Total Adipose Tissue Mass Research Articles

Comparison of conjugated linoleic acid (CLA) and conjugated nonadecadienoic acid (CNA) with regard to lipid metabolism in mice

It has been reported that conjugated nonadecadienoic acid (CNA) exhibits modulation of body fat with mechanisms that are similar to those of CLA. In this current investigation, we compared the effects of CNA and CLA on various feeding period, in particular studying lipid metabolism from white adipose tissue. One hundred thirty 10 week‐old male CD‐1 mice were fed a semi‐purified powdered diet with 20% total fat based on the AIN‐93 diet. After a 2‐week adaptation period, mice were randomly assigned into control and 2 treatment groups (0.5 w/w% CLA and 0.1 w/w% CNA). Relative mRNA expression of peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), acetyl‐CoA carboxylase (ACC), fatty acid synthase (FAS), hormone‐sensitive lipase (HSL), and glucose transporter 4 (GLUT4) were determined at week 0, 2, 4, 8, and 12 by real time PCR from the white adipose tissue. The effect of CNA treatment on total adipose tissue mass was less effective than CLA over time. HSL mRNA expression was significantly increased by CNA at week 8 and 12, while CLA had no effect at any time point. PPAR‐γ expression was significantly decreased by both CNA and CLA after week 2 and 4, respectively, and the decreased expression of PPAR‐γ was maintained for 12 weeks. FAS expression was enhanced by CNA during week 4 and 8 and by CLA at all time points. ACC expression was increased by CNA longer than 8 weeks, while CLA increased it at all time points. GLUT4 expression was decreased at week 8 by CNA but not by CLA. In conclusion, CNA reduces body fat mass similar to CLA. Although CNA shares mechanisms with CLA on body fat control and lipid metabolism, there were differences in the effects on lipid metabolism between CNA and CLA over time. Supported by AHA SDG and ILSI North America

Loss of Total and Visceral Adipose Tissue Mass Predicts Decreases in Oxidative Stress After Weight‐loss Surgery

It is not known whether there are mechanisms linking adipose tissue mass and increased oxidative stress in obesity. This study investigated associations between decreasing general and abdominal fat depots and oxidative stress during weight loss. Subjects were severely obese women who were measured serially at baseline and at 1, 6 (n = 30), and 24 months (n = 18) after bariatric surgery. Total fat mass (FAT) and volumes of visceral (VAT) and subcutaneous abdominal adipose tissue (SAT) were related to plasma concentrations of derivatives of reactive oxidative metabolites (dROMS), a measure of lipid peroxides and oxidative stress. After intervention, BMI significantly decreased, from 47.7 +/- 0.8 kg/m(2) to 43.3 +/- 0.8 kg/m(2) (1 month), 35.2 +/- 0.8 kg/m(2) (6 months), and 30.2 +/- 1.2 kg/m(2) (24 months). Plasma dROMS also significantly deceased over time. At baseline, VAT (r = 0.46), FAT (r = 0.42), and BMI (r = 0.37) correlated with 6-month decreases in dROMS. Similarly, at 1 month, VAT (r = 0.43) and FAT (r = 0.41) correlated with 6-month decreases in dROMS. Multiple regression analysis showed that relationships between VAT and dROMS were significant after adjusting for FAT mass. Increased plasma dROMS at baseline were correlated with decreased concentrations of high-density lipoprotein (HDL) at 1 and 6 months after surgery (r = -0.38 and -0.42). This study found longitudinal associations between general, and more specifically intra-abdominal adiposity, and systemic lipid peroxides, suggesting that adipose tissue mass contributes to oxidative stress.

Leptin and its metabolic interactions – an update

Obesity results from an abnormal accumulation of fat in the white adipose tissue. Recent research utilizing genetic models of obesity in rodents has implicated a major role of leptin as a controller of obesity. Leptin is a 167-amino acid peptide hormone encoded by the obesity gene (ob), which is secreted by adipocytes and plays an important role in regulating food intake, energy expenditure and adiposity. Leptin receptors (OB-R) are expressed in the central nervous system mainly in afferent satiety centres of hypothalamus and in peripheral organs such as adipose tissues, skeletal muscles, pancreatic beta-cells and liver, thus indicating the autocrine and paracrine role of leptin in energy regulation. In human beings, a highly organized circadian pattern of leptin secretion is observed with peak levels in the midnight probably resulting from cumulative hyperinsulinemia of entire day. Leptin has a dual role in weight maintenance. Leptin reflects total body adipose tissue mass whereas in conditions of negative and positive energy balance, the dynamic changes in plasma leptin concentration function as a sensor of energy balance and influence the efferent energy regulation pathways. Many effects of leptin on metabolism are mediated by interaction with Insulin and also by synergistic action with cholecystokinin. Besides physiological roles, leptin may influence pathological conditions like obesity-associated atherosclerosis, oxidative stress and cancers. The purpose of the present review is to summarize the important aspects of the biology, actions, and regulation of leptin and to serve as an update of new information.

Predicting Total and Regional Adipose Tissue Mass by B-mode Ultrasound in Japanese Prepubertal Boys

Predicting Total and Regional Adipose Tissue Mass by B-mode Ultrasound in Japanese Prepubertal Boys

Serum Leptin, Resistin, and Lipid Levels in Patients with End Stage Renal Failure with Regard to Dialysis Modality

Little information is available on the relationship between serum resistin levels and other adipokines with serum lipid levels and insulin resistance in uremic patients under different dialysis modalities. Methods. This study investigated the effects of dialysis modality on serum leptin, adiponectin, resistin, interleukin 6 (IL-6), and tumor necrosis factor (TNF) α levels in age, sex, and total adipose tissue mass (TATM); matched 30 hemodialysis (HD) patients, 30 continuous peritoneal dialysis (CAPD) patients, and 30 healthy controls; and evaluated the relationship between these adipokines and dyslipidemia and insulin resistance. Results. Serum resistin, adiponectin, IL-6, TNF-α, and high sensitive C reactive protein (hsCRP) levels were significantly increased in dialysis patients compared to controls (p < 0.05). In CAPD patients, serum leptin, resistin, triglycerides, and total cholesterol levels were higher than those in HD patients (p < 0.05). Leptin levels were positively correlated with TATM, serum triglycerides, total cholesterol, and low density lipoprotein (LDLc) levels in both dialysis groups. Resistin levels were found to positively correlate with TATM and triglycerides in CAPD patients. No relationship was found between the homeostasis model assessment-insulin resistance index (HOMA-IR) and adipokines studied. Conclusion. Serum leptin, resistin, triglycerides, and total cholesterol levels were higher in CAPD patients. Leptin levels were positively correlated with TATM, serum triglycerides, total cholesterol, and LDLc levels in dialysis patients. Resistin levels were positively correlated with TATM and triglycerides in CAPD patients. Glucose load during CAPD may be an important factor in increased in leptin, resistin, triglycerides, and total cholesterol levels in CAPD patients. These results highlight the importance of leptin and resistin as determinants of dyslipidemia, especially in CAPD patients.

Metabolic consequences of body size and body composition in hemodialysis patients

Small body mass index is associated with increased mortality in chronic hemodialysis patients. The reasons for this observation are unclear but may be related to body composition. This study aimed to investigate the body composition in chronic hemodialysis patients. The difference between body mass and the sum of muscle, bone, subcutaneous, and visceral adipose tissue masses, measured by whole body magnetic resonance imaging, was defined as the high metabolic rate compartment representing the visceral mass. Protein catabolic rate was calculated from urea kinetics. Forty chronic hemodialysis patients (mean age 54.7 years; 87.5% African Americans; 45% females) were studied. High metabolic rate compartment expressed in percent of body weight was inversely related to body weight (r=-0.475; P=0.002) and body mass index (r=-0.530; P<0.001). In a multiple linear regression model, protein catabolic rate was significantly correlated only with high metabolic rate compartment (r=0.616; P<0.001). Assuming that protein catabolic rate in addition to protein intake reflects urea and uremic toxin generation, it follows that high metabolic rate compartment is the major compartment involved in their generation. Consequently, uremic toxin production rate may be relatively higher in patients with low body weight and low body mass index as compared to their heavier counterparts. The poorer survival observed in smaller dialysis patients may be related to these relative differences.

Point: Visceral Adiposity Is Causally Related to Insulin Resistance

The relationship between obesity and insulin resistance, while well recognized for many years, has nonetheless been confusing since not all obese individuals have insulin resistance (1) and because insulin resistance occurs in individuals who have BMIs that are within the normal or mildly overweight categories (2). Early attempts to understand the relationships between obesity, type 2 diabetes, and cardiovascular disease focused on the waist-to-hip ratio as a means of distinguishing those individuals who were at increased risk from those who were not (3,4). A high waist-to-hip ratio is a surrogate for masculine distribution of obesity (central obesity). Cross-sectional studies by Kissebah et al. (5) and Krotkiewski et al. (6) in the 1980s demonstrated that hypertension, hypertriglyceridemia, hyperinsulinemia, and glucose intolerance were increased in subjects with a high waist-to-hip ratio. Long-term longitudinal population-based studies of men (13.5 years) and women (12 years) in Gothenburg, Sweden, showed that the waist-to-hip ratio was a predictor of the future development of diabetes, myocardial infarction, angina pectoris, stroke, and death independent of BMI (3,4). Technology developed in the 1990s, including computer tomography scans and MRI, made it possible to precisely measure specific adipose tissue depots such as total body adipose tissue mass, abdominal subcutaneous adipose tissue mass, visceral adipose tissue mass, and hepatic and intramuscular triglyceride content (7,8). Utilizing those techniques, many studies have examined the relationship between total adipose tissue, abdominal subcutaneous adipose tissue, and visceral adipose tissue mass and insulin resistance, the components of the metabolic syndrome, and the development of type 2 diabetes or clinical cardiovascular events (9–21). Despite the much smaller size of the visceral adipose tissue depot compared with the total subcutaneous adipose tissue depot or total adiposity, many investigations demonstrated that the visceral adipose tissue mass and not …

382 Adipose Tissue Quantity and Distribution in Healthy Term Infants Using Magnetic Resonance Imaging

Until recently lean mass and adipose tissue mass in infants and adults have been estimated by indirect methods. The use of magnetic resonance imaging has allowed direct measurement of these two components. There are no published data on normal values of adipose tissue and lean body mass in healthy term infants at birth using this technique. We carried out whole body adipose tissue (AT) magnetic resonance imaging. Individual volumes of subcutaneous, intra-abdominal and other internal adipose tissue were quantified and these summated to derive total AT. We converted total AT volume to adipose tissue mass and subtracted this from the body weight to derive the lean body mass. We expressed lean mass as a ratio of adipose tissue mass. Total adipose tissue mass is expressed as a percentage of body weight (%ATM) and the individual compartments of adipose tissue as a percentage of total adipose tissue volume. The local research ethics committee approved the study and written parental consent was sought. Results are expressed as mean (sd). 20 healthy appropriately grown Caucasian infants were studied within a week of birth. Their gestational age at birth was 39.9 (1.4) weeks. The %ATM in this group was 17.7 (2.6). Of the total adipose tissue, 91.9 (1.2) % was in the subcutaneous compartment and 3.1 (0.5) % was deposited intra abdominally. The lean to adipose tissue mass ratio was 4.8 (0.9). No significant differences were noted between male and female babies in any of the results. Normative data on body composition in the term infant has relied on data obtained either by whole body chemical analysis carried or derived from indirect measures of lean mass and fat mass. We have presented data from normal healthy term infants of similar ethnic origin using a novel technique to study body composition.

Body fat redistribution after weight gain in women with anorexia nervosa 1–3

Body image distortions are a core feature of anorexia nervosa (AN). Increasing evidence suggests that the fat distribution immediately after weight restoration in patients with AN differs from the distribution typical of healthy adult women. The purpose of this study was to assess body fat distribution before and shortly after normalization of weight in women with AN. Body composition and fat distribution were assessed by anthropometry, dual-energy X-ray absorptiometry, and whole-body magnetic resonance imaging in 29 women with AN before and after weight normalization and at a single time point in 15 female control subjects. Hormone concentrations were also evaluated in patients and control subjects. During approximately 10.1 +/- 2.9 wk (range: 4-17.3 wk) of treatment, patients with AN gained 12.2 +/- 3.6 kg, and refed weight (54.1 +/- 4.2 kg) did not differ significantly from that of control subjects (54.7 +/- 4.4 kg). Waist-to-hip circumference ratio (P < 0.006), total trunk fat (P < 0.003), visceral adipose tissue (P < 0.006), and intramuscular adipose tissue (P < 0.003) were significantly greater in the weight-recovered patients than in the control subjects. In contrast, after refeeding, total subcutaneous adipose tissue and skeletal muscle mass did not differ significantly between the patients and control subjects. In patients with AN, serum cortisol decreased and serum estradiol increased significantly with refeeding but not to control concentrations. In women with AN, normalization of weight in the short term is associated with an abnormal distribution of body fat. The implications of these findings for the long-term psychological and physical health of women with AN are unknown.

Mechanisms of Disease: adipocytokines and visceral adipose tissue—emerging role in intestinal and mesenteric diseases

Adipose tissue has long been regarded as a passive type of connective tissue that stores energy as triglycerides and releases energy as free fatty acids, however, this point of view has now changed. The wide variety of products expressed and secreted by adipose tissue, such as adiponectin, leptin, and resistin, mean that the total adipose tissue mass can be defined as a real endocrine organ. The anatomic, metabolic and biochemical characteristics of visceral adipose tissue make it interesting in the context of intestinal and mesenteric diseases. These characteristics include increased lipolysis, venous drainage via the portal vein and local glucocorticoid excess owing to the specific expression of 11-beta-hydroxysteroid-dehydrogenase type 1. In this review, the role of the visceral adipose tissue and its secretory products in intestinal and mesenteric diseases is systematically reviewed, with special focus on 'creeping fat' in Crohn's disease and mesenteric panniculitis.

Association of adiponectin and resistin with adipose tissue compartments, insulin resistance and dyslipidaemia

In this study, we investigated the association of plasma adiponectin and resistin concentrations with adipose tissue compartments in 41 free-living men with a wide range of body mass index (22-35 kg/m(2)). Using enzyme immunoassays, plasma adiponectin and resistin were measured. Intraperitoneal, retroperitoneal, subcutaneous abdominal and posterior subcutaneous abdominal adipose tissue masses (IPATM, RPATM, SAATM and PSAATM, respectively) were determined using magnetic resonance imaging. Total adipose tissue mass (TATM) was measured using bioelectrical impedance. Insulin resistance was estimated with the help of homeostasis model assessment (HOMA) score. In univariate regression, plasma adiponectin levels were inversely related to IPATM (r = -0.389, p < 0.05), SAATM (r = -0.500, p < 0.001), PSAATM (r = -0.502, p < 0.001), anterior SAATM (r = -0.422, p < 0.01) and TATM (r = -0.421, p < 0.01). In multiple regression models, adiponectin was chiefly correlated with PSAATM. Plasma adiponectin concentrations were also inversely correlated with HOMA score (r = -0.540, p < 0.001) and triglyceride (r = -0.632, p < 0.001), and positively correlated with high-density lipoprotein cholesterol (r = 0.508, p < 0.001). There were no significant correlations between resistin levels and adipose tissue masses, insulin resistance or dyslipidaemia. In men, total body fat is significantly correlated with plasma adiponectin, but not with plasma resistin levels. Low plasma adiponectin levels appear to be chiefly determined by the accumulation of posterior subcutaneous abdominal fat mass, as opposed to intra-abdominal fat, and are strongly predictive of insulin resistance and dyslipidaemia.

Acute third ventricular administration of leptin decreases protein and fat in self-selecting rats

The peripheral administration of leptin reduces food intake (FI) body weight gain (BWG) and modifies food choice. The aim of this study was to examine the effect of acute cerebral injections of leptin on food selection in rats. Male rats were first adapted to the food choice paradigm (protein, carbohydrate, fat) for 3 weeks. They were then implanted with a cannula in the third ventricle. Leptin (leptin group = L) or saline (control group = C) injections were performed at either the beginning or the end of the night at 4-day intervals. FI was recorded continuously, 3 days before, during and then after injections. Rats were sacrificed 86 h after the second injection. After both injections, BWG and FI were reduced. The reduction in FI concerned only nocturnal intake, whatever the timing of the injection. When the injection was given at the beginning of the night, the reductions after a 1-h latency period were −45% and −27.5% during the first and second days, respectively. Following the second injection, the same effects were observed immediately (−16% and −41%, respectively). Only the fat and protein intakes were significantly reduced. This lower FI was due to a reduction in meal size and duration. The reduction resulted in a lower BWG and total white adipose tissue mass. At the time of sacrifice, 6 h after food deprivation, leptinemia and insulinemia were reduced in leptin-treated rats. Glycemia values were identical. It was thus demonstrated that central leptin was a satiation factor rather than a satiety factor.

The Effects of Hypothyroidism in Rats on Serum Leptin Concentrations and Leptin mRNA Levels in Adipose Tissue and Relationship with Body Fat Composition

Both thyroid hormones and leptin affect sympathetic nervous system activity, basal metabolic rate, body fat mass, food intake, and thermogenesis, and each one also affects the actions of the other. We examined the alterations in serum leptin concentrations and leptin mRNA expression in hypothyroid rats and investigated the relation between serum leptin and leptin mRNA levels with the total adipose tissue mass and total body weight. Twenty male Wistar rats were divided into 2 groups, euthyroid and hypothyroid. Their body compositions were examined by Dual Energy X‐ray Absorptiometry at the beginning and end of the study. Serum leptin concentrations and levels of leptin mRNA in the retroperitoneal white adipose tissue were measured at the end of the study. Serum leptin concentrations did not show any difference between the two groups (1.9 ± 0.2 ng/ml in the hypo and euthyroid group, P > 0.05), but the fat mass of the hypothyroid rats were lower than the euthyroid rats (21.1 ± 2.5 g in the euthyroid group and 14.2 ± 1.9 g in the hypothyroid group, P > 0.05 between groups at the end of the study) although the difference between the groups was statistically not significant. Leptin mRNA level was significantly higher in the hypothyroid group than in the euthyroid group (21.6 ± 1.6 vs. 15.1 ± 1.2 ng respectively, P = 0.002) although the dissected retroperitoneal fat weight was significantly lower in the hypothyroid group versus the euthyroid group (1.0 ± 0.2 vs. 1.8 ± 0.2 g respectively, P = 0.013). In conclusion, the change of leptin mRNA expression in white adipocytes was thought to be the direct result of hypothyroidism or a compensatory response to metabolic changes caused by hypothyroidism.

Adipose tissue compartments and insulin resistance in overweight-obese Caucasian men

We examined the association between insulin resistance and adipose tissue compartments in overweight/obese men. Total intra-abdominal, intraperitoneal, retroperitoneal, total subcutaneous, anterior subcutaneous and posterior subcutaneous abdominal adipose tissue (PSAAT) masses (total intra-abdominal fat TIAATM, IPATM, RPATM, TSAATM, ASAATM and PSAATM, respectively) were quantified in 51 overweight/obese men using magnetic resonance imaging (MRI). Total adipose tissue mass (TATM) was also determined using bioelectrical impedance. Insulin resistance was estimated by homeostasis model assessment (HOMA) score. In univariate regression analysis, all fat compartments, with the exception of RPATM, were significantly and positively correlated with the HOMA score. The positive correlation between HOMA score and both IPATM and anterior subcutaneous adipose tissue mass was independent of obesity status. After adjusting total for TATM, only IPATM was significantly correlated with HOMA score (partial r=0.38, P<0.01). In stepwise regression, IPATM was the best predictor of HOMA score. In multivariate regression models including age, obesity status, non-esterified fatty acid (NEFAs) levels, triglycerides and energy expenditure, IPATM remained a significant positive predictor ( P<0.05) of HOMA score. In overweight/obese men intraperitoneal AT is the fat compartment that best predicts the degree of insulin resistance. This association appears to be independent of age, total body fat mass and obesity status.

Impact of blood pressure and insulin on the relationship between body fat and left ventricular structure.

Obesity leads to hypertension and metabolic disturbances, as well as left ventricular hypertrophy and altered left ventricular geometry. However, the underlying mechanisms behind these relationships are not clear. The aim of this study was to investigate how body composition, blood pressure and metabolic factors relate to left ventricular mass and geometry. We included 60 patients with obesity (BMI 31-52) and 43 non-obese subjects (BMI 18-27). Body weight, blood pressure and metabolic parameters were measured and echocardiography was performed. Body composition was determined by gender-specific anthropometric equations. Multivariate analyses showed that both body fat and lean body mass were independently and positively associated with left ventricular mass, whereas adipose tissue alone was related to relative wall thickness. When blood pressure was added to the model, the associations between body fat and left ventricular mass and geometry were weakened. Further adjustment for insulin levels eliminated the relationship between adipose tissue and relative wall thickness. Both total adipose tissue and lean body mass predict an increase in myocardial mass, while adipose tissue alone is related to a rise in relative wall thickness. The concentric left ventricular geometry associated with body fat accumulation appears to be mediated, at least in part, by blood pressure and insulin levels.

Fat compartments and apolipoprotein B-100 kinetics in overweight-obese men.

To examine the association between the kinetics of very-low-density-lipoprotein (VLDL)-apolipoprotein B-100 (apoB) and intraperitoneal, retroperitoneal, subcutaneous abdominal, and total adipose tissue masses (IPATM, RPATM, SAATM, and TATM, respectively) in overweight/obese men. Hepatic secretion of VLDL was measured using an intravenous infusion of 1-[(13)C]-leucine in 51 men with a wide range of body mass index (25.1 to 42.2 kg/m(2)). Isotopic enrichment of VLDL-apoB was measured using gas chromatography-mass spectrometry and a multicompartmental model used to estimate VLDL-apoB metabolic parameters. IPATM, RPATM, and SAATM (kilograms) were quantified between T11 and S1 using magnetic resonance imaging; TATM (kilograms) was determined using bioelectrical impedance. Insulin resistance was estimated by homeostasis model assessment (HOMA) score. In stepwise regression, IPATM was the best predictor of hepatic secretion of VLDL-apoB (r = 0.390, p < 0.005) and TATM was the best predictor of VLDL-apoB fractional catabolic rate (r = 0.282, p < 0.05). IPATM remained significantly associated with VLDL-apoB secretion after adjusting for TATM or HOMA score (r = 0.360, p < 0.01 and r = 0.310, p < 0.05, respectively). This association was also independent of age, dietary intake, and body mass index. None of the fat compartments were significantly associated with the fractional catabolic rate of VLDL-apoB after adjusting for HOMA score. In overweight/obese men, the quantity of both IPATM and TATM determine the kinetics of VLDL-apoB. The effect of IPATM on VLDL-apoB secretion is independent of both total fat mass and the degree of insulin resistance.

Sexual dimorphism in circulating leptin concentrations is not accounted for by differences in adipose tissue distribution.

Circulating concentrations of leptin normalized to total adipose tissue mass are significantly greater in females than in males. Rates of leptin expression (per gram of adipose tissue) are significantly greater in subcutaneous (SAT) than visceral (VAT) adipose tissue and the relative amount of fat stored as SAT vs VAT is significantly greater in pre-menopausal females than in males. Gender-related differences in the relative amounts of SAT and VAT may account for the greater circulating leptin concentration relative to fat-mass in females than males. We examined body composition and anatomic fat distribution by dual energy X-ray-absorptiometry (DEXA) and magnetic resonance imaging (MRI), and post-absorptive circulating concentrations of leptin and insulin in 58 subjects (26 females, 32 males). Stepwise multiple linear regression analyses, treating gender as a dichotomous variable, were performed to determine inter-relationships among leptin concentrations and insulin concentrations, VAT and SAT. Body composition by DEXA and MRI were highly correlated (r(2)=0.97, P<0.0001). There were significant gender effects on leptin/total fat mass (males, 0.17+/-0.01 ng/ml/kg; females, 0.49+/-0.05 ng/ml/kg; P<0.0001) and relative amounts of fat in SAT and VAT depots (ratio of SAT/VAT; males, 12.3+/-1.5; females, 32.9+/-3.2; P<0.0001). Circulating leptin concentration was significantly correlated with insulin concentration (P=0.001), SAT (P<0.0001) and gender (P=0.033). Circulating concentrations of insulin were significantly correlated with VAT, but not SAT, in males and with SAT, but not VAT, in females. The sexual dimorphism in the relationship between leptin and adipose tissue mass cannot be explained by differences in the relative amounts of VAT and SAT. Thus, the sexual dimorphism in plasma leptin concentration appears to reflect, at least in part, effects of circulating concentrations of gonadal steroids (especially androgens) and/or primary genetic differences that are independent of amounts of VAT or SAT.

Cardiovascular disease and risk factors in adults with hypopituitarism.

In 1992, Cuneo et al. (1992) reviewed, in this journal, the consequences of growth (GH) deficiency during adult life and coined the term ‘Growth hormone deficiency (GHD) syndrome in adults’. Limited information was available then on cardiovascular disease and risk factors in adults with hypopituitarism. More data have been published since on cardiovascular morbidity in symptom-free hypopituitary adults. Several groups have also published results on the effects of GH therapy on cardiac structure and function and on the cardiovascular risk factors. We shall review here the epidemiological and experimental data on cardiovascular morbidity and mortality in adult hypopituitarism. We shall also examine the prevalence of cardiovascular risk factors in this group of patients and their potential causes focusing on the possible role of GH deficiency and the effects of GH replacement.

Effect of regional fat distribution and Prader-Willi syndrome on plasma leptin levels.

Variability in the relationship of plasma leptin level to body mass index (BMI) could be caused by imperfect estimation of adipose mass by the BMI, heterogeneity in the pathogenesis of obesity in mixed subject groups, or variation in adipose tissue distribution. To investigate these possibilities, we examined the correlation of plasma leptin and BMI in an ethnically mixed population, a group of subjects with the Prader-Willi syndrome, and a group of Japanese-American subjects who underwent computerized tomographic measurement of adipose tissue cross-sectional areas. Highly significant and indistinguishable linear relationships between plasma leptin levels and BMI were found in the three study groups. Intersubject variability was also similar in the three groups and was reduced only when more accurate techniques for assessing adipose tissue mass were substituted for the BMI. The plasma leptin level of Japanese-American subjects in the highest quartile of intraabdominal fat area (mean area = 154.5 +/- 38.4 cm2) was 12.5 +/- 8.7 ng/mL as compared to 12.3 +/- 9.6 ng/mL (P = 0.91) for subjects in the lowest quartile of intraabdominal fat area (mean area = 51.2 +/- 20.1 cm2, P < 0.001 for difference in fat areas). We conclude that the circulating leptin level reflects total adipose tissue mass rather than a combination of adipose tissue mass and distribution, and that the Prader-Willi syndrome does not alter the relationship between these two variables.

Obesity genes and the regulation of body fat content.

Physiological investigation has demonstrated that the central nervous system monitors body composition and adjusts energy intake and expenditure to stabilize total adipose tissue mass. Genetic variations in the signalling molecules involved in this regulatory system account for the heritable component of body fat content. The application of molecular techniques to rodent models of Mendelian obesity has resulted in the characterization of five loci at which mutations produce an abnormal accumulation of body fat. The genes at these loci include agouti, which encodes a molecule that antagonizes the binding of alpha melanocyte-stimulating hormone to its receptor; fat, which encodes carboxypeptidase E; tubby, which encodes a putative phosphodiesterase; obese, which encodes a circulating satiety protein; and diabetes, which encodes the receptor for the obese gene product. A more detailed understanding of the functional interrelationships of these genes should lead to important new insights into the causes and potential therapies for human obesity.