric murine/human MRP14 proteins indicates, that the C-terminal EF-hand domain plays a prominent role in MRP8-MRP14 interaction and determines the specificity of dimerization. Site-directed mutagenesis of four evolutionary conserved hydrophobic amino acids, which have been recently supposed to be essential for S100 protein dimerization, suggests that at least one of these, namely the most N-terminal located residue, is not critical for dimerization.     

Familial clustering of obesity and breast cancer

One of the most striking characteristics of breast cancer (BC) is a tendency to familial aggregation. In order to evaluate whether familial clustering of obesity could account, at least in part, for the familial aggregation of BC, we compared the adult body size of entire sets of first-degree relatives belonging to 60 families with two or more cases of BC (case families) and 120 BC-free families (control families). Case families included an index case recently admitted for primary BC who had a confirmed first-degree family history for the disease. Control families included one population-based healthy index control with no family history and age-matched (2:1) to index cases. Index cases and controls, recruited from a pool of participants in a large case-control study, completed a questionnaire covering their own body size history as well as that of each of their first-degree relatives (598 case and 1,128 control relatives) using a validated system of body silhouette drawings. The odds ratio (OR) for premenopausal familial BC associated with having one parent markedly obese compared to none was 0.17 (95% confidence interval [CI] 0.04-0.65), while having both parents obese resulted in an OR of 0.25 (95% CI 0.04-1.56). Obesity among siblings was not related to premenopausal familial BC risk nor was familial obesity a significant predictor of familial BC after menopause. Index cases from both menopausal groups tended to be thinner than their unaffected relatives at age 40 years and thereafter. The inverse relationship between parental obesity and premenopausal BC risk is concordant with the protective effect of obesity on early-onset BC previously reported at the individual level.     

Somatovisceral interactions in visceral perception: abdominal masking of colonic stimuli

Clinical and experimental evidence on referred pain and spinal-afferent convergence demonstrates a close relationship between visceral and somatosensory perception, which is important for current models of symptom perception and central body representation. The study uses a psychophysical approach to quantify these interactions at the perceptual level, taking into account problems of comparable intermodal scaling and the role of awareness. An experiment on somatosensory masking of distension stimuli in the colon is reported in which a multiple staircase method of forced choice discrimination with concurrent sensation ratings was employed. Results showed perceptual masking of visceral by abdominal stimuli but not vice versa. The masking effect was not enhanced by intratomal placement of the abdominal stimulus in the lower left quadrant. This contradicts the spinal sensory convergence model and points to perceptual interactions at higher brain levels. Loglinear analysis of relations between discrimination and subjective sensation revealed qualitative differences of somatovisceral perception at the preconscious as compared to the conscious level. This argues for a two-process model of integrative body perception.     

Effect of visceral fat accumulation on uric acid metabolism in male obese subjects: visceral fat obesity is linked more closely to overproduction of uric acid than subcutaneous fat obesity

We investigated the relationship between uric acid (UA) metabolism and fat distribution in 36 obese men with a mean +/- SD age of 38 +/- 16 years and mean body-mass index (BMI) of 34 +/- 4 kg/m2. Subjects were divided into two groups: subcutaneous fat obesity (SFO) and visceral fat obesity (VFO), according to their abdominal fat distribution based on the results of computed tomography (CT). SFO was defined as having a ratio of visceral fat area (VFA) to subcutaneous fat area (V/S) of less than 0.4, and VFO was defined as having a V/S ratio > or = 0.4. The levels of serum total cholesterol (T-Chol), triglyceride (TG), and fasting plasma glucose (FPG), and the diastolic blood pressure (dBP) were significantly higher in the VFO group than in the SFO group. Serum UA levels were much higher in both the SFO and VFO groups than in the non-obese control group (492 +/- 107 and 474 +/- 90 v 309 +/- 48 micromol/L, respectively). The 24-hour urinary urate excretion (u-UA24h) and the UA clearance (Cua) to creatinine clearance (Ccr) ratio were significantly higher in the VFO group than in the SFO group (3.75 +/- 1.43 v 2.69 +/- 1.12 mmol/d, P < .05; and 5.9% +/- 2.0% v 3.6% +/- 1.7%, P < .001, respectively). The frequency of hyperuricemia was markedly higher in both the SFO and VFO groups compared with the control group (71% and 73% v 0%, respectively). Although the high serum UA level seemed to be related to low u-UA24h in 80% of SFO subjects with hyperuricemia, this was the case in only 10% of VFO subjects. While 44% of VFO subjects with hyperuricemia were designated as an overproduction type. These results suggest that the mechanism of hyperuricemia in obesity may be affected by the difference in body fat distribution and that the assessment of body fat distribution and types of hyperuricemia is crucial for the treatment of obese patients with hyperuricemia.     

Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels

Human and rat pineal melatonin secretion decline with aging, whereas visceral fat and plasma insulin levels increase. Melatonin modulates fat metabolism in some mammalian species, so these aging-associated melatonin, fat and insulin changes could be functionally related. Accordingly, we investigated the effects of daily melatonin supplementation to male Sprague-Dawley rats, starting at middle age (10 months) and continuing into old age (22 months). Melatonin was added to the drinking water (92% of which was consumed at night) at a dosage (4 microg/ml) previously reported to attenuate the aging-associated decrease in survival rate in male rats, as well as at a 10-fold lower dosage. The higher dosage produced nocturnal plasma melatonin levels in middle-aged rats which were 15-fold higher than in young (4 months) rats; nocturnal plasma melatonin levels in middle-aged rats receiving the lower dosage were not significantly different from young or middle-aged controls. Relative (% of body wt) retroperitoneal and epididymal fat, as well as plasma insulin and leptin levels, were all significantly increased at middle age when compared to young rats. All were restored within 10 weeks to youthful (4 month) levels in response to both dosages of melatonin. Continued treatment until old age maintained suppression of visceral (retroperitoneal + epididymal) fat levels. Plasma corticosterone and total thyroxine (T4) levels were not significantly altered by aging or melatonin treatment. Plasma testosterone, insulin-like growth factor I (IGF-I) and total triiodothyronine (T3) decreased by middle age; these aging-associated decreases were not significantly altered by melatonin treatment. Thus, visceral fat, insulin and leptin responses to melatonin administration may be independent of marked changes in gonadal, thyroid, adrenal or somatotropin regulation. Since increased visceral fat is associated with increased insulin resistance, diabetes, and cardiovascular disease, these results suggest that appropriate melatonin supplementation may potentially provide prophylaxis or therapy for some prominent pathologies associated with aging.     

Leptin selectively decreases visceral adiposity and enhances insulin action

Intraabdominal adiposity and insulin resistance are risk factors for diabetes mellitus, dyslipidemia, arteriosclerosis, and mortality. Leptin, a fat-derived protein encoded by the ob gene, has been postulated to be a sensor of energy storage in adipose tissue capable of mediating a feedback signal to sites involved in the regulation of energy homeostasis. Here, we provide evidence for specific effects of leptin on fat distribution and in vivo insulin action. Leptin (LEP) or vehicle (CON) was administered by osmotic minipumps for 8 d to pair-fed adult rats. During the 8 d of the study, body weight and total fat mass decreased similarly in LEP and in CON. However, while moderate calorie restriction (CON) resulted in similar decreases in whole body (by 20%) and visceral (by 21%) fat, leptin administration led to a specific and marked decrease (by 62%) in visceral adiposity. During physiologic hyperinsulinemia (insulin clamp), leptin markedly enhanced insulin action on both inhibition of hepatic glucose production and stimulation of glucose uptake. Finally, leptin exerted complex effects on the hepatic gene expression of key metabolic enzymes and on the intrahepatic partitioning of metabolic fluxes, which are likely to represent a defense against excessive storage of energy in adipose depots. These studies demonstrate novel actions of circulating leptin in the regulation of fat distribution, insulin action, and hepatic gene expression and suggest that it may play a role in the pathophysiology of abdominal obesity and insulin resistance.     

Computed axial tomographic scan measurement of abdominal fat distribution and its correlation with anthropometry and insulin secretion in healthy Asian Indians

Asian Indians have high insulin resistance, hyperinsulinemia, a high prevalence of diabetes, and a high waist to hip ratio (WHR), although the rate of obesity is low. WHR and visceral fat (VF) are highly correlated, and both are associated with insulin resistance. This study was performed to determine the normal ranges of abdominal fat distribution (subcutaneous [SF] and VF) in nondiabetic South Indians and also to study its correlations with WHR, plasma insulin, and metabolic profiles. Fat areas were measured by computed axial tomographic scan at the L4 to L5 level. Mean areas of SF and VF in men and women in this study were similar to the values in white populations. Women had significantly less VF than men. Gender differences were observed in the contribution of fat areas to anthropometric, hormonal, and metabolic variables. In general, in men, total fat (TF) area showed significant independent correlation with body mass index (BMI), WHR, and total cholesterol, and VF correlated with insulin secretion. In women, TF and BMI were correlated and SF showed a correlation with total cholesterol. Insulin secretion in women did not show a correlation with fat areas.     

Optimal exposure of the proximal abdominal aorta: a critical appraisal of transabdominal medial visceral rotation

PURPOSE: Adequate exposure of the upper abdominal aorta and its branches is a necessary prelude to safe and durable reconstruction of this aortic segment. Although a variety of approaches to this exposure have been described, few outcome data are available to assess the benefits and limitations of the different exposure options. In this series we report the results of the transabdominal medial visceral rotation (MVR) approach to exposure of the paramesenteric and pararenal aorta. METHODS: One hundred eight operations were performed in 104 patients, representing 19.5% of all aortic reconstructions during a 5.5 year interval. Most patients had hypertension (n = 77, 71.3%) or a history of smoking (n = 83, 76.9%). Heart disease was present in one third of patients (n = 33) and a similar proportion had abnormal renal function (elevated creatinine level) before operation (n = 40, 37.0%). One third of patients (n = 34) had undergone previous aortic or aortic branch reconstruction. Eighty percent of procedures were elective (n = 87). Seventy-one patients (65.7%) required renal revascularization, usually for hypertension or elevated creatinine levels, whereas 37 patients (34.3%) underwent visceral reconstruction, most often for symptoms of chronic mesenteric ischemia. Only 22 patients required isolated infrarenal aortic repair. Most of the aortic lesions were aneurysmal (n = 42). Eighty percent of procedures (n = 88) required suprarenal or more proximal aortic clamping. The most frequently used reconstruction techniques were bypass (n = 39, 36.1%), endarterectomy (n = 18, 16.7%), or both (n = 23, 21.3%). RESULTS: There were four intraoperative deaths (3.7%) and 15 postoperative deaths (13.9%). All intraoperative deaths and four postoperative deaths were related to hemorrhage and its complications. Visceral infarction was the most frequent cause of postoperative death. The intraoperative complications that were determined to be related to the medial visceral rotation approach included splenic injury (n = 23, 21.3%), one aortic injury, and one adrenal injury. The aortic injury was associated with substantial intraoperative bleeding and subsequent death. The postoperative complications resulting from MVR included pancreatitis (n = 5), which contributed to death in two patients, and possibly some of the cases of visceral infarction not associated with visceral reconstruction. The other common postoperative complications, cardiac (n = 25, 24.0%), pulmonary (n = 32, 30.8%), renal (n = 20, 19.2%), and infectious (n = 17, 16.3%), were attributed to the procedures performed. CONCLUSIONS: Transabdominal MVR exposure of the upper abdominal aorta provides unrestricted access to the visceral branch-bearing segment of the aorta and places no limitations on the choice of arterial reconstruction technique. The associated morbidity and mortality rates are typical of patients undergoing these complex vascular repairs, but the frequency of splenic injury and postoperative pancreatitis is increased.     

Familial clustering of end-stage renal disease in blacks with lupus nephritis

The factors that determine a patient's susceptibility to specific target organ involvement in systemic lupus erythematosus (SLE) remain unknown. Lupus nephritis can be a particularly devastating complication, with an increased mortality and the risk of progressive renal damage resulting in end-stage renal disease (ESRD). This analysis was performed to determine whether renal disease aggregated in select families or was a sporadic complication in patients with SLE. We compared the family history of ESRD in 50 patients with SLE complicated by lupus nephritis with 37 controls who had SLE but lacked nephritis after a mean follow-up duration of more than 11 years. The frequency of relatives with ESRD in the lupus nephritis cases was compared with that in controls using Fisher's exact test (significance at P < or = 0.05). Fifty percent (25) of the 50 lupus nephritis patients were black and 50% (25) white, in contrast to 35% (13) and 65% (24) of the 37 lupus non-nephropathy controls, respectively. A first-, second-, or third-degree relative with ESRD was present in 16% (eight) of the 50 lupus nephritis cases and in 0% of the 37 SLE non-nephropathy controls (P = 0.019, Fisher's exact test, two-tail). Twenty-eight percent (seven) of the 25 black patients with lupus nephritis had relatives with ESRD compared with 0% of the 13 black lupus non-nephritis controls (P = 0.07). Only one of the eight relatives with ESRD had SLE or a collagen vascular disease. Lupus nephritis patients and the non-nephritis controls had similar ages (mean +/- SD: 38.5 +/- 10.0 years v 46.6 +/- 11.8 years; P = 0.28), family sizes (6.27 +/- 2.61 first-degree relatives v 6.35 +/- 3.25 first-degree relatives; P = 0.16), and duration of SLE (9.26 +/- 5.94 years v 11.35 +/- 6.43 years; P = 0.60). Familial clustering of ESRD was observed in black patients with SLE who had nephritis. This was unlikely to be related to differences in patient age, family size, or duration of SLE. This data, coupled with the known familial aggregation of ESRD in blacks with hypertensive and diabetic ESRD, supports the contention that genetic factors contribute to the familial clustering. The presence of relatives with etiologies of ESRD other than SLE suggests that there is an inherited susceptibility to progressive renal failure, independent of the etiology of ESRD.     

Amount of G-protein alpha-subunit in rat white adipocytes: lack of difference between subcutaneous and visceral fat

It has been the purpose of this study to examine possible differences in the amount of stimulatory (Gs) and inhibitory (Gi) G-protein alpha-subunits (measured with a quantitative enzyme-linked immunosorbent assay in fat cell membrane preparation) between subcutaneous and intra-abdominal regions in rats. The lipolytic response to isoproterenol and the number of beta-adrenergic binding sites were also examined. These parameters were all evaluated simultaneously in subcutaneous (inguinal), epididymal and perirenal fat samples collected from six male Sprague-Dawley rats. The membrane contents of the Gs and Gi alpha-subunits were similar in the three depots. Moreover, no difference was found among the different regions with regard to isoproterenol-stimulated glycerol release and beta-adrenoceptor number, expressed per cell number. In conclusion, the present study shows for the first time in rats that the abundance of inhibitory and stimulatory G-protein alpha-subunits is similar in subcutaneous and in visceral adipocytes. Moreover, the number of beta-adrenoceptors and the lipolytic response to isoproterenol do not show significant variations with the anatomical site. As the present results are apparently in contrast with those obtained previously in human adipocytes, there is a possibility that the different results observed in rat and in human fat cells could be explained by species differences.     

Relation between atherosclerotic risk factors and abdominal wall fat thickness

Dilated cardiomyopathy is a common cause of heart failure with systolic dysfunction. Medications used to treat this condition are usually for symptomatic relief. We studied the effect of atenolol in heart failure caused by dilated cardiomyopathy in a double blinded randomized fashion. There were 17 males and 5 females. All patients underwent right and left heart catheterization, coronary angiography, endomyocardial biopsy, exercise testing and doppler echocardiography. By 3 months, atenolol significantly reduced resting and exercise heart rate and pulmonary capillary wedge pressure. There was no difference in exercise capacity. We conclude from this study that atenolol improve hemodynamic condition in patients with dilated cardiomyopathy without improving exercise capacity during this short observation period.     

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.     

Dynamic accumulation of neutrophils in lungs and visceral organs during early abdominal sepsis in the pig

Activation and accumulation of polymorphonuclear leukocytes (PMNs, neutrophils) in the lungs is considered an important mechanism in the pathogenesis of pulmonary dysfunction in association with sepsis. It probably constitutes only part of a general cellular response; and a corresponding reaction has been implicated in other organs during sepsis (e.g., the liver). In this experiment a model was developed that allows study of the dynamic PMN reaction in the lungs and visceral organs during early abdominal sepsis. The animals were divided into two groups. In the septic group (n = 8) a bacterial challenge was attempted through the intraperitoneal administration of Escherichia coli (1 x 10(11)/kg). Five animals served as controls. All animals in the septic group developed bacteremia, leukopenia, and a hypodynamic circulatory response. PMNs were selectively labeled with 111In-oxine. The activity over the organs was followed dynamically with a gamma camera. The animals subjected to peritonitis exhibited a significant increase in 111In-oxine activity (i.e., neutrophil trapping) in the lungs, compared to the controls at 40 minutes and onward during the observation period. A similar picture was seen over the liver and abdomen, with significance after 70 minutes. The findings in this study indicate that accumulation of PMNs is an early phenomenon not only in the lungs but also in the liver during the development of sepsis. The present model offers possibilities for further studies of the cellular reactions during sepsis.     

Enhanced expression of PAI-1 in visceral fat: possible contributor to vascular disease in obesity

The presence of obesity increases the risk of thrombotic vascular diseases. The role of fat accumulation and its effect on plasminogen activator inhibitor-1 (PAI-1) levels was investigated in humans and animals. Plasma PAI-1 levels were closely correlated with visceral fat area but not with subcutaneous fat area in human subjects. PAI-1 mRNA was detected in both types of fat tissue in obese rats but increased only in visceral fat during the development of obesity. These data suggest that an enhanced expression of the PAI-1 gene in visceral fat may increase plasma levels and may have a role in the development of vascular disease in visceral obesity.