[Role of infection in the pathogenesis of obesity]. / Úloha infekce v patogenezi obezity.

Current global epidemic of obesity is mainly related to increased consumption of high energy density foods and sedentary lifestyle that leads to a positive energy balance with subsequent accumulation of fat stores, primarily in genetically predisposed individuals. However, additional pathogenetic factors should be considered, including an infection. Several viruses causing obesity have been described in mice, chicken, rats, hamsters and monkeys. In humans, a significant positive association between being overweight and IgG antibodies was found for Helicobacter pylori and Chlamydia pneumoniae. This association of bacterial infections with increased BMI might not represent a causal relationship but could be a marker for greater susceptibility of obese individuals to infection. Crucial role in the development of "infectious obesity" in humans may be played by adenovirus infection, particularly AD-36 type that is also capable of inducing obesity in experimental animals as chicken, mice and monkeys. AD-36-induced obesity is paradoxically associated with lower levels of serum cholesterol and triglycerides both in humans and in experimental animals. Moreover, AD-36 enhances insulin sensitivity and improves hepatic steatosis. AD-36 effects in target organs as adipose tissue, liver and skeletal muscle are mediated through the viral protein E4orf1. This way AD-36 improves metabolic profile, as indicated by a greater glucose uptake by adipose tissue and skeletal muscle, reduced glucose output by hepatocytes, increased adiponectin levels and increased expression of adipogenic genes as peroxisome proliferator-activated receptor gamma. If E4orf1 improves glycemic control without reducing dietary fat intake and body fat stores, this viral protein would be highly valuable to develop novel anti-diabetic agents that mimic its effects.Key words: obesity, infection, adenovirus AD-36, diabetes mellitus, lipid profile, insulin sensitivity.

Do we need anti-obesity drugs?

The increasing global prevalence of obesity urgently requires an implementation of efficient preventive and therapeutic measures. Weight loss and its maintenance should be considered one of the most important strategies to reduce the incidence of obesity-related co-morbidities such as diabetes and cardiovascular diseases. Lifestyle modification focused on diet and physical activity represents the essential component of any kind of weight management. However, only an intensive lifestyle intervention can be efficient in terms of long-term weight loss. Anti-obesity drugs affect different targets in the central nervous system or peripheral tissues and improve regulatory and metabolic disturbances that contribute to the development of obesity. Anti-obesity medications provide modest additional fat loss to that achieved by lifestyle modification alone, reduce visceral fat stores, improve programme adherence, weight loss maintenance, diminish obesity-related health risks and improve a quality of life. Anti-obesity drugs do play a role in weight management. Their replacement with placebo is followed by weight regain. Due to adverse events, several anti-obesity drugs were withdrawn from the market over the past few years and currently only orlistat remains available for long-term obesity management. Drug withdrawals, failure of clinical trials with several new anti-obesity compounds as well as inappropriate demands of drug regulating agencies concerning the study protocol led to scepticism about the perspectives in the pharmacotherapy of obesity. However, recently developed anti-obesity medications such as gut hormone analogues and drug combinations provided encouraging results in terms of weight loss, safety and improvement of cardio-metabolic health risks.

Hypogonadotropic hypogonadism in a homozygous MC4R mutation carrier and the effect of sibutramine treatment on body weight and obesity-related health risks.

OBJECTIVE: The first aim of our study was to define the hypogonadism manifested by low testosterone levels and incomplete male secondary sex characteristics in a 20-year-old male homozygous MC4R mutation carrier (G181D). The second aim of our study was to evaluate the effect of the anti-obesity drug sibutramine in this patient who failed to respond to an intensive lifestyle intervention and exhibited continuous weight gain. CASE REPORT: Anthropometric, biochemical, hormonal and psycho-behavioural parameters were investigated both at baseline and after a 1-year sibutramine treatment. To characterise the hypogonadism, sex steroid profile, concentrations of luteinizing hormone and follicle-stimulating hormone were determined. Standard tests with gonadotropin-releasing hormone, thyrotropin-releasing hormone and human chorionic gonadotropin were conducted. Brain magnetic resonance imaging was performed to exclude organic hypothalamic-pituitary lesions. Clinical examination and endocrine investigations revealed hypogonadotropic hypogonadism. Sibutramine induced body weight maintenance as well as improvement in body composition and obesity-related metabolic abnormalities. CONCLUSION: We described the first case of hypogonadotropic hypogonadism in a MC4R homozygous mutation carrier. The potential association between the hormonal disturbance and the hypothalamic derangement caused by the MC4R mutation should be considered. In addition, we demonstrated that sibutramine treatment had a favourable effect on body weight maintenance and obesity-related health risks.

[A new simple method for estimating trunk and visceral fat by bioelectrical impedance: comparison with magnetic resonance imaging and dual X-ray absorptiometry in Czech adolescents]. / Nová jednoduchá metoda stanovení viscerálního a trunkálního tuku pomocí bioelektrické impedance: srovnání s magnetickou rezonancí a duální rentgenovou absorpciometrií u ceských adolescentu.

BACKGROUND: The enlargement of visceral fat (VF) in abdominal obesity is associated with increased cardiometabolic health risks in both adults and adolescents. A precise measurement of VF by sophisticated methods as computed tomography (CT) and magnetic resonance imaging (MRI) cannot be applied in routine clinical practice. The aim of our study was to compare estimates on visceral and trunk fat in adolescents obtained by a new bioimpedance analysis instrument (BIA)--Tanita AB-140 ViScan--with those obtained by MRI, dual X-ray absorptiometry (DEXA) and anthropometry. METHODS AND RESULTS: Investigated cohort: 39 adolescent secondary school students; median (lower quartile; upper quartile)--age: 16.4 (15.4; 17.4) years; body weight: 63.8 (54.1; 79.0) kg; BMI: 21.4 (19.5; 27.4) kg/m2. Investigated parameters: BMI, body circumferences and sagittal abdominal diameter (SAD), trunk, visceral and subcutaneous fat determined by BIA, MRI and DEXA. STATISTICS: Spearman's correlations. The assessment of trunk fat by BIA correlated with DEXA estimates (r = 0.979, p < 0.0001) and with abdominal fat measured by MRI (r = 0.930, p < 0.0001). The visceral fat amount derived from abdominal BIA exhibited lower, however significant correlation with visceral fat determined by MRI (r = 0.791, p < 0.001). The visceral fat area presumed by abdominal BIA significantly correlated with anthropometric parameters as abdominal circumference (r = 0.923, p < 0.0001), waist circumference (r = 0.913, p < 0.0001) and SAD (r= 0.891, p < 0.0001). CONCLUSIONS: The new method estimating abdominal fat by BIA represents a reliable tool for clinical evaluation of the trunk fat in adolescents. However, its advantages over anthropometric measurements in evaluation of VF require further validation studies.

[Genetics of obesity]. / Genetika obezity.

Animal models and family studies led to the identification ofcases of rare monogenic forms of human obesity. Rare Mendelian syndromes as Prader-Willi syndrome and Bardet-Biedl syndrome represent cases of genetically determined obesity. Genome wide linkage and classical candidate gene studies were in general unsuccessful concerning the identification of genes of common obesity. On the other hand, genome-wide association studies (GWAS) were found to be effective, as also variants with only a minor effect have been detected. Seventeen polygenic variants influencing body weight regulation were clearly confirmed. It is assumed that more of these variants exist and therefore they might be identified in near future by GWAS. It is possible that the size effect of some variants can be within few grams of body weight. In order to detect variants with small effect there is a need of meta-analyses based on hundreds of thousands of individuals. Newly identified variants result in an increase of 0.06-0.33 kg/m2 of BMI per allele. In an adult of an average height of 170cm, it corresponds to 173-954 g per risk allele. It was estimated that subjects carrying 13 or more risk alleles were on average 1.46 body mass index units heavier (representing 3.7-4.7 kg) than carriers of less than three risk alleles. Further research should be focused on a gene-gene interaction. An interaction ofgene and environment should be statistically analyzed in adequate proband cohorts. If we are able to identify a large number of risk variants, the predisposition to a certain disease could be predicted. Currently a detailed family history has more predictive power.

Family and population-based studies of variation within the ghrelin receptor locus in relation to measures of obesity.

BACKGROUND: The growth hormone secretagogue receptor (GHSR) is mediating hunger sensation when stimulated by its natural ligand ghrelin. In the present study, we tested the hypothesis that common and rare variation in the GHSR locus are related to increased prevalence of obesity and overweight among Whites. METHODOLOGY/PRINCIPAL FINDINGS: In a population-based study sample of 15,854 unrelated, middle-aged Danes, seven variants were genotyped to capture common variation in an 11 kbp region including GHSR. These were investigated for their individual and haplotypic association with obesity. None of these analyses revealed consistent association with measures of obesity. A -151C/T promoter mutation in the GHSR was found in two unrelated obese patients. One family presented with complete co-segregation, but the other with incomplete co-segregation. The mutation resulted in an increased transcriptional activity (p<0.02) and introduction of a specific binding for Sp-1-like nuclear extracts relative to the wild type. The -151C/T mutation was genotyped in the 15,854 Danes with a minor allele frequency of 0.01%. No association with obesity in carriers (mean BMI: 27+/-4 kg/m(2)) versus non-carriers (mean BMI: 28+/-5 kg/m(2)) (p>0.05) could be shown. CONCLUSIONS/SIGNIFICANCE: In a population-based study sample of 15,854 Danes no association between GHSR genotypes and measures of obesity and overweight was found. Also, analyses of GHSR haplotypes lack consistent associations with obesity related traits. A rare functional GHSR promoter mutation variant was identified, yet there was no consistent relationship with obesity in neither family- nor population-based studies.