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Swedish obese subjects (SOS). Recruitment for an intervention study and a selected description of the obese state.

SOS (Swedish obese subjects) is an on-going intervention trial designed to determine whether the mortality and morbidity rates among obese individuals who lose weight by surgical means (gastric banding, vertical banded gastroplasty and gastric by-pass) differ from the rates associated with conventional treatment. For this purpose, the study is recruiting a sample of obese men and women who constitute a registry of potential subjects from which the participants are drawn. Eligibility criteria for participation in the registry were: age at application 37-57 years and BMI greater than or equal to 34 kg/m2 for men and greater than or equal to 38 kg/m2 for women. Before receiving a health examination, all patients complete extensive questionnaires on current and past health status, utilization of medical care and medications, socio-economic status, psychological profiles, dietary habits, physical activity, weight history, and familial disposition to obesity. Each surgical case is matched to its optimal control in the registry, to ensure that the two groups do not differ systematically with respect to any of 18 matching variables that may affect prognosis. The first 1006 subjects included in the registry have been studied with respect to morbidity and compared with on-going population studies of men and women in Göteborg, Sweden. The relative risks of prevalent disease and symptoms associated with obesity in 50-year-old males and females respectively were 4.3 and 4.7 (dyspnoea), 14.7 and 11.8 (angina), 6.3 (myocardial infarction, males only), 2.1 and 4.5 (hypertension), 5.2 and 6.6 (diabetes), 4.6 and 26.1 (claudication) and 1.7 and 1.8 (gall bladder disease). Correspondingly, obese males and females display elevations of systolic and diastolic blood pressure, fasting glucose, insulin, triglyceride, and uric acid levels. However, total cholesterol was not increased in obese males and was in fact significantly lower in obese compared with reference women. HDL-cholesterol was lower in obese than reference men (data were not available in reference women). The rate of taking sick pensions was over twice as high in SOS obese patients than in population controls. Finally, comparison of measurements with self-reported prevalence estimates revealed a considerable amount of previously undiagnosed hypertension and diabetes in the obese subjects. These data suggest that the excess health risks associated with obesity may not be fully appreciated.

Adipose Tissue↗

Onset of obesity and puberty in genetically obese SHHF/Mcc-cp rats.

SHHF/Mcc-cp rats, as a model of obesity and diabetes, were followed through breeding and throughout development to determine timing of obesity and sexual development. The obesity or corpulency gene (cp) follows recessive transmission characteristics with no segregation between sexes. Although the frequency of litter sizes was different, the mean litter size of heterozygous mating (8.9 +/- 0.3 pups/litter) was not different from homozygous lean matings (7.9 +/- 0.3 pups/litter). Body weights of the population of female obese rats statistically deviated from lean females at day 35 and obese males deviated from lean males at day 37. Vaginal opening of obese and lean females did not differ in time of occurrence (day 34.6 +/- 0.2 for lean and 33.6 +/- 0.4 for obese). To further evaluate development and examine onset of diabetes, animals were killed at six, eight and ten weeks of age and development of reproductive organs and plasma levels of insulin, glucose, and testosterone or oestradiol determined. Testes development was slightly retarded in the obese male with smaller testes at six weeks of age, however testes size increased at eight and ten weeks of age and was not significantly less than lean males. In contrast, testes function was impaired with smaller seminal vesicles and lower testosterone levels in the obese male rats. Both ovarian and uterine weights were significantly less in obese females. However, oestradiol levels were not significantly different at any of the time points examined. Development of elevated insulin levels were first noted in the obese female at six weeks of age, however marked hyperinsulinemia developed only in the obese males at ten weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Anti-obesity effect of two different levels of dehydroepiandrosterone in lean and obese middle-aged female Zucker rats.

Dehydroepiandrosterone has previously been shown to prevent weight gain in growing lean and obese mice and rats. In the present study, lean and obese female Zucker rats were treated with either 0.6 or 1.0 percent DHEA in the diet from 8 until 14 months of age. In lean rats, 0.6 percent DHEA prevented weight gain and 1.0 percent DHEA resulted in significant weight loss compared to initial body weight. Control lean rats had a significant weight gain. Both 0.6 and 1.0 percent DHEA obese rats lost weight over the experimental period while control obese rats gained weight. Food intake of DHEA-treated obese rats was lowered compared to control obese rats but was similar to that of all lean groups. DHEA lowered serum insulin levels in both lean and obese rats relative to control groups. Both 0.6 and 1.0 percent DHEA lean rats had elevated hepatic G6PD activity compared to control lean rats. DHEA obese rats had lowered G6PD activity compared to the control obese rats. Hepatic malic enzyme was elevated by DHEA treatment in both lean and obese Zucker rats. Adipose tissue weights were lowered substantially in DHEA treated lean and obese rats versus their control groups. These data indicate that DHEA treatment in adult rats has an anti-obesity effect.

Adipose Tissue↗

Many factors can affect the prevalence of hypertension in obese patients: role of cuff size and type of obesity.

OBJECTIVE: To determine to what extent methodological errors, including measurements taken with inappropriate cuffs and/or inaccuracies in patient enrollment, can contribute to overestimating the prevalence of hypertension in overweight or obese women. EXPERIMENTAL DESIGN: Randomized and comparative investigation in overweight or obese outpatient women of the Obesity Clinic, Internal Medicine Institute, Chieti University. PATIENTS: In 1,791 overweight or obese women, randomly selected and stratified by age (41-60 years), blood pressure (BP) was taken with casual measurement in the morning. The entire study group was divided into two subgroups. In the first one, causal BP was measured with a standard-size cuff (RCS), while an appropriate large-size cuff was used for the second one (LCS). Patients of the latter subgroup were also divided by type of obesity (android and gynoid), based on their waist-to-hip ratio. RESULTS: In the LCS subgroup, the hypertension prevalence rate was strikingly lower among overweight and obese women, as well as in the younger and older age groups, when compared with the corresponding RCS subgroups (p < 0.001). The hypertension prevalence rate was higher for all android obese subjects (53%), including younger (34%) and older (64%) groups, when compared with gynoid obese patients (29%, 18% and 42%, respectively). CONCLUSIONS: A comparison of different reports on the prevalence of hypertension in obesity reveals considerable differences, due mainly to age, sex, race and income level. Nevertheless, our data seem to indicate that even after adjusting for the above-mentioned variables, two significant confounding factors, cuff hypertension and the prevalence of android obesity in the obese study population, could be responsible for over-estimating the prevalence of hypertension. It should be noted that for certain groups of overweight and obese women, the prevalence of hypertension becomes similar to the rate found among the general population, as reported in many large epidemiological surveys.

Adult↗

Rates of psychiatric disorders in a clinical study group of adolescents with extreme obesity and in obese adolescents ascertained via a population based study.

OBJECTIVE: To compare rates of DSM-IV psychiatric disorders between (1) a clinical study group of extremely obese adolescents and young adults, (2) gender-matched population-based obese controls and (3) a population-based control group of the same age range. DESIGN: Rates of psychiatric disorders were assessed in (1) the clinical study group of obese adolescents and (2) the population based sample of obese adolescents, and compared to (3) a large population-based control group using a standardized psychiatric interview. SUBJECTS: (1) Clinical study group: 30 female and 17 male extremely obese adolescents and young adults (age range: 15-21 y; mean BMI:42.4 kg/m2). (2) Thirty females and 17 males with the highest BMI (age range 15-21 y; mean BMI: 29.8 kg/m2) of a population-based control group encompassing 1655 (805 males) adolescents and young adults. (3) The population based control group excluding the 30 females and 17 males with the highest BMI (n = 1608; 788 males). MEASUREMENTS: Munich-Composite International Diagnostic Interview (M-CIDI) allowing for DSM-IV diagnoses. RESULTS: High rates of mood, anxiety, somatoform and eating disorders were detected in the clinical sample of obese adolescents which exceeded those observed in population controls (all P-values < 0.01). Rates between population-based obese adolescents and young adults and population controls did not differ. In most patients the psychiatric disorders set in after onset of obesity. 57% and 35% of the female and male patients, respectively, reported eating binges with lack of control. However, less than one-half of these patients qualified for a DSM-IV diagnosis of an eating disorder. CONCLUSIONS: Extremely obese adolescents and young adults who seek long-term inpatient treatment have a high lifetime prevalence for affective, anxiety, somatoform and eating disorders. Because the mean BMI of the clinical study group was considerably higher than that of the obese population controls, we were not able to clarify whether the high rate of psychopathology in the study group was related to the extreme obesity or to their treatment-seeking behavior.

Adipose Tissue↗

Obstetric outcomes after in vitro fertilization in obese and morbidly obese women.

OBJECTIVE: In addition to numerous health detriments caused by obesity, fertility and pregnancy success may also be compromised. The aims of this study were to compare the effects of obesity and morbid obesity on in vitro fertilization (IVF) outcomes. We also investigated the effects of obesity on obstetric outcomes after IVF treatment. METHODS: Retrospective study of women less than 38 years of age during their first fresh IVF cycle (January 1995 to April 2005). RESULTS: A total of 1,293 women were included in the study, with 236 obese women (body mass index [BMI] = 30-39.9) and 79 morbidly obese women (BMI > or = 40). The morbidly obese group had a 25.3% IVF cycle cancellation rate compared with 10.9% in normal-weight women (odds ratio 2.73, 95% confidence interval 1.49-5.0), P < .001). Morbidly obese women without polycystic ovarian syndrome had an even higher cancellation rate (33%). Women with higher BMI required significantly more days of gonadotropin stimulation but had lower peak estradiol levels (P < .001). There were no significant differences in clinical pregnancy or delivery rates between the four BMI groups. Of the women who delivered, there was a significant linear trend for risk of preeclampsia, gestational diabetes, and cesarean delivery with increasing BMI (P < .03). CONCLUSION: We report a significantly higher risk for IVF cycle cancellation in morbidly obese patients with no effect of BMI on clinical pregnancy or delivery rate. However, obese and morbidly obese subjects had a significantly higher risk for obstetric complications. This target population should be aggressively counseled regarding their increased obstetric risk and offered treatment options for weight reduction before the initiation of fertility therapy. LEVEL OF EVIDENCE: II-2.

Adult↗

Effect of obesity and morbid obesity on the growth hormone (GH) secretion elicited by the combined GHRH + GHRP-6 test.

OBJECTIVE: Obesity is characterized by low basal levels of growth hormone (GH) and impeded GH release. However, the main problem arises in the diagnosis of GH deficiency in adults, as all accepted cut-offs in the diagnostic tests of GH reserve are no longer valid in obese subjects. In this work, the role of obesity in the GH response elicited by the GHRH + GHRP-6 test was assessed in a large population of obese and nonobese subjects. PATIENTS: GHRH + GHRP-6-induced GH peaks were evaluated in 542 subjects. One hundred and five were healthy obese, 50 were morbid obese, and 261 were nonobese (both normal weight and overweight). One hundred and seventy-six GH-deficient patients (obese and nonobese) were also studied. RESULTS: A regression analysis of the 366 subjects with normal pituitary function indicated that adiposity had a negative effect on the elicited GH peak (r = -0.503, P < 0.0001). A receiver operating characteristic (ROC) curve analysis showed that in subjects with a BMI < or =35, the currently accepted cut-offs of the GHRH + GHRP-6 test (GH peaks > or =20 microg/l: normal secretion; GH peaks < or =10 microg/l: GH deficiency), were fully operative. However, in subjects with a BMI > 35, normality was indicated by GH peaks > or =15 microg/l and GH deficiency by peaks < or =5 microg/l (1 microg/l = 2.6 mU/l). CONCLUSIONS: This study confirms: (a) that the combined provocative test is adequate to separate normal and GH-deficient subjects; (b) the negative effect of obesity on GH secretion; (c) that obesity accounts for 25% of the reduction of GH release; and (d) that present cut-off values are applicable to normal weight, overweight and grade I obesity subjects, whereas in obese subjects with a BMI exceeding 35, all the normative limits of the GHRH-GHRP +6 test must be reduced by 5 microg/l.

Adolescent↗

Insulin levels, physical activity, and urinary catecholamine excretion of obese and non-obese rhesus monkeys.

The hypothesis that spontaneous obesity in rhesus monkeys is associated with abnormalities in energy expenditure was tested. Obese (n=7) and non-obese (n=5) monkeys were described in terms of body size and composition, food intake, and physical activity. Additionally, the relationships among fasting and stimulated insulin levels in serum, C-peptide levels in serum and urine, and urinary catecholamines were examined. Obese animals had primarily abdominal deposition of excess body fat, as indicated by markedly elevated abdominal circumferences and skin-fold thicknesses. Food intake did not differ between groups. Physical activity was much lower in the obese group. Obese monkeys had markedly higher serum insulin and C-peptide levels in the fasted state and in response to an intravenous glucose challenge. Urinary excretion of C-peptide and catecholamines was measured during successive 2-day periods of ad libitum feeding, food deprivation, and refeeding in order to examine potential differences between groups in sympathoadrenal activity and their relationship to insulin secretion. C-peptide excretion was greater for obese and decreased for both groups during food deprivation. Urinary dopamine (DA), norepinephrine (NE), and epinephrine (E) levels were significantly greater for obese animals in all conditions. DA excretion was lowest during deprivation and E excretion was lowest during refeeding, whereas NE excretion was relatively unaffected by feeding condition. The overall patterns of C-peptide and catecholamine excretion were qualitatively similar for both groups, and there were no reliable differences between obese and non-obese in their responses to the feeding manipulation. The results suggest that hyperinsulinemia associated with obesity in rhesus monkeys is linked to increased catecholamine secretion and a resistance to catecholaminergic action.

Adrenal Glands↗

Microarray profiling of isolated abdominal subcutaneous adipocytes from obese vs non-obese Pima Indians: increased expression of inflammation-related genes.

AIMS/HYPOTHESIS: Obesity increases the risk of developing major diseases such as diabetes and cardiovascular disease. Adipose tissue, particularly adipocytes, may play a major role in the development of obesity and its comorbidities. The aim of this study was to characterise, in adipocytes from obese people, the most differentially expressed genes that might be relevant to the development of obesity. METHODS: We carried out microarray gene profiling of isolated abdominal subcutaneous adipocytes from 20 non-obese (BMI 25+/-3 kg/m2) and 19 obese (BMI 55+/-8 kg/m2) non-diabetic Pima Indians using Affymetrix HG-U95 GeneChip arrays. After data analyses, we measured the transcript levels of selected genes based on their biological functions and chromosomal positions using quantitative real-time PCR. RESULTS: The most differentially expressed genes in adipocytes of obese individuals consisted of 433 upregulated and 244 downregulated genes. Of these, 410 genes could be classified into 20 functional Gene Ontology categories. The analyses indicated that the inflammation/immune response category was over-represented, and that most inflammation-related genes were upregulated in adipocytes of obese subjects. Quantitative real-time PCR confirmed the transcriptional upregulation of representative inflammation-related genes (CCL2 and CCL3) encoding the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein 1alpha. The differential expression levels of eight positional candidate genes, including inflammation-related THY1 and C1QTNF5, were also confirmed. These genes are located on chromosome 11q22-q24, a region with linkage to obesity in the Pima Indians. CONCLUSIONS/INTERPRETATION: This study provides evidence supporting the active role of mature adipocytes in obesity-related inflammation. It also provides potential candidate genes for susceptibility to obesity.

Abdomen↗

Differential effect of insulin on whole-body proteolysis and glucose metabolism in normal-weight, obese, and reduced-obese women.

The whole-body rate of proteolysis, as indicated by the postabsorptive appearance rate (Ra) of leucine, is increased in obese women. The present study was conducted to examine the hypothesis that the increased proteolysis is explained by insulin resistance, and to determine if proteolysis returns to normal when obese women reduce to normal weight. The mean basal leucine Ra was 21% higher in 31 obese women (> 135% ideal weight) than in 17 normal-weight women, and 9% higher per kilogram lean body mass ([LBM] P > .05). When 17 of the obese women reduced and stabilized at 100% to 116% of ideal weight, their mean basal leucine Ra decreased 17% (7%/kg LBM) and was not significantly different from that of the normal-weight control group. Insulin (40 mU/m2/min) was infused for 2 hours while maintaining euglycemia in eight normal-weight, 14 obese, and eight reduced-obese subjects. Glucose disposal per kilogram LBM was 29% lower in obese than in normal-weight subjects (P < .05) and was normal in the reduced-obese subjects. Insulin suppressed the leucine Ra an average of 18.4% in the control group, 20.4% in the obese group, and 24.1% in the reduced-obese group. Suppression of the leucine Ra by insulin did not correlate with the waist to hip ratio (WHR), glucose disposal rate, or basal leucine Ra. We conclude that the increased basal proteolysis of obese women is reversed by weight loss, and is not caused by insulin resistance.

Adult↗

Beta(3)-adrenergic receptor gene variant is associated with upper body obesity only in obese Japanese-American men but not in women.

We investigated gender differences in the relationships between the Trp64Arg variant of the beta(3)-adrenergic receptor (AR) gene in obesity and insulin resistance in nondiabetic subjects. In 476 nondiabetic Japanese-Americans (M/F=204/272), the Trp64Arg variant of the beta(3)-AR gene was examined. The presence or absence of the Trp64Arg mutation was examined in DNA separated from leukocytes in peripheral blood using the PCR-RFLP method. The frequency of abnormal allele of the beta(3)-AR gene was 0.18 for males and 0.17 for females, almost the same as the reported values in Japanese. There was no difference in the frequency of the beta(3)-AR gene variant between obese and non obese subjects for each gender. However, among obese males (body mass index > or =24.2 kg/m(2)), with the beta(3)-AR gene mutation, the waist-to-hip ratio, fasting insulin, 2-h insulin, total insulin, and HOMA, an index of insulin resistance, were all significantly higher than obese males without the mutation. In females, the index of obesity, insulin resistance, or lipid metabolism did not differ significantly between the subjects with or without the beta(3)-AR gene variant either in the obese and non-obese group. We suggest that the beta(3)-AR gene variant is not important as an obesity-inducing factor in Japanese. However, in males, when obesity becomes obvious, the beta(3)-AR gene variant is considered to influence the enhancement of insulin resistance, in association with visceral obesity.

Aged↗

Musculoskeletal pain in the obese: a comparison with a general population and long-term changes after conventional and surgical obesity treatment.

Obesity is associated with musculoskeletal pain and osteoarthritis. This study compares the prevalence of work-restricting musculoskeletal pain in an obese and a general population and investigates changes in the incidence of and recovery from musculoskeletal pain after bariatric surgery or conventional obesity treatment. A random sample of 1135 subjects from a general population was compared with 6328 obese subjects in the Swedish obese subjects (SOS) study. For the obese subjects, information about musculoskeletal pain was also collected 2 and 6 years after obesity surgery or the start of non-surgical treatment. In both sexes, self-reported work-restricting pain in the neck and back area and in the hip, knee and ankle joints was more common in the obese subjects than in the general population (odds ratios (ORs) ranging from 1.7 to 9.9, P<0.001). Operated obese women had a lower incidence of work-restricting pain in the knee and ankle joints compared with the conventionally treated control group over 2 and 6 years (ORs 0.51-0.71). Among subjects reporting symptoms at baseline, the recovery rate for pain in the knee and ankle joints in men and pain in the neck and back and in the hip, knee and ankle joints in women improved in the surgical group compared with the control group after 2 years (ORs 1.4-4.8). Obese subjects have more problems with work-restricting musculoskeletal pain than the general population. Surgical obesity treatment reduces the long-term risk of developing work-restricting musculoskeletal pain and increases the likelihood of recovering from such pain.

Adult↗

Using obese-specific charts of height and height velocity for assessment of growth in obese children and adolescents during weight excess reduction.

OBJECTIVE: The influence of weight excess reduction on height and height velocity of obese subjects should be evaluated on the basis of appropriate standards, since the pattern of growth of obese subjects is different from that of normal weight subjects. DESIGN, SUBJECTS AND MEASUREMENTS: Height, weight and triceps skinfold thickness were recorded from 17987 school subjects (9256 males and 8731 females), 3-18 y of age, from three provinces of central Italy, and a growth reference curve of height was constructed. Using BMI (as computed using the tables of Rolland-Cachera et al) and triceps skinfold thickness, normal-weight subjects (NWS) and obese subjects (OS) were identified and specific reference curves (mean+/-s.d. every sixth month of age) were developed for both groups. Centiles of height were also calculated for OS. Various (2-4) measurements of height in school subjects were performed and a graph of height velocity (HV) was constructed in NWS and in OS using the JPPS method. The yearly mean +/-s.d. of HV was also calculated, based on square root transformed data (in order to realise a Gaussian distribution), deriving from successive measurements in total subjects, in NWS and in OS. The z-scores of height and of the square root of HV were calculated in 217 obese subjects (125 males and 92 females) before and during a weight excess reduction programme (WERP). Obese subjects in WERP who showed a reduction of z-score of BMI were considered as 'responsive'; those who either maintained or showed an increase of z-score of BMI were considered as 'non-responsive'. Obese subjects in WERP were followed for 1-4 y, giving the following results: 0-1 y, 142 responsives and 75 non-responsives; 0-2 y, 76 responsives and 33 non-responsives; 0-3 y, 35 responsives and 30 non-responsives; 0-4 y, 24 responsives and 18 non-responsives. RESULTS: Compared to NWS, OS showed a significantly greater HV in 4-9y males and in 4-8y females, but in older children the pubertal spurt was reduced and more precocious. As a result, the height of OS, which was greater in 3-13 year-old males and in 3-11.5 year-old females, subsequently showed a reduction, as compared to that of NWS, in 16-18 year-old males and in 13-18 year-old females. In both responsive and non-responsive groups of obese subjects in WERP, the z-scores of height showed a reduction during WERP when evaluated using the reference curve of the total school population. In contrast, when their growth was evaluated according to the obese-specific reference curve, no significant variation was observed comparing both z-scores before and during the WERP. CONCLUSIONS: More appropriate information on the growth of obese subjects may be obtained when evaluating the height and HV according to obese-specific reference standards from the same population of origin. Adopting this modality, no significant variation of height resulted during WERP in obese children.

Adolescent↗

Influence of duration of obesity on the insulin resistance of obese non-diabetic patients.

OBJECTIVE: To investigate whether duration of obesity has an independent impact on insulin resistance. DESIGN: Case-control study. SUBJECTS: 30 non-diabetic obese subjects (age, 34+/-12 y, body mass index (BMI), 33.5+/-0.8 kg x m[-2]) with a range (1-35 y) of self-reported duration of obesity, and 12 age- and gender-matched non-obese controls (BMI, 22.1+/-0.6 kg x m[-2]). MEASUREMENTS: Oral glucose tolerance (40 g x m[-2]), insulin sensitivity (by the euglycaemic insulin clamp technique), and insulin secretion (as the product of post-hepatic insulin clearance and plasma insulin concentration). RESULTS: The obese group presented hyperinsulinaemia in the basal state and after glucose loading (insulin area = 58+/-5 vs 33+/-3 nmol x I[-1] x 2 h, P = 0.005), insulin resistance (M value = 37.4+/-4.8 vs 50.6+/-2.6 micromol x min[-1] x kg FFM[-1], P = 0.002), and insulin hypersecretion (61.9+/-6.0 vs 33.9 +/- 4.0 nmol x 2 h, P = 0.007); endogenous glucose production was similar in the two groups. In the whole dataset, insulin resistance was directly related to BMI, the waist-to-hip ratio (WHR), endogenous glucose production, insulin secretion, and fasting serum triglycerides and uric acid concentrations. When the obese subjects were stratified by duration of obesity, insulin resistance was progressively lower with longer obesity duration (P = 0.04). When simultaneously adjusting by age, gender and BMI, obesity duration was independently associated with greater insulin sensitivity (P = 0.003), lower plasma insulin response to oral glucose (P = 0.001), and lower fasting and glucose-stimulated insulin release (P = 0.01 for both). CONCLUSIONS: In obese subjects with preserved glucose tolerance, duration of obesity is associated with better insulin sensitivity irrespective of the degree of overweight.

Adult↗

Obesity related phenotypes in families selected for extreme obesity and leanness.

BACKGROUND: Obesity is a multigenic trait, and special methods and sampling designs are needed for gene identification. OBJECTIVE: To describe characteristics of families selected to increase information for genetic linkage studies of obesity. DESIGN: Families having extremely obese siblings with a lean parent and sibling. SUBJECTS: 594 members of 94 Caucasian families. MEASUREMENTS: Measured height and weight, bioelectric impedance, skinfolds, circumferences and questionnaires. RESULTS: Families have an extreme range of obesity phenotypes, which are bimodally distributed. The obese individuals are predominantly women with an onset of obesity early in life. Obesity onset age was negatively correlated with level of obesity, and onset ages were correlated among family members. Individual obesity measures were highly correlated. The extreme range of phenotypes within families increases family variability and presumably gene segregation. CONCLUSION: Sampling families through extremely obese sibling pairs with a lean parent and sibling results in families with an extreme range of obesity and leanness. The large within-family variance and early age of onset should make these families highly informative for gene mapping and gene identification studies.

Adolescent↗

Tissue differences in the response of the pyruvate dehydrogenase complex to a glucose load during the development of obesity in gold-thioglucose-obese mice.

The activity of pyruvate dehydrogenase (PDHC), a key enzyme complex in the oxidative disposal of glucose, was measured after an oral glucose load in the heart, liver, quadriceps muscle, white adipose tissue (WAT) and brown adipose tissue (BAT) of gold-thioglucose (GTG)-obese mice at different stages during the development of obesity and in age-matched controls. Significant responses to the glucose load were seen 30 min post-gavage in heart, WAT and BAT of control mice but no change was observed in quadriceps muscle. The increase in activity of the active form of PDHC (PDHCa) in response to glucose in heart was reduced 2 weeks after the induction of GTG-obesity with no response in 5 or 10 week obese mice. A 2-3-fold increase in the PDHCa response in both WAT and BAT of 2 week obese mice was absent in 5 and 10 week obese animals. Basal PDHCa activity in quadriceps muscle was increased in 2 week obese mice but subsequently returned to control levels as obesity progressed. The glucose load produced no change in the activity of PDHCa in quadriceps muscle of obese mice. These results demonstrate that changes in the capacity for oxidative glucose disposal in different tissues, as indicated by changes in PDHCa activity, may contribute to glucose-intolerance and insulin-resistance in GTG-obese mice and that the response of the PDHC to insulin during the development of obesity varies in different tissues.

Adipose Tissue↗

Plasma acylation stimulating protein, adipsin and lipids in non-obese and obese populations.

BACKGROUND: Acylation stimulating protein (ASP) is a potent stimulator of TG synthesis in human adipocytes. DESIGN: In the present study, we have analysed plasma ASP and adipsin levels and their relationships to plasma lipids in non-obese and obese groups. RESULTS: The results show that the frequency distribution of ASP is skewed but that of adipsin is normal in both groups. In the non-obese population, the mean levels of plasma ASP and adipsin were 20.2 nmol L-1 (median) and 66.6 +/- 19 nmol L-1 (mean) respectively. No difference was observed between men and women for each of the parameters. In the obese population, the median plasma ASP was increased by 246% (69.9 nmol L-1) and adipsin by 31% (87.0 +/- 22.7 nmol L-1) above that of the control group. Although the levels for men and women were not statistically different for adipsin, the median ASP plasma concentration was 1.9-fold higher in obese women than in obese men (71.8 nmol L-1 vs. 37.6 nmol L-1, P < 0.05). Best subset regression analysis provided a model with variables that best predict plasma ASP [r2 = 0.160, P < 0.008 for body mass index (BMI), P < 0.05 for triacylglycerol (TG), P < 0.03 for free fatty acid (FFA)] and plasma adipsin (r2 = 0.057, P < 0.017 for BMI) in a non-obese population. In obese subjects, the model was different for plasma ASP (P = NS for any of the variables) and plasma adipsin (r2 = 0.356, P < 0.008 for FFA, P < 0.0002 for BMI, P < 0.02 for age). There was no correlation between ASP and adipsin in either the non-obese or the obese group. CONCLUSION: The present data suggest involvement of the ASP/adipsin pathway in the pathogenesis of obesity.

Adult↗

Criteria for medical intervention in obese children: a new definition of 'obesity disease' in Japanese children.

The Committee of the Japan Society for the Study of Obesity reported the new criteria for 'obesity disease' for Japanese adults in 2000. We defined the criteria for the diagnosis of obesity in children with medical problems, corresponding to the 'obesity disease' criteria in adults. Obesity in childhood was defined as follows: percentage of overweight (POW) and body fat exceeded the criteria. 'Obesity disease in childhood' was defined as obesity associated with health or medical problems, and with indications for medical intervention. Medical problems with indications for immediate intervention were grouped as A problems, which consisted of (i). hypertension; (ii). sleep apnea or hypoventilation; (iii). Type 2 diabetes mellitus or impaired glucose tolerance; and (iv). increased waist circumference or accumulation of visceral adipose tissue. Metabolic derangements or equivalent associated with obesity were grouped as B problems: (i). liver dysfunction; (ii). hyperinsulinemia; (iii). hypercholesterolemia; (iv). hypertriglyceridemia; (v). low serum high-density lipoprotein cholesterol; (vi). acanthosis nigricans, and (vii). hyperuricemia. Obese children over 5 years of age with following conditions were diagnosed as 'obesity disease in childhood': (i). any 'A problem', (ii) POW >or= 50% and any 'B problem', or (3) POW < 50% and more than one 'B problem' or equivalent. We decided to take physicosocial problems related to obesity into consideration as the criteria. The resultant criteria are proposed by the Committee for Research of Appropriate Body Build in Children*.

Asian People↗