Glucose uptake in human adipose tissue

One hundred grams of glucose with 50 microCi U-14C-glucose were given orally to 17 women with widely varying amounts of body fat. Radioactivity and glucose metabolism in vitro were then measured in adipose tissue obtained by needle biopsies in the abdominal and femoral regions after four hours. Radioactivity in triglycerides was then measured in repeated biopsies 1 day, 1 week, and monthly up to 7 months after glucose administration. Glucose label in triglycerides after four hours was higher in abdominal than femoral adipocytes in obese women. It increased slightly during the following week, and then decreased exponentially with a half-life of 12 months in the abdominal region and 19 months in the femoral region. Uptake of glucose carbon in total body fat was estimated from the triglyceride label measured and determinations of body fat mass, and found to be in the order of less than 4% of given glucose. The studies in vitro suggested that much of the glucose taken up in adipose tissue is converted to lactate. If this is the case in vivo, then glucose uptake in adipose tissue might well be of significance for total body glucose homeostasis, particularly in obese subjects, amounting to maximally perhaps one third to one half of the oral glucose given. The majority of this glucose uptake would then, however, leave adipose tissue again as lactate. The shorter half-life of label in abdominal adipocytes is in agreement with findings of increased lipolysis in these adipocytes in vitro.     

The regulation of body fat distribution and the modulation of insulin action

Body fat distribution may determine insulin resistance and its metabolic syndrome in humans, independent of obesity. Surgical removal of visceral fat (VF) in obese rats was associated with decreased leptin plasma levels and its gene expression in subcutaneous fat (SC). Chronic leptin treatment to rats decreased VF specifically supporting the role of leptin in determining fat distribution. Surgical removal of selected VF provided direct evidence of improved in vivo insulin action on hepatic glucose production (HGP) by over 2-fold vs sham-operated control. The impact of decreased VF on improved in vivo insulin action was further supported by obtaining similar decreases in VF by treating rats with leptin (Lep), beta3-aderenoreceptor agonist, or by severe caloric restriction (CR). All these three interventions improved insulin action on the modulation of HGP and were mostly attributed to preservation of hepatic glycogen stores. Because free fatty acids (FFA) plasma levels were unchanged, this effect may not be mediated portally by substrates. Improved peripheral insulin sensitivity and glycogen synthesis was demonstrated only in Lep. These data suggest that VF is a major determinant of hepatic insulin action. In obese rats, the ability of leptin to prevent visceral adiposity and its own expression is attenuated. Thus, the failure of leptin to regulate fat distribution and its own secretion suggest that 'leptin resistance' may be a pathologic feature in obesity.     

Glucose metabolism in obesity: influence of body fat distribution

The dose-response relationships between portal venous insulin concentrations and hepatic glucose production and between peripheral insulin concentrations and peripheral glucose utilization were determined in 8 nonobese and 17 obese premenopausal women with either upper or lower body fat localization. The glucose production dose-response curves for the two obese groups were shifted to the right at all levels of portal insulinemia. The upper body obese women had a greater rightward shift compared to the lower body obese women. The peripheral glucose utilization dose-response curve was shifted to the right in the lower body obese women, but maximal glucose utilization was normal. The upper body obese women had both a greater rightward shift and a marked reduction in maximal glucose utilization. The insulin concentrations that had half-maximal effects on glucose production and utilization were similar in each group. These results indicate that the liver is not inherently more sensitive to insulin than peripheral tissues. Obesity is associated with a moderate diminution of hepatic and peripheral insulin sensitivity. Upper body fat localization in obese women is characterized by a greater diminution in insulin sensitivity and decline in peripheral insulin responsivity than is lower body fat localization. The marked peripheral insulin resistance in the former group may account for the increased prevalence of glucose intolerance.     

Lipid profile, BMI, body fat distribution, and aerobic fitness in men with metabolic syndrome

Obesity, impaired glucose tolerance, type 2 diabetes, hyperlipidemia, hypertension, and insulin resistance are wellknown components of metabolic syndrome and are associated to increased cardiovascular morbidity. The present study aimed to evaluate the relationships between cardiorespiratory fitness, body fat distribution, and selected coronary heart disease risk factors. A total of 22 untrained subjects affected by one or more features of metabolic syndrome and without clinical history of cardiovascular disease were studied. Nondiabetic subjects underwent an oral glucose tolerance test for glucose and insulin measurement; fasting glucose and insulin were measured in diabetic patients. Complete lipid profile, thyroid hormones, and thyroid-stimulating hormone were measured in all subjects. Basal energy expenditure and cardiorespiratory fitness were measured using a K4 analyzer. Cardiorespiratory fitness ( VO(2max)/kg) was assessed using a treadmill graded exercise test. Peak aerobic capacity ( VO(2max)/kg) was predicted by body fat distribution, insulin sensitivity index, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol ( p<0.001). A significant relationship was found between cardiorespiratory fitness ( VO(2max)/kg) and body mass index (BMI), insulin sensitivity index, and LDL cholesterol ( r=0.60, p<0.05; r=0.66, p<0.01 and r=0.54, p<0.05, respectively). Data demonstrated that aerobic fitness is related to metabolic parameters and to body fat distribution, and suggest that its modification may improve well-known predictors of coronary artery disease.     

Urinary catecholamines, plasma insulin and environmental factors in relation to body fat distribution.

The relationship of body fat distribution to insulin and the catecholamines, hormones that affect lipolysis differentially by fat site, was examined within an environmental context, including factors of medication use, physical activity, dietary intake, educational attainment, and age. Four cross-sectional body fat areas (cm2) were determined by three computed tomography (CT) scans (subcutaneous chest fat at the level of the nipples, subcutaneous and intra-abdominal fat at the level of the umbilicus, and subcutaneous left mid-thigh fat) in 191 second-generation Japanese-American men aged 45-74 years. The site-specific fat measurements were first examined in relation to use of beta-adrenergic antagonists, then to fasting plasma insulin and C-peptide levels and to urinary epinephrine and norepinephrine levels from a 24-h urine collection made during usual daily activities. Greater fat stores in the intra-abdominal area, even after adjustment for body mass index (BMI, weight/height2) and presence of coronary heart disease, were found to be related to use of beta-adrenergic antagonists. In men taking no adrenergic antagonists (n = 157), after adjustment for BMI, truncal fat measurements of the chest (partial r = -0.16, P less than 0.05) and intra-abdominal area (partial r = -0.21, P less than 0.05) were found to be inversely related to epinephrine, and intra-abdominal fat (partial r = 0.25, P less than 0.01) alone was directly related to fasting plasma insulin. With respect to other environmental variables, the significant inverse relationship of intra-abdominal fat (adjusted for BMI) with physical activity (partial r = -0.17, P less than 0.05) and the significant difference in intra-abdominal fat by educational attainment (college 102.3 +/- 5.7 vs no college 115.7 +/- 6.1 cm2, P = 0.03) became non-significant with adjustment, using multiple regression analysis, for insulin in the case of physical activity and epinephrine in the case of educational attainment. Thus, intra-abdominal fat showed a unique set of relationships to metabolic parameters which could be further related to certain environmental variables.     

The role of interleukin-6 in insulin resistance, body fat distribution and energy balance.

Interleukin-6 (IL-6) is a central player in the regulation of inflammation, haematopoiesis, immune response and host defense mechanisms. During the last decade, an accumulating amount of data suggested a pivotal role for IL-6 in metabolic processes, thus fortifying the picture of IL-6 as a multifaceted, pleiotropic cytokine. Because of its secretion by adipose tissue and contracting skeletal muscle and its broad action on central and peripheral organs, IL-6 has been termed an adipokine and a myokine. Its quantitative release from adipose tissue results in a subclinical, systemic elevation of IL-6 plasma levels with increasing body fat content, which may be implicated in the proinflammatory state leading to insulin resistance. On the other hand, IL-6 produced in the working muscle during physical activity could act as an energy sensor by activating AMP-activated kinase and enhancing glucose disposal, lipolysis and fat oxidation. In addition, both impaired IL-6 secretion and action are risk factors for weight gain. Thus, IL-6 clearly has lipolytic effects and anti-obesity potential. However, the application of IL-6 itself is at least limited by a narrow therapeutic range and its important function for a balanced inflammatory response. Further studies on the molecular basis of the metabolic effects of IL-6 could elucidate novel therapeutic strategies for custom-designed, IL-6-related substances.     

2型糖尿病患者脂联素和体脂含量及分布与胰岛素敏感性的相关研究

目的　分析脂联素 (ADIPO)与机体脂肪含量、分布及组织胰岛素敏感性 (IS)的关系。　方法　符合 1999年WHO糖尿病诊断标准的 2型糖尿病 (T2DM )患者 4 0例 ,男 16例 ,女 2 4例 ,平均年龄 (5 5± 7)岁 ,体质指数 (BMI) (2 5 0± 2 5 )kg/m2 ,病程 (3± 4 )年。测定常规临床检查项目和血糖、血浆胰岛素水平。按HOMA模型计算胰岛素抵抗 (IR)指数。其中 2 0例患者应用正常血糖高胰岛素钳夹试验测定组织葡萄糖代谢率 (M)。同时测定ADIPO、肿瘤坏死因子α(TNFα)和游离脂肪酸(FFA)水平。应用双能X线测定机体的全身脂肪含量、全身瘦肉组织含量 ,并计算全身脂肪含量百分比。其中 17例患者同时应用核磁共振测定脂肪分布 ,以电子计算机计算腹内脂肪面积 (VFA)、腹部皮下脂肪面积 (SFA) ,并计算VFA/SFA比值。　结果　 (1)肥胖或体脂含量增加的T2DM患者其血浆ADIPO显著降低 ;(2 )腰围或腹内脂肪增加的T2DM患者其血浆ADIPO显著降低 ;(3)T2DM患者ADIPO水平与M值显著正相关 ,与TNFα、FFA呈显著负相关。　结论　T2DM患者体脂含量和分布影响血浆ADIPO水平 ,ADIPO与IS呈显著正相关。     

Demonstration of estrogen receptor subtypes alpha and beta in human adipose tissue: influences of adipose cell differentiation and fat depot localization

A novel ER-subtype, the ER-beta has recently been characterized in various tissues, furthermore five isoforms of the ER-beta are known (ER-beta1--ER-beta5). Using immunoblotting and real- time RT-PCR, ER-alpha and beta were studied in human adipose tissue. The expression of ER-alpha mRNA was equal in subcutaneous gluteal adipose tissue, subcutaneous abdominal and intra-abdominal adipose tissue, similar findings were obtained at the protein level. In contrast the amount of ER-beta1 (protein and mRNA) was significantly lower in intra-abdominal adipose tissue as compared with the subcutaneous adipose tissue (five-fold lower in women, P<0.005 and three-fold lower in men, P<0.005) whereas the expression of ER-beta4 and -beta5 mRNA isoforms were significantly higher in gluteal adipose tissue compared to subcutaneous abdominal adipose tissue. No significant gender differences in ER expression was detected in any of the fat depots investigated. During adipocyte differentiation the expression of ER-alpha, -beta4 and -beta5 mRNA declined, whereas, the expression of ER-beta1 mRNA was constant. In conclusion, the existence of ER-beta isoforms in human adipose tissue was demonstrated and the amount of these receptors was dependent upon fat depot localization, with much reduced expression of ER-beta1 in intra-abdominal adipose tissue compared to subcutaneous adipose tissue. These findings may indicate that estrogens could have differentiation and depot specific effects in human adipose tissue.     

Glucose uptake and perfusion in subcutaneous and visceral adipose tissue during insulin stimulation in nonobese and obese humans

To elucidate the role of adipose tissue glucose uptake in whole-body metabolism, sc and visceral adipose tissue glucose uptake and perfusion were measured in 10 nonobese and 10 age-matched obese men with positron emission tomography using [(18)F]-2-fluoro-2-deoxy-D-glucose, and [(15)O]-labeled water during normoglycemic hyperinsulinemia. Whole-body and skeletal muscle glucose uptake rates per kilogram were lower in obese than in nonobese subjects (P < 0.01). Compared with nonobese, the obese subjects had 67% lower abdominal sc and 58% lower visceral adipose tissue glucose uptake per kilogram of fat. In both groups, insulin stimulated glucose uptake per kilogram fat was significantly higher in visceral fat depots than in sc regions (P < 0.01). Both sc and visceral adipose tissue blood flow expressed per kilogram and minute was impaired in the obese subjects, compared with the nonobese (P < 0.05). Fat masses measured with magnetic resonance images were higher in obese than in nonobese individuals. If regional glucose uptake rates were expressed as per total fat mass, total glucose uptake rates per depot were similar in obese and nonobese subjects and represented 4.1% of whole-body glucose uptake in obese and 2.6% in nonobese subjects (P < 0.02 between the groups). In conclusion, insulin-stimulated glucose uptake per kilogram fat is higher in visceral than in sc adipose tissue. Glucose uptake and blood flow in adipose tissue exhibit insulin resistance in obesity, but because of the larger fat mass, adipose tissue does not seem to contribute substantially to the reduced insulin stimulated whole-body glucose uptake in obesity.     

Hemostatic risk factors and insulin sensitivity, regional body fat distribution, and the metabolic syndrome

Disturbances in the thrombotic and fibrinolytic systems are a feature of insulin resistance, obesity, and the metabolic syndrome. However, there are few studies in which these relationships have been explored in mainly asymptomatic individuals using sophisticated measures of insulin sensitivity and regional adiposity. Variables of the hemostatic system were measured in 106 men (aged 32-68 yr; body mass index, 20-34 kg/m(2)). Insulin sensitivity was measured by minimal model analysis and regional adiposity by dual energy x-ray absorptiometry. Clustering of intercorrelated variables was assessed by the statistical technique of factor analysis. Plasma levels of procoagulant factors VII and X, anticoagulant proteins C and S, and plasminogen activator inhibitor-1 correlated positively with total and percent central body fat (r = 0.25-0.38; P < 0.05) and negatively with insulin sensitivity (except protein S; r = -0.24 to -0.35; P < 0.05). On factor analysis, procoagulant factors VII and X, proteins C and S, and plasminogen activator inhibitor-1 were components of the cluster of variables that explained the greatest proportion of the variance in the data (39.2%). Other variables included in this cluster were those typical of the metabolic syndrome and also serum gamma-glutamyl transferase activity. These results suggest that factors VII and X and proteins C and S are features of the intercorrelated disturbances of the metabolic syndrome. Associations with adiposity and liver enzyme activity suggest the involvement of hepatic fat deposition.     

原发性高血压患者体脂分布与胰岛素抵抗的关系

采用放射免疫分析法测定21例原发性高血压(EH)伴肥胖者,19例单纯性肥胖及16例正常体重者的空腹及口服75g葡萄糖耐量试验(OGTT)的血清胰岛素(INS)和C肽(CP)浓度.以腰臀围比(WHR)作为估计腹型肥胖的指标;以胰岛素敏感性指数(ISI)作为胰岛素抵抗(IR)指标.结果显示,在总体脂相似的情况下,EH伴肥胖者腹部脂肪蓄积较多,循环胰岛素清除率下降明显.提示EH伴肥胖患者较单纯性肥胖者有更严重的IR和高胰岛素血症(HI).EH患者的IR不但与总体脂增多有关,而且与体脂分布关系密切.     

Pubertal alterations in growth and body composition. VI. Pubertal insulin resistance: relation to adiposity, body fat distribution and hormone release

OBJECTIVE: To investigate the independent influence of alterations in fat mass, body fat distribution and hormone release on pubertal increases in fasting serum insulin concentrations and on insulin resistance assessed by the homeostasis model (HOMA). DESIGN AND SUBJECTS: Cross-sectional investigation of pre- (n=11, n=8), mid- (n=10, n=11), and late-pubertal (n=10, n=11) boys and girls with normal body weight and growth velocity. MEASUREMENTS: Body composition (by a four-compartment model), abdominal fat distribution and mid-thigh interfascicular plus intermuscle (extramyocellular) fat (by magnetic resonance imaging), total body subcutaneous fat (by skinfolds), mean nocturnal growth hormone (GH) release and 06:00 h samples of serum insulin, sex steroids, leptin and insulin-like growth factor-I (IGF-I). RESULTS: Pubertal insulin resistance was suggested by greater (P<0.001) fasting serum insulin concentrations in the late-pubertal than pre- and mid-pubertal groups while serum glucose concentrations were unchanged and greater (P<0.001) HOMA values in late-pubertal than pre- and mid-pubertal youth. From univariate correlation fat mass was most related to HOMA (r=0.59, P<0.001). Two hierarchical regression models were developed to predict HOMA. In one approach, subject differences in sex, pubertal maturation, height and weight were held constant by adding these variables as a block in the first step of the model (r(2)=0.36). Sequential addition of fat mass (FM) increased r(2) (r(2)((inc)remental)=0.08, r(2)=0.44, P<0.05) as did the subsequent addition of a block of fat distribution variables (extramyocellular fat, abdominal visceral fat, and sum of skinfolds; r(2)(inc)=0.11, r(2)=0.55, P<0.05). Sequential addition of a block of hormone variables (serum IGF-I and log((10)) leptin concentrations; r(2)(inc)=0.04, P>0.05) did not reliably improve r(2) beyond the physical characteristic and adiposity variables. In a second model, differences in sex and pubertal maturation were again held constant (r(2)=0.25), but body size differences were accounted for using percentage fat data. Sequential addition of percentage body fat (r(2)((inc)remental)=0.11, r(2)=0.36, P<0.05), then a block of fat distribution variables (percentage extramyocellular fat, percentage abdominal visceral fat, and percentage abdominal subcutaneous fat; r(2)(inc)=0.08, r(2)=0.44, P=0.058), and then a block of serum IGF-I and log((10)) leptin concentrations (r(2)(inc)=0.07, r(2)=0.51, P<0.05) increased r(2). Mean nocturnal GH release was not related to HOMA (r=-0.04, P=0.75) and therefore was not included in the hierarchical regression models. CONCLUSION: Increases in insulin resistance at puberty were most related to FM. Accumulation of fat in the abdominal visceral, subcutaneous and muscular compartments may increase insulin resistance at puberty beyond that due to total body fat. Serum concentrations of leptin and IGF-I may further modulate HOMA beyond the effects of adiposity and fat distribution. However, the results are limited by the cross-sectional design and the use of HOMA rather than a criterion measure of insulin resistance.     

Effect of body mass index and fat distribution on insulin sensitivity, secretion, and clearance in nonobese healthy men.

The effects of variation in body mass index (BMI; kg/m2) and body fat topography on insulin sensitivity, secretion, and clearance were determined in a group of 146 nonobese nondiabetic males. Volunteers underwent an i.v. glucose tolerance test, with determination of plasma glucose, insulin, and C-peptide levels. BMI was taken as a measure of overall adiposity, while skinfold thickness ratios were used to assess the centrality of fat distribution and the localization of central fat within the trunk. Measurements of insulin sensitivity, secretion, and clearance were obtained by mathematical modelling of the i.v. glucose tolerance test concentration profiles. Increasing BMI and centrality of fat distribution had no significant effect on glucose tolerance, but were independently associated with diminished insulin sensitivity and increased insulin secretion. The elevation in secretion occurred almost entirely during the second phase of pancreatic insulin release. These results show that the variations in insulin sensitivity and secretion that have often been reported in obesity are also present in a group within the normal range of BMI. However, the absence of any decrease in hepatic uptake, also reported in the obese, indicates that this might be an additional mechanism recruited to maintain glycemic control at higher levels of adiposity. Localization of central fat in the lower trunk was correlated with elevated first phase insulin secretion, but no concomitant change in insulin sensitivity. There may, therefore, be a direct effect of the distribution of central fat on insulin secretion.     

BMI inaccurately reflects total body and abdominal fat in Tongans

It has been noted since the earliest European contact that Polynesian body shape and size differ from those of Europeans. The muscular build of Polynesians, such as Tongans, raises questions as to the accuracy of simple anthropometric indicators, validated for use in European populations, in Polynesians. Body mass index (BMI), total body fat and an abdominal fat window were measured in a sample of Tongan [28 male (M), 28 female (F)] and Australian Caucasian adults (39 M, 46 F), with standard anthropometric and densitometric methods. Tongan males (BMI, 32.8+/-4.6 kg/m(2)) were heavier than Australian males (BMI, 27.1+/-3.7 kg/m(2)); but differences in total body percent fat (28.9+/-8.3 vs. 25.9+/-8.1, p=0.15), abdominal fat (1.84+/-0.69 vs. 1.55+/-0.60 kg, p=0.07) and abdominal percent fat (30.3+/-8.6 vs. 28.5+/-8.3, p=0.40) were non-significant. Tongan females (BMI, 34.3+/-5.5 kg/m(2)) were also heavier than their Australian counterparts (BMI, 26.2+/-6.3 kg/m(2)); with the difference in total body percent fat (41.9+/-5.2 vs. 38.7+/-8.9, p=0.05) and abdominal percent fat (39.3+/-4.8 vs. 33.6+/-8.9, p=0.001) less than expected, given the difference in BMI. This study demonstrates significant body composition variations between Tongans and Caucasians.     

The relative contribution of androgens and insulin in determining abdominal body fat distribution in premenopausal women.

To investigate the relative contribution of insulin and sex hormones in determining the abdominal pattern of fat distribution in premenopausal women, five groups of age-matched subjects were examined: Group 1 consisted of 14 normal weight eumenorrheic women (NO); Group 2 of 9 obese eumenorrheic women (OB); Group 3 of 14 normal weight hyperandrogenic women with polycystic ovary syndrome (NO-HA); Group 4 of 10 obese hyperandrogenic women with polycystic ovary syndrome (OB-HA) and, finally, Group 5 of 10 obese hyperandrogenic women with polycystic ovary syndrome and acanthosis nigricans (OB-HA-AN). Both the two normal weight groups and the three obese groups were matched for body mass index values. Sex hormone pattern showed significantly higher LH and testosterone levels in hyperandrogenic women with respect to NO and OB women but obese hyperandrogenic groups (OB-HA and OB-HA-AN) presented significantly lower LH concentrations than NO-HA. Fasting and glucose-stimulated insulin levels were significantly higher in OB than NO, in OB-HA and OB-HA-AN than in OB and NO-HA, and in OB-HA-AN than in OB-HA, without any significant difference between OB and NO-HA. Body fat distribution, expressed by the waist to hip ratio (WHR), showed progressively higher values (p less than 0.01) from NO to OB, NO-HA, OB-HA and, particularly, OB-HA-AN women. Determination coefficients r2 obtained from simple regression analysis showed that the sum of insulin values during the glucose tolerance test and testosterone levels had a more significant power in determining WHR variability.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of body fat distribution in the decline in insulin sensitivity and glucose tolerance with age.

The relationships of body composition and physical fitness [maximal aerobic capacity (VO2max)] to the decline in insulin sensitivity with age were examined in healthy older (47-73 yr; n = 36) and young (19-36 yr; n = 13) men. In 18 older men with normal glucose tolerance (OGTT), glucose disposal rates (M) during hyperinsulinemic euglycemic clamps correlated negatively with the waist to hip ratio (WHR; r = -0.77; P < .001) and percent body fat (r = -0.46; P < 0.05) and positively with VO2max (r = 0.54; P < 0.05), but not with age. Similar relationships existed in the 36 older men with a spectrum of OGTT responses; however, only WHR was independently related to M (r2 = 0.32; P < 0.01). In the older men with normal OGTT, M (mean +/- SEM, 7.88 +/- 0.43 mg/kg fat-free mass.min) was not different from that in the young men (8.56 +/- 0.47; P = NS). Furthermore, in older and young men with normal OGTT matched for WHR, percent fat, or VO2max, glucose disposal was comparable at sequential 15-min intervals during the clamp and in its relationship to insulin concentrations at the tissue level (multicompartmental analysis). In contrast, despite higher steady state plasma insulin levels during the clamp, M was significantly lower in the older men with a higher WHR, greater percent fat, lower VO2max, or impaired OGTT. Thus, in healthy older men up to the age of 73 yr, insulin sensitivity and glucose tolerance are affected primarily by the regional body fat distribution, not age, obesity, or VO2max.     

Inheritance of the amount and distribution of human body fat

Despite recent advances, controversy continues about the inheritance of the amount and distribution of body fat. We have studied the genetic and 'cultural' (nongenetic) transmission between generations of the body mass index, sum of six skinfold measurements, percentage of body fat, fat mass, fat-free mass, and two indicators of fat distribution. These data were obtained in 1698 members of 409 families, which included the following pairs of family members: spouses, (maximum number of pairs = 348), foster parent-adopted child (322), siblings by adoption (120), first-degree cousins (95), uncle/aunt-nephew/niece (88), parent-natural child (1239), full sibs (370), dizygotic twins (69), and monozygotic twins (87). The total transmissible variance ranged from about 40 percent for the amount of subcutaneous fat to 60 percent for the pattern of subcutaneous fat distribution. Biological inheritance accounted for only 5 percent of the variance for subcutaneous fat and the body mass index, but 20 to 30 percent for the percentage of body fat, fat mass, fat-free mass, and fat distribution. These data suggest that the amount of internal fat is influenced by heredity more than the amount of subcutaneous fat. Furthermore, we consistently found that nongenetic influences are quite important in determining the amount and distribution of body fat in the population. These estimates may differ in the subpopulation of obese individuals.     

HLA system, body fat and fat distribution in children and adults

The association between the genotypes and the alleles at the A, B or C locus of the HLA system and body fat was studied in a total of 1578 individuals subdivided in four cohorts: adult males (n greater than or equal to 204), adult females (n greater than or equal to 184), boys and male adolescents (n greater than or equal to 282), and girls and female adolescents (n greater than or equal to 257). None of these subjects were grossly obese or had known metabolic disorders. Percent body fat from underwater weighing, subcutaneous fat from 6 skinfold measurements, trunk fat (3 skinfolds) and extremity fat (3 skinfolds) were considered in the analysis. Although a few significant associations were encountered, the lack of consistency across samples suggested that they were probably random and biologically not meaningful. The same negative findings were found for the ratio of trunk subcutaneous fat to extremity subcutaneous fat and the ratio of subcutaneous fat (6 skinfolds) to total fat mass. Earlier reports indicating a significant association between high body fat content and antigens B18, Bw35 or Cw4 were not supported by the results of this study. It was concluded that no consistent pattern of association emerged between genotypes or alleles of the HLA system and percent body fat, subcutaneous fat or fat distribution in children and adults of both sexes.