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Recent advances in the understanding of the molecular basis of genetic lipodystrophies have promoted understanding of how adipose tissue disorders can cause the metabolic syndrome and its complications. These discoveries hold promise for elucidating pathways and mechanisms by which common disorders of obesity cause metabolic complications. Novel therapeutic approaches for patients with lipodystrophies also may have implications for treatment of the metabolic syndrome in patients with regional adiposity. This article reviews these recent advances in our knowledge of the clinical features, metabolic abnormalities, and pathogenetic or other bases of various types of lipodystrophies. 相似文献
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Xavier Prieur Cedric Le May Jocelyne Magré Bertrand Cariou 《Current atherosclerosis reports》2014,16(9):1-11
Lipodystrophies are rare acquired and genetic disorders characterized by the selective loss of adipose tissue. One key metabolic feature of patients with congenital inherited lipodystrophy is hypertriglyceridemia. The precise mechanisms by which the lack of adipose tissue causes dyslipidemia remain largely unknown. In recent years, new insights have arisen from data obtained in vitro in adipocytes, yeast, drosophila, and very recently in several genetically modified mouse models of generalized lipodystrophy. A common metabolic pathway involving accelerated lipolysis and defective energy storage seems to contribute to the dyslipidemia associated with congenital generalized lipodystrophy syndromes, although the pathophysiological changes may vary with the nature of the mutation involved. Therapeutic management of dyslipidemia in patients with lipodystrophy is primarily based on specific approaches using recombinant leptin therapy. Preclinical studies suggest a potential efficacy of thiazolidinediones that remains to be assessed in dedicated clinical trials. 相似文献
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Fisher NM Meksawan K Limprasertkul A Isackson PJ Pendergast DR Vladutiu GD 《Journal of inherited metabolic disease》2007,30(3):388-399
Summary Cholesterol lowering drugs are associated with myopathic side effects in 7% of those on therapy, which is reversible in most,
but not all patients. This study tested the hypothesis that total body fat oxidation (TBFO) is reduced by statins in patients
with genetic deficiencies in FO, determined by white blood cells (FOwbc) and by molecular analysis of common deficiencies,
and would cause intolerance in some patients. Six patients on statin therapy without myopathic side effects (tolerant) and
7 patients who had previously developed statin-induced myopathic symptoms (intolerant) (age = 58 ± 8.25 yrs, ht. = 169 ± 11 cm,
and wt. = 75.4 ± 14.2 kg) were tested for TBFO (Respiratory Exchange Ratio, RER) pre- and during exercise. FOwbc was not significantly
different between tolerant and intolerant (0.261 ± 0.078 vs. 0.296 ± 0.042 nmol/h per 109 wbc), or normals (0.27 ± 0.09 nmol/h per 109 wbc) and no common molecular abnormalities were found. Pre-exercise RER (0.73 ± 0.05 vs. 0.84 ± 0.05) was significantly lower
in the intolerant group and the Vo
2 at RER = 1.0 (1.27 ± 0.32 vs. 1.87 ± 0.60 L/min) greater than the tolerant. Post-exercise lactates were not different between
groups. Although dietary fat intake was not different, blood lipoprotein levels, particularly triglycerides were 35% lower
in tolerant than previously intolerant. TBFO and blood lipoproteins were reduced in tolerant patients in spite of the absence
of genetic limitations, but not in the intolerant group as hypothesized. Although not conclusive, these data suggest the need
for a prospective study of the effects of statins on fat oxidation.
Competing interests: None declared
References to electronic databases: Carnitine palmitoyltransferase (EC 2.3.1.21) II deficiency, OMIM 255110. Myophosphorylase
(EC 2.4.1.1) deficiency, OMIM 232600. Myoadenylate deaminase (EC 3.5.4.6) deficiency, OMIM 102770. 相似文献
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To evaluate the role of familial and secondary factors in the etiology of severe hypertriglyceridemia, family studies were performed and potential secondary causes of hypertriglyceridemia were evaluated in 54 patients with plasma triglyceride levels above 2000 mg/dl. Every subject had hypertriglyceridemic relatives, compatible with a familial form of hyperlipidemia, although plasma triglyceride levels in the relatives were substantially lower than in the index patients. In 5 index patients, both parents had hyperlipidemia. Four of these 5 had no coexisting secondary cause for hypertriglyceridemia. Forty-six of the remaining 49 (94%) also had potential secondary causes of hypertriglyceridemia, most commonly untreated diabetes mellitus. These findings suggest that severe hypertriglyceridemia frequently results from the coexistence of familial and secondary forms of hyperlipidemia. 相似文献
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S. Zipfel T. Specht W. F. Blum J. Hebebrand P. Englaro M. Hartmann C. Wüster R. Ziegler W. Herzog 《European eating disorders review》1998,6(1):38-47
Plasma levels of leptin correlate with the body mass index and even more with percentage body fat. Determinations of leptin levels might thus offer an alternative to easily assess fat mass in patients with eating disorders. Twenty-five females with the DSM-IV diagnosis of anorexia nervosa (n=12, mean BMI 13·8) and bulimia nervosa (n=13, mean BMI 21·7), respectively, were examined upon referral for inpatient treatment. Methods for the measurement of body fat were BMI and plasma leptin level; dual-energy X-ray absorptiometry (DXA) was used as a reference method. Leptin levels showed a highly significant correlation to body fat measured by DXA (r=0·95, p<0·001). In the group of anorexia patients the correlation of leptin levels with DXA (r=0·91, p<0·001) was significantly higher than with BMI (r=0·62, p<0·05). Measurement of leptin levels in AN patients is a promising approach for determining percentage body fat, especially at admission for inpatient treatment, prior to refeeding. © 1998 John Wiley & Sons, Ltd and Eating Disorders Association. 相似文献
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Mazzuca M Lesage F 《La Revue de médecine interne / fondée ... par la Société nationale francaise de médecine interne》2007,28(8):576-579
INTRODUCTION: K(+) channels allow the passive and selective transport of K(+) ions through the membranes. They control K(+) homeostasis, neuronal and muscular excitabilities, and neurotransmitter and hormone release. EXEGESIS: K(+) channels are composed of pore-forming subunits associated with regulatory subunits. Many different K(+) channels have been identified. CONCLUSION: This diversity is stressed by the growing number of genetic and acquired diseases associated with these channels. 相似文献
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Influence of body fat distribution during childhood on body fat distribution in adulthood: a two-decade follow-up study 总被引:1,自引:0,他引:1
M F Rolland-Cachera F Bellisle M Deheeger F Pequignot M Sempe 《International journal of obesity (2005)》1990,14(6):473-481
Development of body fat distribution was assessed in a two-decade follow-up study. The present article describes the development of various trunk/extremity ratios and gives the figures by age and sex between 1 month to 21 years. The relationship between adult and childhood skinfold (SF) ratio measurements is weak in boys and slightly better in girls. From the present and our previous study, we can select adiposity measurements in children which both are associated to pathologies and have the best correlations with adult values, i.e. the body mass index (BMI) in both sexes, trunk SF in boys and the subscapular/arm SF ratio in girls. Consequently, a boy with both high BMI and trunk SF values or a girl with both high BMI and subscapular/arm SF values have an increased risk of centralized obesity at adult age. 相似文献
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Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder characterized by an intravascular hemolytic anemia. Abnormal blood cells lack a series of glycosylphosphatidylinositol (GPI)-anchored proteins. The lack of GPI-anchored complement regulatory proteins, such as decay-accelerating factor (DAF) and CD59, results in complement-mediated hemolysis and hemoglobinuria. In the affected hematopoietic cells from patients with PNH, the first step in biosynthesis of the GPI anchor is defective. At least four genes are involved in this reaction step, and one of them, an X-linked gene termed PIG-A, is mutated in affected cells. The PIG-A gene is mutated in all patients with PNH reported to date. Here, we review recent advances in the understanding of the molecular pathogenesis of PNH. 相似文献
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Suzuki Y Shimozawa N Imamura A Fukuda S Zhang Z Orii T Kondo N 《Journal of inherited metabolic disease》2001,24(2):151-165
Peroxisome biogenesis disorders (PBDs) are severe autosomal recessive neurological diseases caused by a defect of peroxisomal assembly factors. Zellweger syndrome, the most severe phenotype, is characterized by hypotonia, psychomotor retardation and neuronal migration disorder. Neonatal adrenoleukodystrophy and infantile Refsum disease are milder phenotypes of this disease. Thirteen complementation groups have been established since the genetic heterogeneity of PBDs was elucidated in 1988. Eleven genes for PBDs have been identified either by a functional complementation cloning or by EST homology searches. In 1992, the first gene for PBDs, PEX2, was identified. It encodes peroxisomal integral membrane protein with a RING finger domain. PEX5 and PEX7 are the genes for peroxisomal targeting signal (PTS)-1 and -2 receptors, respectively. PEX3, PEX16 and PEX19 are considered to be required for the early stage of peroxisome biogenesis. PEX13 protein has an SH3 docking site that binds to the PTS-1 receptor. PEX1 and PEX6 encode ABC protein, and PEX10 and PEX12 also encode integral membrane protein, with RING finger. Temperature-sensitivity, whereby peroxisomal biogenesis and metabolic dysfunctions are restored at 30°C in cells from mild phenotypes, is a useful event for predicting the clinical severity and for elucidation of peroxisome biogenesis. Investigations using knockout mice are expected to facilitate understanding of migration disorders. 相似文献
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C Bouchard L Pérusse J Rivest R Roy J Morissette C Allard G Thériault C Leblanc A Tremblay 《International journal of obesity (2005)》1985,9(6):411-422
The association between the genotypes and the alleles at the A, B or C locus of the HLA system and body fat was studied in a total of 1578 individuals subdivided in four cohorts: adult males (n greater than or equal to 204), adult females (n greater than or equal to 184), boys and male adolescents (n greater than or equal to 282), and girls and female adolescents (n greater than or equal to 257). None of these subjects were grossly obese or had known metabolic disorders. Percent body fat from underwater weighing, subcutaneous fat from 6 skinfold measurements, trunk fat (3 skinfolds) and extremity fat (3 skinfolds) were considered in the analysis. Although a few significant associations were encountered, the lack of consistency across samples suggested that they were probably random and biologically not meaningful. The same negative findings were found for the ratio of trunk subcutaneous fat to extremity subcutaneous fat and the ratio of subcutaneous fat (6 skinfolds) to total fat mass. Earlier reports indicating a significant association between high body fat content and antigens B18, Bw35 or Cw4 were not supported by the results of this study. It was concluded that no consistent pattern of association emerged between genotypes or alleles of the HLA system and percent body fat, subcutaneous fat or fat distribution in children and adults of both sexes. 相似文献
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The treatment of hereditary and acquired thrombophilic disorders is based on an understanding of the disease pathophysiology, prevalence, associated morbidity and mortality, and available therapeutic options. Genetic mutations are identified that result in activated protein C (APC) resistance and hyperhomocyst(e)inemia. The underlying etiologies are less well-defined; however, the disorders of factor XII deficiency, dysfibrinogenemia, Wien-Penzing platelet defect, and sticky platelet syndrome (SPS) are treatable inherited thrombophilias. Antithrombin deficiency, protein C and protein S deficiencies, and plasminogen deficiency are disorders both inherited and acquired. Antiphospholipid antibodies, myeloproliferative syndromes, and Trousseau's syndrome are acquired. Treatment for acute arterial thrombosis or venous thromboembolism is the same or similar for all thrombophilic disorders. Long-term management is based on the risk of a primary or recurrent acute thrombotic event, compared with the risk of the proposed therapy. Few blinded, controlled studies are available to validate treatment recommendations. When long-term anticoagulation is advised, careful consideration should be given to the risk associated with therapy. Bleeding risk, variable efficacy, and the risk of cutaneous necrosis limit the use of warfarin. Fixed low-dose unfractionated porcine heparin and low-molecular-weight heparins (LMWH) offer significant advantages for long-term management. These recommendations are derived from an analysis of the pertinent medical literature and are expected to change with the progress of clinical and laboratory investigation. 相似文献