Allelic variations in the vitamin D receptor gene, insulin secretion and parents' heights are independently associated with height in obese children and adolescents

Polymorphisms in the VDR gene were reported to be associated with variations in intrauterine and postnatal growth and with adult height, but also with other traits that are strongly correlated such as the BMI, insulin sensitivity, insulin secretion and hyperglycemia. Here, we assessed the impact of VDR polymorphisms on body height and its interactions with obesity- and glucose tolerance-related traits in obese children and adolescents. We studied 173 prepubertal (Tanner's stage 1) and 146 pubertal (Tanner's stages 2-5) obese children who were referred for a weight-loss program. Three single nucleotide polymorphisms were genotyped: rs1544410 (BsmI), rs7975232 (ApaI) and rs731236 (TaqI). BsmI and TaqI genotypes were significantly associated with height in pubertal children, but the associations did not reach statistical significance in prepubertal children. In stepwise regression analyses, the lean body mass, insulin secretion, BsmI or TaqI genotypes and the father's and the mother's height were independently and positively associated with height in pubertal children. These covariables accounted for 46% of the trait variance. The height of homozygous carriers of the minor allele of BsmI was 0.65 z-scores (4 cm) higher than the height of homozygous carriers of the major allele (P=.0006). Haplotype analyses confirmed the associations of the minor alleles of BsmI and TaqI with increased height. In conclusion, VDR genotypes were significantly associated with height in pubertal obese children. The associations were independent from the effects of confounding traits, such as the body fat mass, insulin secretion, insulin sensitivity and glucose tolerance. (C) 2012 Elsevier Inc. All rights reserved.

Migrant labor and wear-out in manual sugarcane harvesting in Sao Paulo, Brazil

The scope of this paper is to describe the work of manual sugarcane harvesters, assessing the nutritional behavior and body composition between the beginning and the end of the harvest. A descriptive longitudinal study was made of harvesters in Piracicaba, Sao Paulo, Brazil, who answered a socio-demographic questionnaire and authorized measurement of Body Mass Index, Body Fat Percentage and Arm Muscle Circumference at three stages. Creatine kinase on the skeletal isoform, C-reactive protein and plasma urea were measured at the end of the harvest. Thirty male migrant harvesters with ages ranging from 18 to 44 from the Northeast (Ceara) were assessed over a nine-month period. The workers suffered significant body fat and weight loss in the first half of the harvest. Eighteen workers had abnormal levels of creatine kinase and four - out of 24 who had donated blood - had altered urea levels. Sugarcane harvesting work causes weight and body fat loss and gains in the lean body mass index, which suffers wear-out when working on consecutive harvests. It can also cause changes in biochemical markers of chronic systemic inflammation. Further studies will make it possible to comprehend the relationships between stress, wear-out, labor longevity and health in sugarcane harvesting.

Do patients with osteogenesis imperfecta need individualized nutritional support?

Objective: Information regarding nutrition and body composition in patients diagnosed with osteogenesis imperfecta (OI) is scarce. In the present study, nutritional status, bone mineral density, and biochemical parameters of subjects with Of were evaluated. Methods: Patients with type I OI (n = 13) and type III OI (n = 13) and healthy controls (n = 8) were selected. Nutritional status and bone mineral density were assessed by a 3-d food diary and dual-energy X-ray absorptiometry at the lumbar spine, respectively. Body mass index, serum albumin, calcium, creatinine, cross-linked C-telopeptide, parathyroid hormone, and 25-hydroxivitamin D-3 were also evaluated. Results: Patients with OI had lower bone mineral density (P < 0.05 versus controls). Patients with type III OI had the highest body mass index (P < 0.05 versus patients with type I OI and controls) and the lowest lean body mass (P < 0.05 versus patients with type I OI and controls). In patients with OI, the number of fractures was positively correlated with body mass index (r = 0.581, P = 0.002) and the percentage of body fat (r = 0.451, P = 0.027) and negatively correlated to lean body mass (r = -0.523, P = 0.009). Even when taking dietary supplements, 58% and 12% of subjects with OI did not achieve the calcium and vitamin D recommendations, respectively. Conclusions: Body composition is a risk factor for bone fractures in subjects with OI. Individualized nutritional support is recommended not only to improve body composition but also to potentiate pharmacologic and physical therapies. (C) 2012 Elsevier Inc. All rights reserved.

Hypermetabolism and altered substrate oxidation in HIV-infected patients with lipodystrophy

Objective: Human immunodeficiency virus type 1 (HIV)-associated lipodystrophy syndrome compromises body composition and produces metabolic alterations, such as dyslipidemia and insulin resistance. This study aims to determine whether energy expenditure and substrate oxidation are altered due to human HIV-associated lipodystrophy syndrome. Methods: We compared energy expenditure and substrate oxidation in 10 HIV-infected men with lipodystrophy syndrome (HIV+LIPO+), 22 HIV-infected men without lipodystrophy syndrome (HIV+LIPO-), and 12 healthy controls. Energy expenditure and substrate oxidation were assessed by indirect calorimetry, and body composition was assessed by dual-energy X-ray absorptiometry. The substrate oxidation assessments were performed during fasting and 30 min after eucaloric breakfast consumption (300 kcal). Results: The resting energy expenditure adjusted for lean body mass was significantly higher in the HIV+LIPO+ group than in the healthy controls (P = 0.02). HIV-infected patients had increased carbohydrate oxidation and lower lipid oxidation when compared to the control group (P < 0.05) during fasting conditions. After the consumption of a eucaloric breakfast, there was a significant increase in carbohydrate oxidation only in the HIV+LIPO- and control groups (P < 0.05), but there was no increase in the HIV+LIPO+ group. Conclusion: Hypermetabolism and alteration in substrate oxidation were observed in the HIV+LIPO+ group. (C)2012 Elsevier Inc. All rights reserved.

Migrant labor and wear-out in manual sugarcane harvesting in São Paulo, Brazil

The scope of this paper is to describe the work of manual sugarcane harvesters, assessing the nutritional behavior and body composition between the beginning and the end of the harvest. A descriptive longitudinal study was made of harvesters in Piracicaba, São Paulo, Brazil, who answered a socio-demographic questionnaire and authorized measurement of Body Mass Index, Body Fat Percentage and Arm Muscle Circumference at three stages. Creatine kinase on the skeletal isoform, C-reactive protein and plasma urea were measured at the end of the harvest. Thirty male migrant harvesters with ages ranging from 18 to 44 from the Northeast (Ceará) were assessed over a nine-month period. The workers suffered significant body fat and weight loss in the first half of the harvest. Eighteen workers had abnormal levels of creatine kinase and four - out of 24 who had donated blood - had altered urea levels. Sugarcane harvesting work causes weight and body fat loss and gains in the lean body mass index, which suffers wear-out when working on consecutive harvests. It can also cause changes in biochemical markers of chronic systemic inflammation. Further studies will make it possible to comprehend the relationships between stress, wear-out, labor longevity and health in sugarcane harvesting.

Loss of the anorexic response to systemic 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside administration despite reducing hypothalamic AMP-activated protein kinase phosphorylation in insulin-deficient rats

This study tested whether chronic systemic administration of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) could attenuate hyperphagia, reduce lean and fat mass losses, and improve whole-body energy homeostasis in insulin-deficient rats. Male Wistar rats were first rendered diabetic through streptozotocin (STZ) administration and then intraperitoneally injected with AICAR for 7 consecutive days. Food and water intake, ambulatory activity, and energy expenditure were assessed at the end of the AICAR-treatment period. Blood was collected for circulating leptin measurement and the hypothalami were extracted for the determination of suppressor of cytokine signaling 3 (SOCS3) content, as well as the content and phosphorylation of AMP-kinase (AMPK), acetyl-CoA carboxylase (ACC), and the signal transducer and activator of transcription 3 (STAT3). Rats were thoroughly dissected for adiposity and lean body mass (LBM) determinations. In non-diabetic rats, despite reducing adiposity, AICAR increased (∼1.7-fold) circulating leptin and reduced hypothalamic SOCS3 content and food intake by 67% and 25%, respectively. The anorexic effect of AICAR was lost in diabetic rats, even though hypothalamic AMPK and ACC phosphorylation markedly decreased in these animals. Importantly, hypothalamic SOCS3 and STAT3 levels remained elevated and reduced, respectively, after treatment of insulin-deficient rats with AICAR. Diabetic rats were lethargic and displayed marked losses of fat and LBM. AICAR treatment increased ambulatory activity and whole-body energy expenditure while also attenuating diabetes-induced fat and LBM losses. In conclusion, AICAR did not reverse hyperphagia, but it promoted anti-catabolic effects on skeletal muscle and fat, enhanced spontaneous physical activity, and improved the ability of rats to cope with the diabetes-induced dysfunctional alterations in glucose metabolism and whole-body energy homeostasis.

Serum free testosterone, leptin and soluble leptin receptor changes in a 6-week strength-training programme

[EN] Strength training is usually associated with a reduction in fat mass and with muscle hypertrophy. The aim of the present study was to examine whether the serum free leptin index (FLI), measured by the molar excess of soluble leptin receptor (sOB-R) over leptin, is increased by 6 weeks of strength training. Eighteen male, physical education students were randomly assigned to two groups: a strength-training (n 12) and a control group (n 6). Body composition (lean body mass and body fat) determined by dual-energy X-ray absorptiometry (DXA), muscle performance and leptin, sOB-R, total testosterone and free testosterone concentrations were determined before and after training. Fat mass was reduced by 1 kg with strength training (P<0.05). Lean body mass of trained extremities was increased by 3% (P<0.05), while the concentration of free testosterone in serum was reduced by 17% (P<0.05) after training. However, despite the reduction in fat mass and free testosterone, serum leptin concentration was not significantly affected by strength training, even after accounting for the differences in body fat. By contrast, for a given fat mass, the sOB-R was increased by 13% (P<0.05) at the end of the strength-training programme, although the molar excess of sOB-R over leptin remained unchanged. Therefore, the quantity of free leptin available to bind to the target tissues was not significantly affected by the short strength-training programme, which elicited a 7% reduction in fat mass.

Exercise associated factors affecting cardiovascular health and function: from myocyte signaling to genetic variations

The exact mechanisms of the exercise induced adaptations is not lucid, but recent studies have delineated two means of signaling by which the adaptations occur (1) substrate availability signaling (metabolic stress) (2) hormone-receptor signaling. We have decided to specifically investigate two metabolic signaling enzymes [AMP-activated kinase (AMPK) and Sirtuin 1(SIRT1)] and two hormones [Adiponectin and Adrenergic stimulation].Tis based on four papers with the following conclusions: (1)Increase in SIRT1 activity and expression in H9c2 cells treated with phenylephrine is an adaptive response to the hypertrophic stress, mediated by AMPK. (2)The lack of optimal nutritional conditions (energetic substrates) due to a prolonged activation of AMPK can contrast the establishment of hypertrophy, possibly also by means of the negative modulation of ODC activity. (3) Our findings offer a possibile hypothesis as to the fact the the G allele on site 45 could lead to the increasd risk of Type II diabetes through a decrease in lean body mass. (4) Our results suggest that there is an ADIPOQ gene effect in relation to bone parameters. Statistical analysis show that the presence of the T allele in position 45 favors an increase in lumbar spine bone mineral content (BMC) when compared to subjects with a G allele substitution, which can be do the the increase in lean body mass in this genotype group.

Effetti della somministrazione di Testosterone in donne

Come noto, il testosterone (T) gioca un ruolo importante in differenti funzioni fisiologiche. Il ruolo del T nelle donne è tuttavia largamente sconosciuto. Recenti studi riportano un ruolo del T nella modulazione della funzionalità sessuale femminile. SCOPO: Indagare gli effetti del T nelle donne, su parametri metabolici, ossei e composizione corporea e studiare gli effetti del T sulla proliferazione e innervazione della vagina. METODI: 16 soggetti FtM ovariectomizzati sono stati sottoposti a terapia con TU 1000 mg im + placebo o dutasteride. Alla settimana 0 e 54 sono stati valutati: parametri metabolici e composizione corporea. 16 campioni di tessuto vaginale ottenuti da soggetti FtM trattati con T, 16 donne PrM e 16 donne M sono stati analizzati. Sono stati valutati: morfologia, contenuto di glicogeno, espressione del Ki-67, recettori per estrogeni e androgeni ed innervazione. RISULTATI: La somministrazione di T in soggetti FtM determina aumento del colesterolo LDL e riduzione delle HDL. L’HOMA si riduce significativamente nel gruppo TU e tende ad aumentare nel gruppo TU+D. L’ematocrito aumenta. BMI, WHR e grasso tendono a ridursi, la massa magra ad aumentare. Non riportiamo cambiamenti del metabolismo osseo. Nel tessuto vaginale di FtM osserviamo perdita della normale architettura dell’epitelio. La somministrazione di T determina riduzione della proliferazione cellulare. I recettori per E e il PGP 9.5 sono significativamente ridotti nei FtM. La presenza di recettori per A è dimostrata nello stroma e nell’epitelio. L’espressione di AR si riduce con l’età e non cambia con la terapia con T nella mucosa, mentre aumenta nello stroma dopo somministrazione di T. CONCLUSIONI: Non riportiamo effetti avversi maggiori dopo somministrazione di T. La terapia con T determina ridotta proliferazione dell’epitelio vaginale. I recettori per AR sono presenti sia nello stroma che nell’epitelio. T aumenta l’espressione di AR nello stroma.

Standardized protocol for a depletion of intramyocellular lipids (IMCL)

Intramyocellular lipids (IMCL) are flexible fuel stores that are depleted by physical exercise and replenished by fat intake. IMCL or their degradation products are thought to interfere with insulin signaling thereby contributing to insulin resistance. From a practical point of view it is desirable to deplete IMCL prior to replenishing them. So far, it is not clear for how long and at which intensity subjects have to exercise in order to deplete IMCL. We therefore aimed at developing a standardized exercise protocol that is applicable to subjects over a broad range of exercise capacity and insulin sensitivity and allows measuring reliably reduced IMCL levels.Twelve male subjects, including four diabetes type 2 patients, with wide ranges of exercise capacity (VO(2)peak per total body weight 27.9-55.8 ml x kg(-1) x min(-1)), insulin sensitivity (glucose infusion rate per lean body mass 4.7-15.3 mg x min(-1) x kg(-1)), and BMI (21.7-31.5 kg x m(-2)), respectively, were enrolled. Using (1)H magnetic resonance spectroscopy ((1)H-MRS), IMCL was measured in m.tibialis anterior and m.vastus intermedius before and during a depletion protocol of a week, consisting of a moderate additional physical activity (1 h daily at 60% VO(2)peak) and modest low-fat (10-15%) diet.Absolute IMCL-levels were significantly reduced in both muscles during the first 3 days and stayed constant for the next 3 days of an identical diet/exercise-scheme. These reduced IMCL levels were independent of insulin sensitivity, yet a tendency to lower depleted IMCL levels has been observed in subjects with higher VO(2)peak.The proposed protocol is feasible in subjects with large differences in exercise capacity, insulin sensitivity, and BMI, leading to reduced IMCL levels that neither depend on the exact duration of the depletion protocol nor on insulin sensitivity. This allows for a standardized preparation of IMCL levels either for correlation with other physiological parameters or for replenishment studies.

Biologically relevant sex differences for fitness-related parameters in active octogenarians

The number of elderly people is growing in western populations, but only few maximal performance data exist for people >75 years, in particular for European octogenarians. This study was performed to characterize maximal performance of 55 independently living subjects (32 women, 81.1 +/- 3.4 years; 23 men, 81.7 +/- 2.9 years) with a focus on sex differences. Maximal performance was determined in a ramp test to exhaustion on a bicycle ergometer with ergospirometry, electrocardiogram and blood lactate measurements. Maximal isometric extension strength of the legs (MEL) was measured on a force platform in a seated position. Body composition was quantified by X-ray absorptiometry. In >25% of the subjects, serious cardiac abnormalities were detected during the ramp test with men more frequently being affected than women. Maximal oxygen consumption and power output were 18.2 +/- 3.2 versus 25.9 +/- 5.9 ml min(-1) kg(-1) and 66 +/- 12 versus 138 +/- 40 W for women versus men, with a significant sex difference for both parameters. Men outperformed women for MEL with 19.0 +/- 3.8 versus 13.6 +/- 3.3 N kg(-1). Concomitantly, we found a higher proportion of whole body fat in women (32.1 +/- 6.2%) compared to men (20.5 +/- 4.4%). Our study extends previously available maximal performance data for endurance and strength to independently living European octogenarians. As all sex-related differences were still apparent after normalization to lean body mass, it is concluded that it is essential to differentiate between female and male subjects when considering maximal performance parameters in the oldest segment of our population.

[Calculating the basal metabolic rate and severe and morbid obesity]

The aim of this study was to evaluate the currently available predictive equations for basal metabolic rate (BMR) in subjects with obesity class II and III, and to assess the contribution by the components of a two-compartment model of body composition, namely the lean body mass (LBM) and the fat mass (FM) to the prediction. A second objective was to examine the reliability of the Harris Benedict equation in obese subjects, especially with a weight > or = 120 kg.

Effects of growth hormone (GH) replacement therapy on very low density lipoprotein apolipoprotein B100 kinetics in patients with adult GH deficiency: a stable isotope study

Patients with adult GH deficiency are often dyslipidemic and may have an increased risk of cardiovascular disease. The secretion and clearance of very low density lipoprotein apolipoprotein B 100 (VLDL apoB) are important determinants of plasma lipid concentrations. This study examined the effect of GH replacement therapy on VLDL apoB metabolism using a stable isotope turnover technique. VLDL apoB kinetics were determined in 14 adult patients with GH deficiency before and after 3 months GH or placebo treatment in a randomized double blind, placebo-controlled study using a primed constant [1-(13)C]leucine infusion. VLDL apoB enrichment was determined by gas chromatography-mass spectrometry. GH replacement therapy increased plasma insulin-like growth factor I concentrations 2.9 +/- 0.5-fold (P < 0.001), fasting insulin concentrations 1.8 +/- 0.6-fold (P < 0.04), and hemoglobin A1C from 5.0 +/- 0.2% to 5.3 +/- 0.2% (mean +/- SEM; P < 0.001). It decreased fat mass by 3.4 +/- 1.3 kg (P < 0.05) and increased lean body mass by 3.5 +/- 0.8 kg (P < 0.01). The total cholesterol concentration (P < 0.02), the low density lipoprotein cholesterol concentration (P < 0.02), and the VLDL cholesterol/VLDL apoB ratio (P < 0.005) decreased. GH therapy did not significantly change the VLDL apoB pool size, but increased the VLDL apoB secretion rate from 9.2 +/- 2.0 to 25.9 +/- 10.3 mg/kg x day (P < 0.01) and the MCR from 11.5 +/- 2.7 to 20.3 +/- 3.2 mL/min (P < 0.03). No significant changes were observed in the placebo group. This study suggests that GH replacement therapy improves lipid profile by increasing the removal of VLDL apoB. Although GH therapy stimulates VLDL apoB secretion, this is offset by the increase in the VLDL apoB clearance rate, which we postulate is due to its effects in up-regulating low density lipoprotein receptors and modifying VLDL composition.

The consequences of growth hormone deficiency in adulthood, and the effects of growth hormone replacement

The availability of recombinant human growth hormone (GH) has resulted in investigation of the role of GH in adulthood and the effects of GH replacement in the GH-deficient adult. These studies have led to the recognition of a specific syndrome of GH-deficiency, characterized by symptoms, signs and investigative findings. Adults with long-standing growth hormone deficiency are often overweight, have altered body composition, with reduced lean body mass (LBM), increased fat mass (FM), reduced total body water and reduced bone mass. In addition, there is reduced physical and cardiac performance, altered substrate metabolism and an abnormal lipid profile predisposing to the development of cardiovascular disease. Adults with GH deficiency report reduced psychological well-being and quality of life. These changes may contribute to the morbidity and premature mortality observed in hypopituitary adults on conventional replacement therapy. GH treatment restores LBM, reduces FM, increases total body water and increases bone mass. Following GH therapy, increases are recorded in exercise capacity and protein synthesis, and "favourable" alterations occur in plasma lipids. In addition, psychological well-being and quality of life improve with replacement therapy. GH is well tolerated; adverse effects are largely related to fluid retention and respond to dose adjustment. It is likely that GH replacement will become standard therapy for the hypopituitary adult in the near future. The benefits of GH replacement in the GH-deficient adult have been unequivocally demonstrated in studies lasting up to 3 years. The results of longer term studies are awaited to determine whether these benefits are sustained over a lifetime.

Identification of a SIRT1 mutation in a family with type 1 diabetes.

Type 1 diabetes is caused by autoimmune-mediated β cell destruction leading to insulin deficiency. The histone deacetylase SIRT1 plays an essential role in modulating several age-related diseases. Here we describe a family carrying a mutation in the SIRT1 gene, in which all five affected members developed an autoimmune disorder: four developed type 1 diabetes, and one developed ulcerative colitis. Initially, a 26-year-old man was diagnosed with the typical features of type 1 diabetes, including lean body mass, autoantibodies, T cell reactivity to β cell antigens, and a rapid dependence on insulin. Direct and exome sequencing identified the presence of a T-to-C exchange in exon 1 of SIRT1, corresponding to a leucine-to-proline mutation at residue 107. Expression of SIRT1-L107P in insulin-producing cells resulted in overproduction of nitric oxide, cytokines, and chemokines. These observations identify a role for SIRT1 in human autoimmunity and unveil a monogenic form of type 1 diabetes.