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- Baghaei, Fariba, 1964, et al.
(författare)
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The CYP19 gene and associations with androgens and abdominal obesity in premenopausal women.
- 2003
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Ingår i: Obesity research. - : Wiley. - 1071-7323. ; 11:4, s. 578-85
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Elevated androgens in women are associated with type 2 diabetes and are dependent on the conversion to estrogens by aromatase cytochrome P450. Polymorphisms of a tetranucleotide repeat [TTTA](n) in the fourth intron of the CYP19 gene are associated with endocrine-dependent diseases and were examined in relation to hormone levels and disease risk factors in premenopausal women. RESEARCH METHODS AND PROCEDURES: A population sample of women born in 1956 (n = 270) were genotyped for this polymorphism and the results set in relation to steroid hormones, including saliva cortisol, anthropometric variables, estimates of insulin, glucose and lipid metabolism, and blood pressure. RESULTS: Seven tetranucleotide repeat [TTTA](n) alleles were detected with allelic sizes of 168 to 195 bp, with a TCT deletion/insertion (168/171 bp) upstream of this microsatellite. Smoking was associated with elevated androgens (p = 0.005 to 0.019). Using the median (average stretch, 177.5 bp) as a dividing line, nonsmoking women with the shorter microsatellite had higher free testosterone (p = 0.018) and lower sex hormone binding globulin (p = 0.033). These differences were pronounced with the 168-bp allele. Such women were also characterized by a less-substantial decrease of morning cortisols ("unwinding"; p = 0.035) and central obesity (abdominal sagittal diameter, p = 0.049) and had waist/hip circumference ratios of borderline significance (p = 0.064). DISCUSSION: The results indicate that, in premenopausal women, a short microsatellite in the fourth intron of the CYP19 gene, caused by a TCT deletion upstream the [TTTA](n) tract, is associated with elevated androgens, perturbed regulation of the hypothalamic-pituitary-adrenal axis, and abdominal obesity.
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- Baghaei, Fariba, 1964, et al.
(författare)
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The lean woman.
- 2002
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Ingår i: Obesity research. - : Wiley. - 1071-7323. ; 10:2, s. 115-21
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In the current obesity epidemic, the ability to remain lean is beginning to be uncommon. Therefore, it was considered of interest to characterize such subjects. RESEARCH METHODS AND PROCEDURES: From a population of premenopausal women (n = 270), all 40 years of age, those with a similar body mass index (BMI) as women at the age of 21 years, born the same year (BMI = 21.1 kg/m(2)) were selected among nonsmokers and compared with the remaining nonsmoking women. RESULTS: Lean women showed, as expected, low waist-to-hip circumference ratio and abdominal sagittal diameter as well as absence of other disease risk factors. Compared with the remaining women, 17 beta-estradiol was high and androgens were low, whereas insulin-like growth factor I and thyroid hormones showed no differences. Dihydroepiandrosterone sulfate was lower, whereas cortisol, measured in saliva repeatedly over a day, and adrenocorticotropin hormone were not different. Results from questionnaires indicated higher education and socioeconomic status, frequent sports activities, and better psychosocial adaptation and psychological health. A tetranucleotide repeat polymorphism in the fourth [corrected] intron of the aromatase P450 gene was longer among the lean (187 base pairs) than the rest of the women. Women with opposite phylogenetic characteristic have a short microsatellite (168 base pairs) in this gene locus. DISCUSSION: Lean, nonsmoking women enjoy an excellent health in not only anthropometric and metabolic factors, but also in neuroendocrine, endocrine, and psychological variables. The endocrine measurements suggest a well-functioning aromatase, which in turn might have a genetic background, contributing to health. The aromatase gene might be important for regulation of body fat mass.
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- Ben-Menachem, Elinor, 1945, et al.
(författare)
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Predictors of weight loss in adults with topiramate-treated epilepsy.
- 2003
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Ingår i: Obesity research. - 1071-7323. ; 11:4, s. 556-62
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We examined predictors of weight loss with topiramate, an anticonvulsant associated with weight loss in adults. RESEARCH METHODS AND PROCEDURES: In this uncontrolled, prospective clinical trial, topiramate was added to existing anticonvulsants in adults (40 to 110 kg) with partial-onset seizures. Primary measurements were change from baseline weight after 3 months and 1 year in patients completing 1 year of topiramate treatment (N = 38). Physiological and metabolic measures were analyzed for correlation with weight loss during topiramate treatment. RESULTS: In patients who completed 1 year of topiramate treatment, baseline weight was reduced in 82% at 3 months and in 86% at 1 year. Mean body weight was reduced 3.0 kg (3.9% of baseline) at 3 months and 5.9 kg (7.3%) at 1 year. In obese patients [body mass index (BMI) >/= 30 kg/m(2)], mean weight loss was 4.2 kg (4.3%) at 3 months and 10.9 kg (11.0%) at 1 year. Weight loss was primarily caused by reduction in body fat mass. For all patients, weight loss at 3 months correlated most strongly with reduced caloric intake (p = 0.02). At 1 year, caloric intake had returned to baseline levels; weight loss correlated most strongly with higher baseline BMI (p = 0.0007). DISCUSSION: Our results suggest that weight loss occurs in most adults treated with topiramate and is sustained for at least 1 year. Reduced caloric intake may account, in part, for weight loss during early treatment. The pattern of weight loss differs according to baseline BMI, with obese patients experiencing greater weight loss during continued therapy.
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- Björnheden, Tom, 1945, et al.
(författare)
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Computerized determination of adipocyte size.
- 2004
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Ingår i: Obesity research. - 1071-7323. ; 12:1, s. 95-105
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Fat cell size is a fundamental parameter in the study of adipose tissue metabolism, because it markedly influences the cellular rates of metabolism. Previous techniques for the sizing of adipocytes are often complicated or time-consuming. The aim of this study was to develop a new, computerized method for rapid and accurate determination of adipocyte size in a cell suspension obtained by incubating human or rat adipose tissue biopsies with collagenase. RESEARCH METHODS AND PROCEDURES: The cell suspension was placed between a siliconized glass slide and a cover slip. Using the reference method [designated as (R)], the cell diameters were determined manually using a microscope with a calibrated ocular. The new method presented here [designated as (C)] was based on computerized image analysis. RESULTS: After two well-defined corrective adjustments, measurements with (R) and (C) agreed very well. The small remaining differences seemed, in fact, to depend on inconsistencies in (R). DISCUSSION: We propose that (C) constitutes a valuable tool to study fat cell size, because this method is fast and allows the assessment of a sufficient number of cells to get reliable data on size distribution. Furthermore, images of cell preparations may be stored for future reference.
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- Carlsson, Björn, 1958, et al.
(författare)
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Obese (ob) gene defects are rare in human obesity
- 1997
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Ingår i: Obesity Research. - 1071-7323 .- 1550-8528. ; 5:1, s. 30-5
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Tidskriftsartikel (refereegranskat)abstract
- Our knowledge of the role of the recently cloned ob-protein (leptin) in the regulation of body fat stores is largely derived from experiments performed in mice. Different mouse models exhibit abnormalities in ob-gene expression, with extreme overexpression in mice which lack bioactive ob-protein, have nonfunctional ob-receptors or hypothalamic lesions, and undetectable expression in mice with suggested defects in regulatory elements. The aim of this study is to examine if defects, corresponding to those in mice, exist in human obesity. Adipose tissue was obtained from 94 adult obese subjects and from six children who had developed obesity after surgery in the hypothalamic region. Total RNA was isolated and ob-gene expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot. The coding region of the ob-gene was sequenced in both directions in the 94 obese adults. No mutations were detected in the coding region of the ob-gene and ob-gene expression was detectable in all subjects and none of the subjects had an extreme overexpression. There was no systematic increase in ob-expression in obese children with hypothalamic disease compared to their healthy brothers and sisters. These results show that severe abnormalities involving the ob-gene, analogous to those described in mouse models, are rare in human obesity. We therefore conclude that the cloning and subsequent analysis of the ob-gene has not provided information that can, by itself, explain the genetic component in the development of human obesity.
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- Cedergren, Marie, 1963-, et al.
(författare)
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Maternal obesity and infant heart defects
- 2003
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Ingår i: Obesity Research. - 1071-7323 .- 1550-8528. ; 11:9, s. 1065-1071
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study determined whether obese women have an increased risk of cardiovascular defects in their offspring compared with average weight women. Research Methods and Procedures: In a case-control study, prospectively collected information was obtained from Swedish medical health registers. The study included 6801 women who had infants with a cardiovascular defect and, as controls, all delivered women (N = 812,457) during the study period (1992 to 2001). Infants with chromosomal anomalies or whose mothers had pre-existing diabetes were excluded. Obesity was defined as BMI >29 kg/m2, and morbid obesity was defined as BMI >35 kg/m2. Comparisons were made with average weight women (BMI = 19.8 to 26 kg/m2). Results: In the group of obese mothers, there was an increased risk for cardiovascular defects compared with the average weight mothers [adjusted odds ratio (OR) = 1.18, 95% CI, 1.09 to 1.27], which was slightly more pronounced for the severe types of cardiovascular defects (adjusted OR = 1.23, 95% CI, 1.05 to 1.44). With morbid obesity, the OR for cardiovascular defects was 1.40 (95% CI, 1.22 to 1.64), and for severe cardiovascular defects, the OR was 1.69 (95% CI, 1.27 to 2.26). There was an increased risk for all specific defects studied among the obese women, but only ventricular septal defects and atrial septal defects reached statistical significance. Discussion: In this sample, a positive association was found between maternal obesity in early pregnancy and congenital heart defects in the offspring. A suggested explanation is undetected type 2 diabetes in early pregnancy, but other explanations may exist.
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- Cornier, Marc-Andre, et al.
(författare)
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Insulin sensitivity determines the effectiveness of dietary macronutrient composition on weight loss in obese women.
- 2005
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Ingår i: Obesity research. - 1071-7323. ; 13:4, s. 703-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether macronutrient composition of a hypocaloric diet can enhance its effectiveness and whether insulin sensitivity (Si) affects the response to hypocaloric diets. RESEARCH METHODS AND PROCEDURES: Obese nondiabetic insulin-sensitive (fasting insulin < 10 microU/mL; n = 12) and obese nondiabetic insulin-resistant (fasting insulin > 15 microU/mL; n = 9) women (23 to 53 years old) were randomized to either a high carbohydrate (CHO) (HC)/low fat (LF) (60% CHO, 20% fat) or low CHO (LC)/high fat (HF) (40% CHO, 40% fat) hypocaloric diet. Primary outcome measures after a 16-week dietary intervention were: changes in body weight (BW), Si, resting metabolic rate, and fasting lipids. RESULTS: Insulin-sensitive women on the HC/LF diet lost 13.5 +/- 1.2% (p < 0.001) of their initial BW, whereas those on the LC/HF diet lost 6.8 +/- 1.2% (p < 0.001; p < 0.002 between the groups). In contrast, among the insulin-resistant women, those on the LC/HF diet lost 13.4 +/- 1.3% (p < 0.001) of their initial BW as compared with 8.5 +/- 1.4% (p < 0.001) lost by those on the HC/LF diet (p < 0.04 between two groups). These differences could not be explained by changes in resting metabolic rate, activity, or intake. Overall, changes in Si were associated with the degree of weight loss (r = -0.57, p < 0.05). DISCUSSION: The state of Si determines the effectiveness of macronutrient composition of hypocaloric diets in obese women. For maximal benefit, the macronutrient composition of a hypocaloric diet may need to be adjusted to correspond to the state of Si.
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- Gabrielsson, Britt, 1957, et al.
(författare)
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Depot-specific expression of fibroblast growth factors in human adipose tissue.
- 2002
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Ingår i: Obesity research. - : Wiley. - 1071-7323 .- 1550-8528. ; 10:7, s. 608-16
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the expression of several fibroblast growth factors (FGFs) and FGF-receptors (FGFRs) in human adipose tissue and adipose-tissue cell fractions obtained from both subcutaneous (sc) and omental (om) depots.
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- Gabrielsson, Britt, 1957, et al.
(författare)
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Evaluation of reference genes for studies of gene expression in human adipose tissue.
- 2005
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Ingår i: Obesity research. - 1071-7323 .- 1550-8528. ; 13:4, s. 649-52
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to evaluate reference genes for expression studies of human adipose tissue. RESEARCH METHODS AND PROCEDURES: Using 52 human adipose tissue expression profiles (HU95), 10 putative reference genes with the lowest variation in expression levels were selected for further studies. Expression stability of these 10 novel and 5 previously established reference genes was evaluated by real-time reverse transcriptase-polymerase chain reaction analysis. For this purpose, 44 adipose tissue biopsies from 27 subjects were chosen to include a wide range of parameters such as sex, age, BMI, depot origin, biopsy procedure, and effects of nutrition. RESULTS: LRP10 was identified as the gene with the least variation in expression levels. The frequently used reference genes RPLP0, 18S rRNA, PPIA, ACTB, and GAPD were ranked as 4, 6, 7, 8, and 10, respectively. DISCUSSION: Our results suggest that LRP10 is a better choice as reference for expression studies of human adipose tissue compared with the most frequently used reference genes.
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- Gabrielsson, Britt, 1957, et al.
(författare)
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High expression of complement components in omental adipose tissue in obese men.
- 2003
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Ingår i: Obesity research. - : Wiley. - 1071-7323 .- 1550-8528. ; 11:6, s. 699-708
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Accumulation of visceral fat is recognized as a predictor of obesity-related metabolic disturbances. Factors that are predominantly expressed in this depot could mediate the link between visceral obesity and associated diseases. RESEARCH METHODS AND PROCEDURES: Paired subcutaneous and omental adipose tissue biopsies were obtained from 10 obese men. Gene expression was analyzed by DNA microarrays in triplicate and by real-time polymerase chain reaction. Serum C3 and C4 were analyzed by radial immunodiffusion assays in 91 subjects representing a cross section of the general population. Body composition was measured by computerized tomography. RESULTS: Complement components C2, C3, C4, C7, and Factor B had higher expression in omental compared with subcutaneous adipose tissue ( approximately 2-, 4-, 17-, 10-, and 7-fold, respectively). In addition, adipsin, which belongs to the alternative pathway, and the classical pathway components C1QB, C1R, and C1S were expressed in both depots. Analysis of tissue distribution showed high expression of C2, C3, and C4 in omental adipose tissue, and only liver had higher expression of these genes. Serum C3 levels correlated with both visceral and subcutaneous adipose tissue in both men (r = 0.65 and p < 0.001 and r = 0.52 and p < 0.001, respectively) and women (r = 0.34 and p = 0.023 and r = 0.49 and p < 0.001, respectively), whereas C4 levels correlated with only visceral fat in men (r = 0.36, p = 0.015) and with both depots in women (visceral: r = 0.58, p < 0.001; and subcutaneous: r = 0.51, p < 0.001). DISCUSSION: Recent studies show that the metabolic syndrome is associated with chronically elevated levels of several immune markers, some of which may have metabolic effects. The high expression of complement genes in intra-abdominal adipose tissue might suggest that the complement system is involved in the development of visceral adiposity and/or contributes to the metabolic complications associated with increased visceral fat mass.
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- Gabrielsson, Britt, 1957, et al.
(författare)
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Partial genome scale analysis of gene expression in human adipose tissue using DNA array
- 2000
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Ingår i: Obesity Research. - 1071-7323 .- 1550-8528. ; 8:5, s. 374-84
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Large scale analysis of gene expression in adipose tissue provides a basis for the identification of novel candidate genes involved in the pathophysiology of obesity. Our goal was to explore gene expression in human adipose tissue at a partial genome scale using DNA array. RESEARCH METHODS AND PROCEDURES: Labeled cDNA, derived from human adipose tissue poly(A+) RNA, was hybridized to a DNA array containing over 18,000 human expressed sequence-tagged (EST) clones. The results were analyzed by database searches. RESULTS: Homology searches of the 300 EST clones with highest hybridization signals revealed that 145 contained DNA sequences identical to known genes and 79 could be linked to UniGene clusters. Of the 145 identified genes, 136 were nonredundant and subsequently characterized with respect to function and chromosomal localization by searching MEDLINE, UniGene, GeneMap, OMIM, SWISS-PROT, the Genome Database, and the Location Data Base. The identified genes were grouped according to their putative functions; cell/organism defense (9.6%), cell division (5.1%), cell signaling/communication (19.8%), cell structure/motility (12.5%), gene/ protein expression (16.9%), metabolism (16.2%), and unclassified (19.8%). Less than 50% of these genes have previously been reported to be expressed in adipose tissue. The chromosomal localization of 268 genes strongly expressed in adipose tissue showed that their relative abundance was significantly increased on chromosomes 11, 19, and 22 compared to the expected distribution of the same number of random genes. DISCUSSION: Our study resulted in the identification of numerous genes previously not reported to be expressed in adipose tissue. These results suggest that DNA array is a powerful tool in the search for novel regulatory pathways within adipose tissue on a scale that is not possible using conventional methods.
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