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Biomedical subjects

E Hell

Publications and source records attributed to E Hell.

At least 19 recordsLinked to original sources
PubMed2001

A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans.

Obesity is the most common nutritional disorder in Western society. Uncoupling protein-2 (UCP2) is a recently identified member of the mitochondrial transporter superfamily that is expressed in many tissues, including adipose tissue. Like its close relatives UCP1 and UCP3, UCP2 uncouples proton entry in the mitochondrial matrix from ATP synthesis and is therefore a candidate gene for obesity. We show here that a common G/A polymorphism in the UCP2 promoter region is associated with enhanced adipose tissue mRNA expression in vivo and results in increased transcription of a reporter gene in the human adipocyte cell line PAZ-6. In analyzing 340 obese and 256 never-obese middle-aged subjects, we found a modest but significant reduction in obesity prevalence associated with the less-common allele. We confirmed this association in a population-based sample of 791 middle-aged subjects from the same geographic area. Despite its modest effect, but because of its high frequency (approximately 63%), the more-common risk allele conferred a relatively large population-attributable risk accounting for 15% of the obesity in the population studied.

3' Untranslated Regions↗
PubMed2000

The Gln27Glu polymorphism in the beta2-adrenergic receptor gene is not associated with morbid obesity in Austrian women.

OBJECTIVE: Beta-adrenergic receptors (betaARs) play an important role in the regulation of energy expenditure and lipid mobilization. A Gl-27Glu polymorphism in the beta2-adrenergic receptor (beta2AR) gene has recently been associated with several indices of obesity in a female Caucasian population, while the same polymorphism exhibited no association with obesity in another, albeit male, population. METHODS: We have therefore studied possible associations of the Gln27Glu and the Gly16Arg polymorphisms in the beta2AR with BMI, plasma leptin and UCP-1 mRNA expression in the intraperitoneal adipose tissue in a population of Caucasian women. RESULTS: The frequencies of the Gln27 and the Gly16 alleles as well as the beta2AR haplotypes were similar in our morbidly obese and lean subjects. Furthermore, no association was found between the Gln27Glu or the Gly16Arg polymorphisms and plasma leptin or adipose tissue UCP-1 gene expression in either group. CONCLUSIONS: We conclude that the two polymorphisms in the beta2AR gene studied are not a major factor contributing to obesity in our population.

Adipose Tissue↗
PubMed2000

Leptin, peroxisome proliferator-activated receptor-gamma, and CCAAT/enhancer binding protein-alpha mRNA expression in adipose tissue of humans and their relation to cardiovascular risk factors.

Obesity is a prevalent disorder that increases the risk for premature cardiovascular disease. The adipose tissue itself plays an active role in the regulation of fuel metabolism and energy homeostasis by expressing a number of regulatory genes, such as leptin, peroxisome proliferator-activated receptor-gamma (PPARgamma), and CCAAT/enhancer binding protein-alpha (C/EBPalpha). To study the in vivo relationships among these genes and their associations with cardiovascular risk factors, plasma levels of leptin, lipids, apolipoproteins (apo), insulin, and glucose were measured in 216 obese, 165 nonobese, and 36 weight-losing postobese subjects. mRNA expression of leptin, PPARgamma, and C/EBPalpha in the extraperitoneal and intraperitoneal adipose tissue was quantified in subsets of subjects. In obese individuals, plasma leptin was associated with apoA-I (r=0.2346, P<0.001) and insulin (r=0.2125, P<0.002). Leptin and C/EBPalpha mRNA expression in extraperitoneal and intraperitoneal adipose tissue of obese patients was higher than in the respective tissues of nonobese or postobese subjects. No significant differences among the study groups were found for PPARgamma mRNA expression. Leptin, PPARgamma, and C/EBPalpha mRNA levels correlated with each other in the intraperitoneal and extraperitoneal fat of obese subjects, but multivariate analysis revealed that only C/EBPalpha was a predictor of leptin expression in extraperitoneal tissue (partial r=0.6096, P<0.001). Intraperitoneal PPARgamma expression was inversely related to fasting insulin (r=-0.2888, P<0.017) and a fasting insulin resistance index (r=-0.2814, P<0.021) in obese subjects. In postobese patients, intraperitoneal PPARgamma expression was associated with plasma HDL cholesterol (r=0.5695, P<0.018) and apoA-I (r=0.6216, P<0.008) but was inversely related to LDL cholesterol (r=-0.5101, P<0.03) and apoB (r=-0.6331, P<0.007). These findings suggest a relationship between plasma leptin and HDL metabolism as well as adipose-tissue site-dependent associations among leptin, C/EBP-alpha, and PPAR-gamma mRNA expression. Furthermore, our results suggest that C/EBP-alpha enhances leptin expression in vivo and that PPARgamma mRNA expression is inversely associated with cardiovascular risk factors.

Adipose Tissue↗
PubMed2000

Evaluation of health status and quality of life after bariatric surgery: comparison of standard Roux-en-Y gastric bypass, vertical banded gastroplasty and laparoscopic adjustable silicone gastric banding.

BACKGROUND: This study is a trial to compare the effects and outcomes of three different bariatric procedures performed in two centers. Standard Roux-en-Y gastric bypass was performed by Dr. Norman Samuels in Fort Lauderdale (Florida); vertical banded gastroplasty and laparoscopic adjustable silicone gastric banding were done in Hallein (Salzburg) by Dr. Emanuel Hell and Dr. Karl Miller. METHODS: In a prospective comparative study 30 matched patients from each group were followed to assess post-operative improvement in health status and quality of life, to compare the three different techniques. The Bariatric Analysis and Reporting Outcome System (BAROS) as described by Oria and Moorehead has been used for evaluation. RESULTS: The observation time was at least 3 years (3 to 8 years) in each individual case. A significant increase in quality of life and health status in 75% of the surgically-treated patients was observed when compared with a non-operated control group of morbidly obese patients. CONCLUSIONS: By utilizing BAROS it has been found possible to compare the results of different procedures done by different surgeons with different techniques, utilizing patients from different cultures and with different languages. The results of this comparative study favor the standard gastric bypass for the treatment of morbid obesity. This operation is superior to purely gastric restrictive procedures in weight loss and improvement of quality of life.

Adult↗
PubMed1999

Uncoupling protein-3 gene expression: reduced skeletal muscle mRNA in obese humans during pronounced weight loss.

AIMS: Uncoupling protein-3 is a member of a protein family that serves to dissipate energy in the form of heat thereby modulating energy expenditure. Alternative processing of uncoupling protein-3 transcripts results in two mRNA species that encode a large and small protein, perhaps differing in functional activity. Since obesity is associated with disrupted energy homeostasis, we measured muscle mRNA expression in morbidly obese and lean subjects. METHODS: The two uncoupling protein-3 mRNA species were quantified in muscle tissue using an RNase protection assay. Gene locus effects on mRNA expression were studied by quantitative allele-specific primer extension. RESULTS: In both obese and lean subjects, the mRNA species encoding the small protein isoform was twice as abundant as the mRNA species encoding the large protein isoform. Neither the total uncoupling protein-3 mRNA expression nor the molar abundance ratios of the two mRNA species differed between obese and lean male or female subjects. Women who had lost 37+/-22 kg of weight in response to dietary restriction and continued a hypocaloric diet displayed lower mRNA than obese (p<0.005) or lean women (p<0.05). Primer extension assays in lean and obese subjects showed similar allelic mRNA abundance in all but one subject studied. CONCLUSION: Muscle expression of the two uncoupling protein-3 mRNA species is similar in obese and lean people. In obese patients, prolonged hypocaloric diet downregulates uncoupling protein-3 mRNA expression in muscle and can thereby enhance its energy efficiency. Sequence substitutions at the gene locus may only be minor determinants of mRNA expression in muscle tissue.

Adult↗
PubMed1999

Laparoscopic adjustable gastric banding: a prospective 4-year follow-up study.

BACKGROUND: A body mass index of > or =40 kg/m2 represents clinically severe obesity and warrants operative treatment if requested. The adjustable silicone gastric band and the Swedish adjustable gastric band are recently produced laparoscopic gastric restrictive devices. The aim of this study was to assess all complications linked to both the available gastric bands in a long-term follow-up. METHODS: In a prospective study, the effects, complications, and outcomes of this procedure were analyzed. The complications found were divided into early and general complications, and complications correlated to the bands. The technique of laparoscopic adjustable gastric banding is described. Follow-up was performed by the operating team. RESULTS: Between July 1994 and August 1998, the authors operated on 158 patients and performed 102 adjustable silicone gastric bandings and 54 Swedish adjustable gastric bandings. The mean age at surgery was 36 years (range 17-72). The mean preoperative weight was 136 kg (89-230). Of 158 patients who underwent laparoscopic procedures, 156 (98%) could be followed up (mean 28 months; duration of follow-up, 6 weeks to 46 months). In early postoperative complications that required operation, one trocar wound hematoma (0.6%) and one wound infection of the port site (0.6%) were observed. The late complications that required reoperation were two pouch dilatations (1.3%), three band leakages (2%), one band migration (0.6%), and one late infection of the port (0.6%). A debanding operation was necessary in one patient because of esophageal dysmotility disorder. No early or late postoperative mortality was registered. The overall reoperation rate is currently about 7%. CONCLUSION: The operation is safe and effective. Moreover, adjustable gastric banding is fully reversible and is adjustable to the patient's needs. This study verifies the importance of correct operating technique. The authors' study and experience clearly indicate that laparoscopic adjustable gastric banding is an attractive alternative in the surgical treatment of morbid obesity.

Adolescent↗
PubMed1999

Allele-specific differences in apolipoprotein C-III mRNA expression in human liver.

BACKGROUND: Sequence variations at the apolipoprotein (apo)C-III gene locus have been associated with increased plasma triglycerides. In particular, the S2 allele of an SstI polymorphism in the 3' untranslated region has been associated with hypertriglyceridemia in many populations. The aim of this study was to determine whether the variant S2 allele is related to increased mRNA expression in vivo. METHODS: We measured allele-specific apoC-III expression in liver biopsies of five obese subjects, using restriction isotyping and a primer extension method, both based on the SstI polymorphism. RESULTS: The expression of mRNA by the S1 and S2 alleles was similar in two patients, whereas the mRNA encoded by the S2 allele was 14%, 26%, and 29% more abundant than the wild-type mRNA in the remaining three patients. Because other polymorphisms at the apoC-III gene locus have been implicated in the S2-associated hypertriglyceridemia, we determined apoC-III haplotypes comprising promoter polymorphisms at -935, -641, -630, -625, -482, -455, as well as the SstI sites and a BbvI site, both located in the 3' untranslated region. None of these polymorphisms nor any haplotype exhibited a perfect association with allele-specific expression, but variation at the T-482C site correlated in four of five subjects with the relative allele abundance. CONCLUSION: These data provide preliminary evidence for allele-specific differences in apoC-III mRNA expression in vivo and suggest that such differences may contribute to associations of apoC-III gene polymorphisms with hypertriglyceridemia.

3' Untranslated Regions↗
PubMed1998

Uncoupling protein-2 gene: reduced mRNA expression in intraperitoneal adipose tissue of obese humans.

The mitochondrial uncoupling protein-2 (UCP-2) is a recently discovered homologue of the brown adipose tissue-specific uncoupling protein and could be involved in the regulation of energy balance. Since obesity is associated with disturbed energy homeostasis, we tested the hypothesis that UCP-2 gene expression is deficient in this disorder. We determined, by a competitive reverse transcription-polymerase chain reaction assay, UCP-2 mRNA expression in intra- and extraperitoneal adipose tissues of 107 morbidly obese subjects and 31 lean control subjects. In both obese and non-obese subjects, UCP-2 mRNA abundance was higher in the intraperitoneal than in the extraperitoneal tissue (p < 0.05), but no association was observed between intra- and extraperitoneal expression in either group. Compared with lean control subjects, both male and female obese subjects displayed significantly lower average UCP-2 mRNA expression in the intraperitoneal adipose tissue (p < 0.006), while UCP-2 mRNA abundance in extraperitoneal adipose tissue was not different between obese and non-obese men and women. Intraperitoneal UCP-2 mRNA remained low in nine obese subjects who lost 23 +/- 12 kg of weight over a period of 10 +/- 5 months subsequent to weight reducing surgery. These data support the concept that impaired adipose tissue expression of UCP2 may play a role in the pathophysiology of obesity.

Adipose Tissue↗
PubMed1998

Plasma leptin levels: interaction of obesity with a common variant of insulin receptor substrate-1.

Obesity is associated with insulin resistance and other major cardiovascular risk factors. A common amino acid polymorphism at codon 972 of the insulin receptor substrate-1 (IRS-1) has been shown to interact with obesity in the expression of insulin resistance. The plasma concentration of the adipocyte-specific hormone leptin is increased in obesity and is correlated with adipose tissue mass. Because in vitro studies demonstrated inhibitory effects of leptin on insulin signaling, leptin may be involved in obesity-associated insulin resistance. To gain insight into the relationship between insulin and leptin in obesity, we studied plasma leptin levels and several cardiovascular risk factors, as well as their modification by the IRS-1 codon 972 genotype, in 156 obese individuals and 131 lean control subjects. In both groups, 10% of the subjects were heterozygous for the IRS-1 codon 972 variant. Obese individuals harboring the IRS-1 variant displayed significantly lower plasma concentrations of leptin than obese subjects without the polymorphism (means, 26.7 versus 37.8 ng/mL, P<0.0293). In a subgroup of obese patients, leptin mRNA abundance was measured in the adipose tissue and was significantly lower in carriers of the IRS-1 variant than in subjects with the wild-type variant (P<0.0291). Our data suggest that insulin signaling influences plasma leptin concentrations at the mRNA expression level and argue against leptin as a major causative factor of insulin resistance.

Adult↗
PubMed1998

Uncoupling protein-1 mRNA expression in obese human subjects: the role of sequence variations at the uncoupling protein-1 gene locus.

Uncoupling protein-1 (UCP-1) activity in brown adipose tissue increases thermogenesis, contributes to facultative energy expenditure in humans, and has been implicated in the pathogenesis of rodent obesity. To determine genetic factors controlling UCP-1 expression in humans, we measured intra- and extraperitoneal UCP-1 mRNA abundance levels by a competitive RT-PCR method and compared expression levels with common sequence variations in the beta3-adrenergic receptor gene and the distal UCP-1 gene promoter in obese human subjects. While median and average UCP-1 mRNA levels in both the intra- and extraperitoneal tissue were lower in subjects heterozygous for the Trp64Arg mutation in the beta3-adrenergic receptor gene, this difference was not statistically significant. However, a strong association of intraperitoneal UCP-1 mRNA abundance with the UCP-1 gene polymorphism at -3826 relative to the transcription start site was observed that explained 19.3% of the interindividual variability. The minor allele imparted a dose-dependent reduction on UCP gene expression. The importance of sequence variations at the UCP-1 gene locus as a common source of UCP-1 mRNA abundance variability was supported by allele-specific expression studies utilizing a newly identified polymorphism in exon 2 of the UCP-1 gene that predicts a substitution of alanine by threonine. In four subjects heterozygous for the -3826 polymorphism, the mRNA species transcribed from the wild-type allele accounted for 63+/-6% percent of total intraperitoneal mRNA abundance. In one subject homozygous for the minor promoter allele, wild-type mRNA was also more abundant than variant mRNA. Thus, the UCP-1 polymorphism at -3826 is probably only a marker for a frequent mutation causing reduced mRNA expression.

Adipose Tissue↗
PubMed1997

Human obese gene expression: alternative splicing of mRNA and relation to adipose tissue localization.

BACKGROUND: The adipocyte-specific protein leptin signals the size of the adipose tissue mass to hypothalamic regions, thereby influencing food intake and energy metabolism. Human obesity is often associated with high leptin levels implying leptin resistance or defective leptin function. Two leptin mRNA species differing only by the presence or absence of a CAG codon encoding glutamine at position 49 of the mature protein arise from alternative splicing owing to two splice acceptor sites immediately following each other at the intron 2 - exon 3 junction. Since glutamine 49 is part of a highly conserved region, we studied possible functional implications of alternative splicing for human obesity. METHODS: We determined, in lean and obese individuals, the relative abundance of both mRNA species in intra- and extraperitoneal adipose tissue in relation to ob gene transcript abundance and plasma leptin levels. RESULTS: Leptin mRNA levels in adipose tissue and concentrations of leptin in plasma were significantly higher in obese subjects than in controls. In both obese and control subjects, leptin mRNA levels were higher in extraperitoneal than in intraperitoneal adipose tissue. Furthermore, leptin mRNA abundance correlated with average fat cell size. In all tissue samples, the predominant ob gene transcript contained the codon for glutamine 49 and the molar ratio of the two leptin mRNA species was similar in patients and controls. No correlation was observed between splice site usage and leptin mRNA abundance or leptin concentration in plasma in our study group. CONCLUSIONS: Differences in the primary structure of leptin due to the presence or absence of glutamine 49 are unlikely to contribute to the apparent 'leptin resistance' commonly observed in obese individuals.

Adipocytes↗
PubMed1997

Uncoupling protein gene: quantification of expression levels in adipose tissues of obese and non-obese humans.

The mitochondrial uncoupling protein (UCP), which is exclusively expressed in brown adipose tissue, regulates energy expenditure in rodents but its importance in the energy homeostasis of adult humans is uncertain. To study associations of UCP gene expression with human obesity, we determined, by a competitive reverse transcription-polymerase chain reaction assay, UCP mRNA expression levels in intra- and extraperitoneal adipose tissues of 79 obese subjects and 17 lean controls. UCP mRNA and internal standard RNA were reverse transcribed and coamplified in one reaction in which the same primers were used. The signal intensities of UCP mRNA products were compared with the signal intensities of standard RNA products to quantify UCP mRNA abundance. UCP mRNA was detected in all intra- and extraperitoneal adipose tissues studied. In both obese and non-obese subjects, UCP mRNA abundance was higher in the intraperitoneal than in the extraperitoneal tissue (P < 0.001). Compared to lean controls, morbidly obese subjects showed a significantly lower age- and gender-adjusted UCP mRNA expression level in the intraperitoneal adipose tissue (3.467 +/- 2.483 vs. 6.917 +/- 4.292 amol/fmol beta-actin mRNA; mean +/- SD, P < 0.002), while UCP mRNA abundance in extraperitoneal adipose tissue did not differ between obese and nonobese subjects. These data are consistent with reduced energy expenditure in obesity, but it remains to be determined whether the association of decreased intraperitoneal UCP mRNA expression with obesity status reflects a causal contribution of brown adipose tissue function to the pathogenesis of obesity.

Adipose Tissue, Brown↗
PubMed1996

Adjustments and Leak Detection of the Adjustable Silicone Gastric Band (ASGB) and Lap-Bandtrade mark Adjustable Gastric Band (LAGB) System.

BACKGROUND: The detection of a leakage in the system of the adjustable silicone gastric band (ASGB) may be difficult. Gastrografin injection into the port should be avoided because it acts like a glue and blocks the system. METHODS: A syringe containing saline and a syringe containing Thallium-201 chloride is connected to the 4-way stopcock which is connected to the needle. The needle is pushed into the port. The position is confirmed by injection and aspiration of saline. 2 ml of TL-201 chloride (74 MBp) is injected to locate the leakage in the system with planar images with a gamma camera (Elscint SP 6), 30 min, 2, 3, and 24 h after injection. RESULTS: The original ASGB was provided with an injection reservoir which, in our series, was found to be leaking in four cases (3%). CONCLUSIONS: Our technique for adjustment and leak detection appears to be simple and effective. Band-related problems such as reservoir leak should disappear with improvement of the material.

Journal Article↗
PubMed1996

[10 years experience with vertical banded gastroplasty for operative therapy of morbid obesity].

Since 1985 vertical banded gastroplasty has been performed in a consecutive series of 300 morbid obese patients. Two years after operation the average weight loss was 46 kg or 67% of the initial overweight. There was one postoperative and one late death. The reintervention rate was 2% per year for the first 5 years. In the treatment of morbid obesity vertical banded gastroplasty is an effective procedure, rapid and simple to perform and without irreversible changes of the digestive tract.

Adolescent↗
PubMed1995

Local vs Systemic Antibiotics to Decrease Wound Complications following Vertical Banded Gastroplasty: Results of a Prospective Randomized Trial.

BACKGROUND: Obesity is generally regarded as one factor predisposing to wound infection. Most reports of infection rates range from I to 16% for similar procedures. In our department the wound infection rate for morbidly obese patients was 12% without perioperative antibiotics. METHODS: In a prospective randomized study we compared local gentamicin-collagen fleece application in the subcutaneous layer with patients receiving a perioperative single I.V. dose of amoxicillin-clavulanic acid 2.2 g. We examined the results of different perioperative management of antibiotics on 50 morbidly obese patients who underwent vertical banded gastroplasty from March 1993 to August 1994. The fascial, subcutaneous and skin closure technique were identical in the two groups. For both groups we used a closed-suction system to drain the bottom of the deep subcutaneous layer. On the third postoperative day, the subcutaneous drains were removed. Patients stayed in hospital an average of 10 days. They had follow-up visits after 1, 3 and 6 months, and then yearly. RESULTS: None of the 50 patients developed a wound infection, hematoma, or seroma in the hospital. During the follow-up (median 6 months), no patient developed a wound abscess. CONCLUSIONS: We believe that perioperative antibiotic management is an important factor in obtaining a low infection rate.

Journal Article↗
PubMed1992

[Effects of surgical therapy of extreme obesity on physical and psychological outcome].

More than 400 patients with morbid obesity were treated surgically in our unit over the past 18 years. Three different methods (intestinal bypass, bilio-intestinal shunt and vertical banded gastroplasty) were used. In order to assess any postoperative increase in life quality and to compare the three different techniques, 25 matched patients from each group were followed up and the findings compared with a group of non-operated morbidly obese persons. Psychological tests were also supplied. Irrespective of the technique performed a significant increase in quality of life was obtained in 75% of the cases.

Activities of Daily Living↗