Type 2 diabetes mellitus (T2DM) is associated with increased fracture risk; the underlying mechanism remains unexplained. This study aimed to investigate the relationships between body composition and bone and glucose metabolism in postmenopausal women wit h T2DM. Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD) and body composition. A total of 68 postme nopausal women with T2DM and 71 controls were eligible for the study. In contrast to normal BMD in T2DM, a similar prevalence of low-trauma fractures was observed in both groups. T2DM women had significantly higher Trunk fat% and A/G ratio and significantly lower Legs LM% and Legs FM%. Legs LM% was significantly lower in fractured T2DM group and negatively correlated with glycaem ia and HbA1c (p<0.01). Serum osteocalcin was significantly lower in T2DM and inversely correlated with FM%, Trunk FM% and A/G ratio (p<0.01) and positively correlated with Legs FM% and total LM% (p<0.05). In conclusion, abdominal obesity and decrease in mu scle mass may contribute to low bone formation in T2DM women. Further research is needed to unravel underlying pathophysiological mechanisms and to determine whether maintenance of muscle mass, especially in the lower extremities and/or reduction of centra l fat mass can prevent fractures., I. Raška Jr., M. Rašková, V. Zikán, J. Škrha., and Obsahuje bibliografii
Variants within the FTO gene are important determinants of body mass index (BMI), but their role in determination of BMI changes after combined dietary/physical ac tivity intervention is unclear. We have analyzed 107 unrelated overweight non-diabetic Czech females (BMI over 27.5 kg/m2 , age 49.2±12.3 years). FTO variants rs17817449 (first intron) and rs17818902 (third intron) were genotyped. The life style mo dification program (10 weeks) consisted of an age- matched reduction of energy intake and exercise program (aerobic exercise 4 times a week, 60 min each). The mean BMI before intervention was 32.8±4.2 kg/m2 and the mean achieved weight loss was 4.8±3.5 kg (5.3±3.5 %, max. -15.5 kg, min. +2.0 kg, p<0. 01). No significant association between BMI decrease and FTO variants was found. Also waist-to-hip ratio, body composition (body fat, water, active tissue), lipid parameters (total, LDL and HDL cholesterol, triglycerides) glucose and hsCRP change s were independent on FTO variants. FTO variants rs17817449 and rs17818902 are not associated with BMI changes after combined short time dietary/physical activity intervention in overweight females., D. Dlouhá ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
In the present paper we describe changes of anatomical parameters in inbred Lewis strain rats, namely their body weight, body weight gain per week, absolute and relative heart, thyroid gland and skeletal muscle weights, that are assumed to reflect experimentally altered thyroid status. The hyperthyroid state was induced by DL-thyroxine or Na 3,3',5-triiodo-L-thyronine, while methimazole was employed for inducing hypothyroidism. We have found that when compared to euthyroid rats, hypothyroidism resulted in a significantly lower body weight gain, absolute and relative heart weight and, in contrast, in a significant increase of absolute and relative thyroid gland weight. On the other hand, hyperthyroidism led to a significant increase of absolute and relative heart weight and to a significant reduction of absolute and relative thyroid gland weight. However, the body mass was not significantly altered in hyperthyroidism as compared with euthyroid rats. We conclude that our protocol leads to chronic hyper- or hypothyroidism as demonstrated by body, heart and thyroid gland weight changes. These anatomical data can thus be utilized as supplemental criteria for the assessment of the thyroid state of experimental rats., T. Soukup, G. Zachařová, V. Smerdu, I. Jirmanová., and Obsahuje bibliografii
The aim of the current study was to clarify the effect of high sucrose diet (HSD) on bile formation (BF) in rats with hereditary hypertriglyceridemia (HHTg). Potentially positive effects were studied for boldine, a natural choleretic agent. Administration of HSD to HHTg rats led to increased triglyceride deposition in the liver. HSD reduced BF as a consequence of decreased biliary secretion of bile acids (BA) and glutathione. Responsible mechanism was down-regulation of hepatic transporters for BA and glutathione, Bsep and Mrp2, respectively. Moreover, gene expressions of transporters for other constituents of bile, namely Abcg5/8 for cholesterol, Abcb4 for phospholipids, and Oatp1a4 for xenobiotics, were also reduced by HSD. Boldine partially attenuated cholestatic effect of HSD by promotion of biliary secretion of BA through up-regulation of Bsep and Ntcp, and by increase in biliary secretion of glutathione as a consequence of its increased hepatic disposition. This study demonstrates mechanisms of impaired BF during nonalcoholic fatty liver disease induced by HSD. Altered function of responsible transporters suggests also potential for changes in kinetics of drugs, which may complicate pharmacotherapy in subjects with high intake of sucrose, and with fatty liver disease. Sucrose induced alterations in BF may be alleviated by administration of boldine., M. Zagorova, A. Prasnicka, Z. Kadova, E. Dolezelova, L. Kazdova, J. Cermanova, L. Rozkydalova, M. Hroch, J. Mokry, S. Micuda., and Obsahuje bibliografii
The peak bone mass and the rate of bone loss are in part genetically determined. It has been suggested that bone mineral density (BMD) may be related to allelic variation in the apolipoprotein E (ApoE) gene locus. ApoE is important in the receptor-mediated clearance of chylomicron particles from the plasma, Apo E4 having the highest and Apo E2 the lowest receptor affinity. Chylomicrons are the main carrier of vitamin K in the plasma; vitamin K plays an important role in the carboxylation of osteocalcin. We have tested the hypothesis that persons with E4 variant would have lower BMD and increased bone turnover than those with E2 variant. A total of 18 ApoE 2/2 and ApoE 4/4 homozygotes were selected from 873 patients who were examined for the ApoE genotype. BMD in lumbar vertebral, femoral neck and distal forearm was measured and plasma concentrations of osteocalcin and C-terminal fragments of collagen (CTx) were determined. BMD values (expressed as T-score) at the three specified sites were -0.12± 1.72, -0.52± 1.32 and -0.52± 0.81 in ApoE 2/2 group and -0.24± 1.22, 0.00± 0.84 and -0.17± 1.07 in the ApoE 4/4 group. Plasma osteocalcin and CTx were within normal limits in both groups. In conclusion, we did not observe any association of ApoE genotype with BMD and biochemical markers of bone metabolism in ApoE 2/2 and ApoE 4/4 homozygotes., T. Štulc, R. Češka, A. Hořínek, J. Štěpán., and Obsahuje bibliografii
Bone remodeling is a tightly coupled process consisting of repetitive cycles of bone resorption and formation. Both processes are governed by mechanical signals, which operate in conjunction with local and systemic factors in a discrete anatomic structure designated a basic multicellular unit (BMU). The microenvironment around total joint arthroplasty is a dynamic and complex milieu influenced by the chemical and physical stimuli associated with servicing the prosthesis. A key factor limiting the longevity of the prosthesis is polyethylene wear, which induces particle disease, and this may lead to increased and prolonged activity of BMUs resulting in periprosthetic osteolysis. Several pathways regulating BMU function have been reported in the past, including RANKL/RANK/OPG/TRAF6, TNF-α/TNFR/TRAF1, and IL-6/CD126/JAK/STAT. Moreover, the expression and functional activity of all these molecules can be affected by variations in their genes. These may explain the differences in severity of bone defects or prosthetic failure between patients with similar wear rates and the same prosthesis. Simultaneously, this data strongly support the theory of individual susceptibility to prosthetic failure., J. Gallo, M. Raška, F. Mrázek, M. Petřek., and Obsahuje bibliografii a bibliografické odkazy
Bone is a target tissue for hormones, such as the sex steroids, parathormon, vitamin D, calcitonin, glucocorticoids, and thyroid hormones. In the last decade, other “non-classic” hormones that modulate the bone tissue have been identified. While incretins (GIP and GLP-1) inhibit bone remodeling, angiotensin acts to promote remodeling. Bone morphogenetic protein (BMP) has also been found to have anabolic effects on the skeleton by activating bone formation during embryonic development, as well as in the postnatal period of life. Bone has also been identified as an endocrine tissue that produces a number of hormones, that bind to and modulate extra-skeletal receptors. Osteocalcin occupies a central position in this context. It can increase insulin secretion, insulin sensitivity and regulate metabolism of fatty acids. Moreover, osteocalcin also influences phosphate metabolism via osteocyte-derived FGF23 (which targets the kidneys and parathyroid glands to control phosphate reabsorption and metabolism of vitamin D). Finally, osteocalcin stimulates testosterone synthesis in Leydig cells and thus may play some role in male fertility. Further studies are necessary to confirm clinically important roles for skeletal tissue in systemic regulations., I. Zofkova., and Obsahuje bibliografii