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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leptin is a hormone involved with satiety and energy balance and proposed to be an anti-obesity factor. Much effort has been dedicated to the relationship between leptin and bone. This interest stems from the knowledge that body weight is a major determinant of bone density. It is known that obese persons have stronger bones and lose bone tissue at a slower pace. Therefore, attention has been given to leptin as a mediator of increased osteogenesis. Leptin has been shown to play a role on bone both in vitro and in vivo. The administration of leptin in vitro induced the expression of leptin receptors on stromal cells, the differentiation to osteoblasts and inhibition of differentiation into the adipocyte phenotype. In addition, leptin was able to inhibit osteoclastogenesis of peripheral blood mononuclear cells. Therefore, there is in vitro and experimental evidence that leptin is able both to stimulate osteoblasts and inhibit osteoclast differentiation. This would be in line with the hypothesis that the correlation between obesity and increased BMD is linked to leptin activity. However, experimental results are indicative of a role of CNS in mediating the effect of leptin on bone metabolism. These effects are opposite to the direct effects on bone cells and lead to bone loss. To solve the problem, it has been suggested that obese individuals have a resistance of nervous structures to leptin. In chronic renal failure serum leptin levels are markedly increased. An inverse correlation between histomorphometric parameters of bone turnover and serum leptin levels and between leptin and PTH have been reported. Therefore, the hypothesis has been raised that leptin lowers bone turnover in chronic renal failure. Since leptin has a direct stimulatory effect on bone and an indirect opposite effect via the CNS, it has been suggested that in CRF a resistance of nervous structures to leptin, like in obesity, may be present. By now, coherent findings suggest that the prevailing effect of leptin on bone in ESRD is that of reducing bone turnover.
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PMID:Leptin and bone metabolism. 1529 17

Adipose tissue is now considered an important system operating strictly in concert with other systems. The adipocyte is the main producer of two pleiotropic compounds, leptin and adiponectin, modulating inflammation and having multiple effects in disparate organs including the cardiovascular and the central nervous system. Leptin has disparate influences on various physiologic and organ systems including glucose homeostasis, hematopoiesis and the reproductive and cardiovascular systems and is a crucial hormone for the regulation of food intake and body weight. Peripherally, leptin modulates insulin sensitivity and high leptin triggers insulin resistance and vice versa. Obesity, a situation where circulating leptin attains very high levels is accompanied by increased bone mass, a phenomenon which may depend on direct stimulation of osteoblasts by leptin. However in animal models the stimulating effect of leptin on the osteoblast is counterbalanced by a strong inhibitor effect on bone formation in the central nervous system. Two recent studies reported an inverse link between leptin, bone mass and PTH in dialysis patients suggesting that leptin may be implicated in low bone turnover in these patients, likely by a mechanism involving the central nervous system. Leptin induces vascular calcifications in vitro. In uremic man leptin is unrelated to valvular calcifications but predicts incident cardiovascular events in overweight and obese dialysis patients. Leptin seems to be a relevant player in the emerging connection between bone and cardiovascular alterations in patients with end stage renal disease.
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PMID:Leptin in end stage renal disease (ESRD): a link between fat mass, bone and the cardiovascular system. 1624 56

Patients with primary hyperparathyroidism (PHPT) have impaired vasodilation both dependent and independent of endothelium. The aims of our study were to measure three different biochemical markers of endothelial activation, i. e., plasma thrombomodulin, soluble(s) E-selectin, and von Willebrand factor, in PHPT patients before and one year after successful parathyroidectomy, and to distinguish the potential effect of hypercalcemia and/or high parathyroid hormone from that of major cardiovascular risk factors (diabetes mellitus, hyperlipidemia, hypertension, obesity, smoking habit) on endothelial function. Twenty consecutive patients with PHPT subdivided into two groups according to the absence (n = 8) or presence (n = 12) of one or more risk factors, and fifteen healthy normocalcemic subjects were studied. Baseline thrombomodulin levels were similar in the groups with and without risk factors, and in controls. In contrast, sE-selectin and von Willebrand factor were higher in PHPT patients with risk factors than in those without risk factors (p < 0.05 and p < 0.01, respectively) and controls (p < 0.01). Neither thrombomodulin nor sE-selectin changed after parathyroidectomy in either PHPT group. Plasma von Willebrand factor decreased (p < 0.01) in patients without risk factors, while persisting at high levels in patients with risk factors. In conclusion, in spite of a limitation due to the small number of patients, our study suggests that classic cardiovascular risk factors seem to be the main determinants for the high plasma levels of sE-selectin and vWF in PHPT. Together with unaltered thrombomodulin and sE-selectin levels, a plasma vWF decrease after parathyroidectomy might reflect a specific mechanism of its endothelial calcium- and/or PTH-stimulated secretion in some PHPT patients without risk factors. Whether a vWF reduction after parathyroidectomy may be used as a biochemical index for improved endothelial function in PHPT patients without risk factors has yet to be demonstrated in larger studies.
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PMID:Biochemical markers of endothelial activation in primary hyperparathyroidism. 1652 14

Obesity represents one of serious risk factors in chronic renal failure patients (CRF). In three years prospective double-blind randomised multicentre study we monitored 66 patients with advanced chronic renal insufficiency, GFR 24.4-37.3 ml/min (0.41 to 0.62 ml/s) and BMI > or = 30 kg/m2 on long term low-protein diet (0.6 P/kg BW/day) and ACEI + ARB. Thirty four randomly selected patients (group I) were treated with keto amino acids, 32 patients in control group (group II) with placebo. During the study period significant decrease of BMI, proteinuria and slowing in progression of renal failure (C(in)) were found. Significant changes were also noted in parameters of albumin and transferrin (p < 0.02), leucin and WQ (p < 0.01 - p < 0.02), glycaemia and HbA1c (p < 0.02), triglycerides (p < 0.01), leptin and ObRe (p < 0.01) and selected parameters of endothelial dysfunction (ET1, p < 0.02, TGFbeta1, p < 0.02). Significantly also decreased PTH value (p < 0.01). Successful treatment of obesity can significantly improve long term prognosis in CRF patients.
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PMID:[Obesity and progression of chronic renal insufficiency: a Czech long term prospective double-blind randomised multicentre study]. 1687 60

Several studies showed that carotid atherosclerosis and stiffness are independent prognostic factors of cardiovascular morbidity and mortality in the general population and in end-stage renal disease patients. However, the impact of established risk factors on carotid structural and elastic properties in non-diabetic elderly hemodialysis patients with negative history for cardiovascular disease has not been fully elucidated. In this paper, we investigated the effect of established and potential risk factors on carotid atherosclerosis and stiffness. Thirty stable, non-symptomatic, non-diabetic patients, aged 65-years and older (mean age 71.4+/-4.15, range 65-79) on hemodialysis for more than 6 months, were included. All patients underwent B-mode ultrasonography of common carotid artery estimating intima-media wall thickness and wall-to-lumen ratio bilaterally and checking for the presence of plaques. Carotid elasticity was evaluated by compliance, distensibility, and the incremental elastic modulus (Einc), whereas systemic arterial stiffening was evaluated by the augmentation index provided by tonometry of radial artery. Our results showed that presence of carotid plaques and wall thickening were frequent findings in this population (76% and 73.3%, respectively) and they were positively associated with fibrinogen (P<0.005), diastolic blood pressure (P<0.004), visceral obesity (P<0.001) and bio-intact PTH (i-PTH) (P=0.03). Overall, systemic and carotid stiffness were strongly correlated with hs-CRP (P=0.018), serum ferritin (P=0.02) with age (P=0.03), lipids (P=0.03) and i-PTH (P=0.05). In conclusion, our findings show that stiffening and atherosclerosis in non-symptomatic elderly HD patients are very common and they are related not only to hemodynamic changes (diastolic blood pressure), inflammation (hs-CRP, fibrinogen, ferritin) or metabolic dysfunction (increased i-PTH, abnormal lipid profile), but also to abnormal fat deposition (increased waist to hip ratio and waist circumference). Considering the high morbidity and mortality of elderly patients, close monitoring of these parameters could be useful to prevent cardiovascular events.
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PMID:Atherosclerotic risk factors and carotid stiffness in elderly asymptomatic HD patients. 1708 15

Pseudohypoparathyroidism type Ia (PHP-Ia) is characterized by Albright's hereditary osteodistrophy (AHO) and resistance to hormones that act via the alpha subunit of the Gs protein (Gsalpha) protein, ie PTH, TSH, FSH/LH, and, as recently described in limited series, GHRH. However, the current lack of data on GHRH secretion, obesity and short stature included in the AHO phenotype hampers interpretation of GH secretory status and its effects on these subjects. We evaluated GH secretion after GHRH plus arginine (Arg) stimulus, IGF-I levels and anthropometric features in an exclusively pediatric population of 10 PHP-Ia subjects. Of our PHP-Ia children, 5 out of 10 (50%) showed impaired GH responsiveness to the provocative test, with a lower prevalence than the 75-100% previously reported. A negative correlation (p=0.024) was found between GH secretion and body mass index (BMI), whereas no correlation emerged between GH and IGF-I values (p=0.948). Height and growth velocity did not significantly differ between GH-deficient and GH-sufficient subjects. In the 5 GH-deficient patients, GHRH resistance could arguably be responsible for hormonal impairment; however, 3 of them were obese, showing normal stature and IGF-I levels: the increased BMI in these subjects could influence GH secretion and its effects. In conclusion, GH deficiency is frequent among PHP-Ia children and its prevalence is variable, two factors indicating that GH secretory testing should be part of the routine management of this patient group. It could be argued that GHRH resistance is the pathogenetic mechanism in most patients, but further studies on GHRH secretion are needed to define which values can be considered as raised. Lastly, because BMI has been indicated as a major determinant of evoked adult GH response to provocative testing, GH levels related to increased BMI also in childhood could be helpful in defining GH assessment in obese or overweight PHP-Ia children.
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PMID:GH secretion in a cohort of children with pseudohypoparathyroidism type Ia. 1739 98

Inbred albino Louvain (LOU) rats are considered a model of healthy aging due to their increased longevity in the absence of obesity and with a low incidence of common age-related diseases. In this study, we characterized the bone phenotype of male and female LOU rats at 4, 20 and 27 months of age using quantitative micro computed tomographic (mCT) imaging, histology and biochemical analysis of circulating bone biomarkers. Bone quality and morphometry of the distal femora, assessed by mCT, was similar in male and female rats at 4 months of age and deteriorated over time. Histochemical staining of undecalcified bone showed a significant reduction in cortical and trabecular bone by 20 months of age. The reduction in mineralized tissue was accompanied by reduced numbers of osteoblasts and osteoclasts and a significant increase in marrow adiposity. Biochemical markers of bone turnover, C-telopeptide and osteocalcin, correlated with the age-related bone loss whereas the calciotropic hormones PTH and vitamin D remained unchanged over time. In summary, aged LOU rats exhibit low-turnover bone loss and marrow fat infiltration, which are the hallmarks of senile osteoporosis, and thus represent a novel model in which to study the molecular mechanisms leading to this disorder.
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PMID:Age-related bone loss in the LOU/c rat model of healthy ageing. 1899 16

Albright hereditary osteodystrophy (AHO), also known as Martin-Albright syndrome (MAS), is a rare autosomal dominantly transmitted disease characterized by short stature, obesity, mental retardation, a round facies, and brachymetacarpia and -tarsia, as well as cutaneous calcification. The disease is caused by mutations in the GNAS gene localized on chromosome 20q13.2 encoding for an adenyl-cyclase-stimulating protein (Gsalpha). A 58-year-old patient presented with small stature since childhood, moderate mental retardation, round facies and soft tissue masses on the thighs. A biopsy of the latter showed subcutaneous ossification. Laboratory results showed hypocalcemia, as well as increased plasma levels of PTH and calcitonin. The clinical diagnosis was confirmed by detection of reduced activity of Gsalpha. In patients with cutaneous calcification and disturbed calcium metabolism, AHO is an important differential diagnostic consideration.
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PMID:First diagnosis of Martin-Albright syndrome in a 58-year-old patient. 1913 95

Vitamin D insufficiency/deficiency has been worldwide reported in all age groups in recent years. It has been considered a Public Health matter since decreased levels of vitamin D has been related to several chronic diseases, as type 2 diabetes mellitus (T2DM), obesity and hypertension. Glucose intolerance and insulin secretion has been observed during vitamin D deficiency, both in animals and humans resulting in T2DM. The supposed mechanism underlying these findings is presence of vitamin D receptor in several tissues and cells, including pancreatic beta-cells, adipocyte and muscle cells. In obese individuals, the impaired vitamin D endocrine system, characterized by high levels of PTH and 1,25(OH)(2)D(3) could induce a negative feedback for the hepatic synthesis of 25(OH)D and also contribute to a higher intracellular calcium, which in turn secrete less insulin and deteriorate insulin sensitivity. In hypertension, vitamin D could act on renin-angiotensin system and also in vascular function. Administration of 1,25(OH)(2)D(3) could decreases renin gene expression and inhibit vascular smooth muscle cell proliferation. However, prospective and intervention human studies that clearly demonstrates the benefits of vitamin D status adequacy in the prevention and treatment of endocrine metabolic diseases are lacking. Further research still necessary to assure the maximum benefit of vitamin D in such situations.
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PMID:[Vitamin D and endocrine diseases]. 1976 53

Albright hereditary osteodystrophy (AHO) is a syndrome of short stature, obesity, brachydactyly and subcutaneous calcifications with pseudohypoparathyroidism (PHP; leading to hypocalcaemia, hyperphosphataemia and elevated levels of parathyroid hormone, PTH). It was first described over 60 years ago. Since then, much has been learned about the aetiology of AHO which has been shown to be caused by heterozygous loss-of-function mutations within the GNAS1 gene. GNAS1 is subject to imprinting leading to phenotypic heterogeneity within kindreds with one mutation. Patients with AHO often present with symptoms of hypocalcaemia and/or with subcutaneous calcifications. The latter is thought to be the typical skin abnormality in AHO. We describe a family with AHO and hormone resistance (PHP type Ia) resulting from a rare mutation in GNAS1. The proband presented with small subcutaneous calcifications in the helix of the right ear and concentrated in a sharply demarcated zone of subcutaneous and dermal hypoplasia. This abnormality has so far not been described in patients with AHO. We speculate on the mechanism of dermal hypoplasia and resistance to PTH and suggest that subcutanous or dermal hypoplasia might be another feature which can be present in patients with AHO.
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PMID:Unique skin changes in a case of Albright hereditary osteodystrophy caused by a rare GNAS1 mutation. 1986 4


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