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PubMed2003

[Resistine--a new hormone secreted by adipose tissue (adipose tissue in insulin resistance)].

Obesity is an important risk factor for the development of insulin resistance and type 2 diabetes. The molecular mechanism linking obesity to insulin resistance is, however, unclear. Recently, a new circulating hormone resistine, which is expressed in adipose tissue, has been identified. Resistine has been shown to antagonize insulin action. Resistine levels are increased in diet-induced obesity as well as in genetic models of obesity and insulin resistance. Furthermore, resistine gene expression is markedly downregulated by treatment with anti-diabetic drugs called thiazolidinediones, that improve target-tissue sensitivity to insulin. It has been found that in human abdominal adipose tissue, which is thought to be a main risk factor for insulin resistance, amount of resistine mRNA is higher than in other fat depots. Resistine, therefore, may play a role in the pathogenesis of obesity-related insulin resistance.

Adipose Tissue↗

PubMed2003

[Estimate of human visceral adipose area and abdominal subcutaneous adipose area in obese Chinese by simple anthropometric parameters].

OBJECTIVE: To explore the relationship of simple anthropometric parameters with abdominal subcutaneous adipose area (SA) with visceral adipose area (VA), and to generate equations predicting SA and VA by simple anthropometric parameters. METHODS: SA and VA were measured with computed tomography (CT) in 309 human subjects (male 88, female 221). Weight (W), height (H), body mass index (BMI), waist circumference (WC), abdominal circumference (AC), hip circumference (HC) and waist to hip ratio (WHR) were also measured. Multiple stepwise regression analysis was used to generate equations for predicting SA and VA from age and simple anthropometric parameters of 259 subjects (80%, including 181 women and 78 men) randomly selected from the overall sample. These equations were then cross-validated in the remaining 50 subjects (20%, including 40 women and 10 men). RESULTS: The best regression equations for male were developed for predicting SA and VA, and the explanatory variables included WC and age. In women, the equation for predicting SA included AC and BMI; the equation for predicting VA included WHR and W and age. In the cross-validation study, the differences between predicted and observed values of VA in men and women were -7.83% and -6.94%, respectively; the differences between predicted and observed values of SA in men and women were 8.01% and 0.69%, respectively. The goodness of fit between predicted and observed values is good. CONCLUSION: The absolute amount of human VA and SA in obese Chinese can be predicted from anthropometric measurements.

Abdominal Cavity↗

PubMed1989

[Behavior of back fat thickness, the activity of NADP-dependent dehydrogenases from adipose tissue and adipose tissue constituents fat and protein and their evidence for energy metabolism in dairy cows].

Studies were conducted into 60 Friesian dairy cattle in the GDR for determination of dorsal fat thickness (DFT), activities of glucose-6-phosphate dehydrogenase (GPDH) and isocitrate dehydrogenase (ICDH) in adipose tissue, concentrations of fat and protein in adipose tissue, 2 weeks ante partum as well as 0, 2, 4, 6, 8, 12, 16, 20, 28, 36 weeks post partum, and liver fat levels, 2 and 4 weeks post partum. DFT, ICDH, GPDH, ICDH-GPDH ratio, fat level, fat-protein quotient, changes in DFT, GPDH, and fat-protein quotient exhibited significant relations with the weeks of lactation. The above 60 experimental cows were subdivided by 6 groups of half-siblings consisting of 10 animals each. Significant differences were found to exist between these groups of half-siblings with regard to DFT, GPDH, ICDH-GPDH ratio, and fat-protein quotient. Within each of the half-sibling groups, significant differences were found to exist between individuals for DFT, ICDH, GPDH, ICDH-GPDH ratio, and fat-protein quotient. The above parameters can be used to describe the energy metabolism of dairy cow via quantitative and temporal curves of fat mobilisation and fat deposition. In the context of both animal health and breeding, more attention should be given to determination of mobilisation and deposition of fat as well as to the post partum energy deficit.

Adipose Tissue↗

PubMed1989

Adiposity and adipose tissue distribution in relation to incidence of diabetes in women: results from a prospective population study in Gothenburg, Sweden.

The results refer to a 12-year longitudinal population study of women in Gothenburg, Sweden. Correlations were studied between initial adipose tissue amount and adipose tissue distribution on the one hand and incidence of diabetes and change in serum blood glucose concentration on the other. Body mass index, sum of two skinfolds and waist-to-hip circumference ratio were significantly associated with incidence of diabetes. The waist-to-hip ratio was also positively associated with an increase of serum glucose concentration in the fasting state during the followup period. The significant correlations remained in multivariate analysis and were independent of age, initial smoking habits, systolic blood pressure, intake of antihypertensive drugs and serum cholesterol, triglyceride and glucose concentrations. The correlations between the separate anthropometric variables and incidence of diabetes remained when the other anthropometric variables were considered as background factors. The distribution of fat to the abdominal region as well as the total amount of fat per se seem to be important risk factors for diabetes and the effect of one of these factors seems to add to the other.

Adipose Tissue↗

PubMed1977

Adiposity and the pharmacokinetics of halothane. The effect of adiposity on the maintenance of and recovery from halothane anaesthesia.

Thirty fit patients (15-70 years, 46-98 kg) undergoing body-surface operations were selected to include a wide range of adiposity (12-45% of total body weight estimated from measurements of skinfold thickness). They were anaesthetized with halothane and 70% N2O in O2. From measurements of total ventilation (ml min-1 kg-1) and of halothane concentrations in inspired (F1) end-tidal (FE') and 'mixed-spill' (FS) gases, the following parameters were calculated for 5-min intervals from 20 to 40 min after induction; the rate of uptake of halothane per percent inspired concentration (Vha1 ml min-1%-1) and the degree of equilibrium achieved with the inspired concentration, calculated as FE'/F1 expressed as a percentage. Multiple-regression analysis of the results for 19 patients, taking account of the effects of body fat, ventilation, age, and the blood-gas partition coefficient lambda of halothane for the individual patient, showed that Vha1 increased with adiposity (b=0-375, P=0-0019), and with ventilation (b=0-054, P=0-09) but decreased with increasing age (b=-0-258, P=0-006). The time intervals between the end of the anaesthetic and the achievement of four defined levels of recovery (response to painful stimulus obedience to a simple command, response to a question, orientation in time and space), were recorded. Multiple-regression analysis showed that recovery time increased with addiposity, duration of administration and end-tidal concentration at the end of the administration, and decreased with increasing age. All four effects were statistically non-significant at the first levels of recovery but all increased at the later levels and all eventually became significant.

Adolescent↗

PubMed2006

TNF and TNF receptor expression and insulin sensitivity in human omental and subcutaneous adipose tissue--influence of BMI and adipose distribution.

Tumour necrosis factor (TNF)alpha is implicated in the relationship between obesity and insulin resistance/ type 2 diabetes. In an effort to understand this association better we (i) profiled gene expression patterns of TNF, TNFR1 and TNFR2 and (ii) investigated the effects of TNF on glucose uptake in isolated adipocytes and adipose tissue explants from omental and subcutaneous depots from lean, overweight and obese individuals. TNF expression correlated with expression of TNFR2, but not TNFR1, and TNF and TNFR2 expression increased in obesity. TNFR1 expression was higher in omental than in subcutaneous adipocytes. Expression levels of TNF or either receptor did not differ between adipocytes from individuals with central and peripheral obesity. TNF only suppressed glucose uptake in insulin-stimulated subcutaneous tissue and this suppression was only observed in tissue from lean subjects. These data support a relationship between the TNF system and body mass index (BMI), but not fat distribution, and suggest depot specificity of the TNF effect on glucose uptake. Furthermore, adipose tissue from obese subjects already appears insulin 'resistant' and this may be a result of the increased TNF levels.

Abdominal Fat↗

PubMed2026

Disentangling adiposity-related and non-adiposity-related genetic pathways for type 2 diabetes.

OBJECTIVE: To identify circulating proteins associated with type 2 diabetes (T2D) risk through pathways not fully explained by body mass index (BMI), and to assess therapeutic actionability. RESEARCH DESIGN AND METHODS: We applied GWAS-by-subtraction within a genomic structural equation model to European ancestry summary statistics for T2D (74,124 cases, 824,006 controls) and BMI (n = 681,275), partitioning T2D liability into BMI-related and BMI-subtracted components. We then performed proteome-wide Mendelian randomization (MR) using cis-protein quantitative trait loci from four plasma proteomics cohorts: ARIC, deCODE, Fenland, and the UK Biobank Pharma Proteomics Project. Prioritized proteins passed sensitivity analyses with alternative MR methods and were supported by colocalization evidence. Tissue-resolution regulatory support was assessed using cis-eQTL colocalization across GTEx and pancreatic islet, subcutaneous adipose, and whole-blood resources. Actionability was evaluated using the druggable genome and Open Targets. RESULTS: GWAS-by-subtraction attenuated the genetic correlation between BMI and BMI-subtracted T2D from 0.54 (SE 0.02) to 0.35 (SE 0.02). Proteome-wide MR prioritized 29 proteins for BMI-subtracted T2D. Thirteen showed eQTL colocalization in at least one tissue, implicating liver and intermediary metabolism (GCDH, NOTCH2), pancreatic islet biology (CTRB2, MANBA), adipose and Wnt signaling (RSPO3, GALNT3), and whole blood regulatory signals (PAM, SNUPN). Sixteen proteins were classified within druggable-genome Tiers 1-3, and five had existing Open Targets compounds. CONCLUSIONS: Integrating GWAS-by-subtraction, proteome-wide MR, and colocalization nominated 29 proteins associated with T2D liability not fully explained by BMI. These findings highlight genetically supported targets for follow-up studies of T2D therapies that complement weight-centered approaches.

Journal Article↗

PubMed2004

[From cytogenetics to cytogenomics of adipose tissue tumors: 2. Malignant adipose tissue tumors].

Malignant adipose tissue tumors, also called liposarcomas, are the most common sarcoma of adult life. They may be hard to distinguish from benign adipose tissue tumors as well as from other types of sarcomas. Well-differentiated liposarcomas and myxoid liposarcomas are the two histological subtypes that have been best characterized at the genetic level. The defining genetic features of well-differentiated liposarcoma cells are supernumerary circular ("ring") and giant linear rod chromosomes. These rings and giant chromosomes contain amplification of the 12q14-15 region, including the MDM2 gene, associated with coamplification of various other chromosomal regions. In addition, they most often lack alpha-satellite centromeric sequences. The detection of MDM2 amplification is a valuable tool for the differential diagnosis between well-differentiated liposarcomas and lipomas. Dedifferentiated liposarcomas usually present with patterns of MDM2 amplification similar to those observed in well-differentiated liposarcomas. In addition, recent CGH-array studies suggest that co-amplification of MDM2 with the 6q23-25 region might be a specific feature. Myxoid and round-cell liposarcomas are characterized by a translocation t(12;16)(q13;p11) that fuses the DDIT3 and FUS genes. A rare variant translocation t(12;22) that fuses DDIT3 with EWS has also been described. The genetics of pleomorphic liposarcoma is still obscure. Pleomorphic liposarcomas show complex karyotypes with many numerical and structural chromosomal aberrations. To date, no specific molecular abnormality has been identified.

Chromosomes, Human, Pair 12↗

PubMed1987

[Effect of an adipose and an adipose-free body weight on central and regional hemodynamics in men of working age without arterial hypertension].

A combined anthropometric and clinico-instrumental investigation of 137 men aged 20 to 59 without arterial hypertension showed the effect of adipose and adipose-free tissue mass and the ratio of both components on the functional status of hemodynamics in increased adiposis and its preceding stages. With growing adiposis change in the values of two body mass components was accompanied by more significant shifts of actual and specific indices of central hemodynamics as compared to those of regional hemodynamics (in the leg).

Adult↗

PubMed1981

[Long-term effects of weight reduction on body weight and metabolic parameters in adipose non-diabetics and adipose maturity-onset diabetics].

In 28 adipose patients (15 females, 13 males) with normal carbohydrate tolerance and in 35 adipose maturity-onset-diabetics (27 females, 8 males) a significant reduction of the ideal weight index was achieved by a stationary zero diet. The serum fasting values of triglycerides. cholesterol and uric acid decreased. The clearest influence was found in pathologically increased values. This also concerns the improvement of the glucose tolerance in diabetics, which is expressed in the change of the antidiabetic regime. 48.5 +/- 11.7 months after the cure in the after-examined patients with normal carbohydrate tolerance (n = 27) a slight decrease of the weight, in the group of diabetics (n = 31) a slight increase was observed. Despite these slight, non-significant changes of weight the situation in the carbohydrate, fat and purin metabolism on an average deteriorated.

Adult↗

PubMed1995

Thyroid hormone and norepinephrine signaling in brown adipose tissue. II: Differential effects of thyroid hormone on beta 3-adrenergic receptors in brown and white adipose tissue.

UNLABELLED: beta 3-adrenergic receptors (AR) are predominantly expressed in brown (BAT) and white adipose tissue (WAT), being more abundant in the former. There is growing interest in these receptors because of their potential to be pharmacologically targeted to control energy expenditure and lipid accretion. We have examined, in BAT and WAT of rats, the effect of thyroid hormone on the expression of beta 3-AR and their contribution to cAMP generation. Receptor density was assessed with the nonselective beta 3-AR ligand [125I]-cyanopindolol ([125I]-CYP) and the highly selective beta 3-AR agonist CL3216,243. beta 3-AR messenger RNA (mRNA) was analyzed by Northern blotting of total BAT and WAT RNA. Generation of cAMP by brown adipocytes in response to norepinephrine (NE) and CL316,243 was measured by RIA. In BAT, beta 3-AR can account for as much as 50% of the maximal cAMP response to NE, whereas in WAT these receptors probably account for all the effect of NE. In hypothyroidism. BAT beta 3-AR number is increased, as are beta 3-AR mRNA (4- to 6-fold) and the relative contribution of these receptors to the maximal cAMP production. In contrast, both beta 3-AR number and mRNA levels are reduced in WAT of hypothyroid rats. The injection of T3 to hypothyroid rats reverts the changes in beta 3-AR within 24 h, and T3 excess causes a greater than 90% reduction in beta 3-AR mRNA in BAT but a 5-fold increase in WAT. In both tissues, hypothyroidism is associated with a marked reduction in the capacity to generate cAMP, but this is not completely restored even after 2 days of a receptor-saturating dose of T3. CONCLUSIONS: 1) thyroid hormone differentially affects the expression of beta 3-AR in BAT and WAT; 2) these effects of T3 are both rapid and marked and seem to take place at a pretranslational level; 3) in both tissues there is a postreceptor defect in the generation of cAMP that is corrected by T3 much later after the changes in beta 3-AR are reversed; and 4) thyroid hormone is among the known factors that most vigorously affect the expression of beta 3-AR.

Adipose Tissue↗

PubMed1984

Fatty acid synthesis in brown adipose tissue of the Mongolian gerbil (Meriones unguiculatus): influence of acclimation temperature on synthesis in brown adipose tissue and the liver in relation to whole-body synthesis.

Fatty acid synthesis was measured in vivo with 3H2O in Mongolian gerbils acclimated at different temperatures. At 31 degrees C the highest rate of synthesis was in the liver, and the liver accounted for approximately one half of whole-body synthesis. At 20 and 40 degrees C, the highest synthesis rate (per g tissue) occurred in brown adipose tissue, and this tissue was estimated to account for some 15% of whole-body synthesis at both these temperatures. In contrast to other rodent species whole-body fatty acid synthesis in the Mongolian gerbil was lower in cold-acclimated than warm-acclimated animals, despite the cold-induced increase in energy intake.

Acclimatization↗

PubMed1986

Partial protection against erucoyl-carnitine inhibition in hamster brown-adipose-tissue mitochondria is due to high CoA levels: a comparison with rat brown-adipose-tissue mitochondria.

Brown-adipose-tissue mitochondria isolated from golden hamsters were found to contain more CoA per mg protein than rat brown-fat mitochondria, and after incubation with erucoyl-carnitine, a higher free CoA level remained, than in rat mitochondria. In accordance with the suggestion (Alexson et al. (1985) Biochim. biophys. Acta 834, 149-158) that the inhibitory effect of erucoyl-carnitine on brown-fat mitochondrial respiration is entirely due to CoA sequestration, hamster mitochondria (with more CoA) were less sensitive to erucoyl inhibition than were rat mitochondria. Thus, increased mitochondrial CoA levels may augment the ability of animals to withstand the detrimental effects of a high erucoyl ester content of the diet.

Adipose Tissue, Brown↗

PubMed1997

Lipoprotein lipase controls fatty acid entry into adipose tissue, but fat mass is preserved by endogenous synthesis in mice deficient in adipose tissue lipoprotein lipase.

Lipoprotein lipase (LPL) is the rate-limiting enzyme for the import of triglyceride-derived fatty acids by muscle, for utilization, and adipose tissue (AT), for storage. Relative ratios of LPL expression in these two tissues have therefore been suggested to determine body mass composition as well as play a role in the initiation and/or development of obesity. To test this, LPL knockout mice were mated to transgenics expressing LPL under the control of a muscle-specific promoter (MCK) to generate induced mutants with either relative (L2-MCK) or absolute AT LPL deficiency (L0-MCK). L0-MCK mice had normal weight gain and body mass composition. However, AT chemical composition indicated that LPL deficiency was compensated for by large increases in endogenous AT fatty acid synthesis. Histological analysis confirmed that such up-regulation of de novo fatty acid synthesis in L0-MCK mice could produce normal amounts of AT as early as 20 h after birth. To assess the role of AT LPL during times of profound weight gain, L0-MCK and L2-MCK genotypes were compared on the obese ob/ob background. ob/ob mice rendered deficient in AT LPL (L0-MCK-ob/ob) also demonstrated increased endogenous fatty acid synthesis but had diminished weight and fat mass. These findings reveal marked alterations in AT metabolism that occur during LPL deficiency and provide strong evidence for a role of AT LPL in one type of genetic obesity.

Adipose Tissue↗

PubMed1979

The growth of adipose tissue in children and adolescents. Cross-sectional and longitudinal studies of adipose cell number and size.

Adipocyte size and number were determined in 288 subjects ranging in age from 4 mo to 19 yr. The study was performed in 110 obese and 178 non-obese subjects. 4-yr, longitudinal, follow-up studies were also performed in 132 subjects. The results demonstrate that the contribution of cell number and size to the growth of the fat depot in nonobese children varies with age. Deviations from this normal development were observed in obese children shortly after 1 yr of age. By 11 yr of age obese children exceeded the mean cell number found in nonobese adults. Indeed, obese subjects displayed more rapid and earlier elevations in both cell number and size, which were maintained throughout the study. Thus obese children display both quantitative and qualitative differences in fat tissue development when compared to nonobese children. The data indicate that the rate and type of adipose tissue cellular development one encounters in children may play a role in the development of the enlarged fat depots found in obese subjects.

Adipose Tissue↗

PubMed1996

Culture conditions supporting adipose conversion of stromal-vascular cells from bovine intramuscular adipose tissues.

The culture conditions which are able to support the differentiation of bovine intramuscular (i.m.) stromal-vascular (S-V) cells into adipocytes were investigated. Bovine i. m. S-V cells were able to undergo adipose conversion, assessed by emergence of lipid droplets and induction of glycerol-3-phosphate dehydrogenase (GPDH) activity, when treated with 0.25 microM dexamethasone and 0.5 mM 1-methyl-3-isobutylxanthine in a serum-deprived (0.1%) medium containing 850 nM insulin and 1 mM octanoate. Octanoate was essential for morphological differentiation and addition of 25 microM of cholesterol with octanoate induced higher GPDH activity. The differentiation of the cells was not observed in the medium containing 10% fetal calf serum which supported the cell proliferation of undifferentiated cells even after confluence. Similarly, both bovine brain extracts and muscle extracts inhibited the differentiation of S-V cells in the serum-deprived condition. These results suggest that the existence of lipids such as octanoate and the process of growth-arrest in preadipocytes and/or other cells are necessary for the differentiation of bovine S-V cells into adipocytes in culture.

1-Methyl-3-isobutylxanthine↗

PubMed1976

[Hormonal control of the adenyl cyclase activity of adipose cell membranes prepared from badger, rabbit, fox and rat adipose tissues].

1. We have shown differences in hormonal regulation of adenylate cyclase activity in fat cell ghosts prepared from rat, rabbit, fox and badger adipose tissue, under the influence of catecholamines, ACTH and insulin. a) In the rat, catecholamines induced a large stimulation (+315%) of adenylate cyclase. b) In the rabbit, ACTH was the most effective hormone. c) In the fox and the badger, only catecholamines could stimulate adenylate cyclase. d) In both rat and rabbit, insulin did not reduce spontaneous enzymatic activity. Moreover, the activation of adenylate cyclase by ACTH in the rabbit was not altered by insulin, while in the rat, this hormone slightly decreased epinephrine stimulation. 2. Hormonal regulation of adenylate cyclase correlated with the lipolytic response.

Adenylyl Cyclases↗

PubMed1989

Associations between plasma lipoprotein cholesterols, adiposity and adipose tissue distribution during adolescence.

Associations between changes with age in 'fat pattern' and lipoprotein cholesterols during adolescence were analyzed using serial data for 214 boys and girls between 11 and 18 years of age who were participants in the Fels Longitudinal Study. The logarithms of the ratios of the subscapular to lateral calf and the subscapular to triceps skinfold thicknesses increased with age in each sex, but the increases were greater in the boys. Plasma levels of HDL cholesterol decreased with age in the boys, but not in the girls. Within annual age-groups, neither plasma LDL cholesterol nor HDL cholesterol were correlated with percent body fat or either of the 'fat pattern' indices in each sex. In 51 children with serial data 5 years apart, changes with age in HDL cholesterol had significant negative correlations with changes in the 'fat pattern' indices that were independent of changes in percent body fat in the boys, but not in the girls. In the girls, changes in the indices were due to greater increases in the thickness of the subscapular skinfold than in the triceps and lateral calf skinfolds as percent body fat increased and were not associated with changes in levels of plasma lipoproteins. In the boys, changes in the 'fat pattern' indices were due to decreases in the thicknesses of the lateral calf and triceps skinfolds and increases in thickness of the subscapular skinfold as percent body fat decreased. These results suggest that a redistribution of adipose tissue occurs during adolescence in boys and is associated with decreases in HDL cholesterol.

Adipose Tissue↗