Circulating vaspin is unrelated to insulin sensitivity in a cohort of nondiabetic humans

Objective: To study the association of vaspin with glucose metabolism. Design: Cross-sectional and intervention study. Subjects and methods: The association of serum vaspin with metabolic and anthropometric characteristics was investigated in 108 volunteers. Euglycemic–hyperinsulinemic clamps (EHC) were performed in 83 of the participants. Changes of circulating vaspin levels were additionally studied in a crossover study using 300 min EHC with lipid versus saline infusion (n=10). Results: Neither glucose tolerance status nor insulin sensitivity, both as measured using EHCs and using homeostasis model assessment for insulin resistance (HOMA-IR), was significantly associated with serum vaspin in the cross-sectional study. Furthermore, there was no effect of short-term lipid-induced insulin resistance due to a 300 min intravenous lipid challenge on circulating vaspin. However, circulating vaspin levels were significantly elevated in women using oral contraceptives (OC), both compared to women without OC intake (1.17±0.26 vs 0.52±0.09 ng/ml, P=0.02) and males (1.17±0.26 vs 0.29±0.04 ng/ml, P=0.01). After exclusion of OC using females and stratification according to body mass index (BMI), a significant sexual dimorphism in subjects with a BMI <25 kg/m2 was observed (males 0.21±0.04 ng/ml versus females 0.70±0.16 ng/ml, P=0.009). Conclusion: Our results support the existence of a sexual dimorphism regarding circulating vaspin. The lack of an association of serum vaspin with HOMA-IR and M value indicates, however, no major role for vaspin concerning insulin sensitivity in nondiabetic humans

Free fatty acids link metabolism and regulation of the insulin-sensitizing fibroblast growth factor-21

OBJECTIVE—Fibroblast growth factor (FGF)-21 improves insulin sensitivity and lipid metabolism in obese or diabetic animal models, while human studies revealed increased FGF-21 levels in obesity and type 2 diabetes. Given that FGF-21 has been suggested to be a peroxisome proliferator–activator receptor (PPAR) –dependent regulator of fasting metabolism, we hypothesized that free fatty acids (FFAs), natural agonists of PPAR, might modify FGF-21 levels. RESEARCH DESIGN AND METHODS—The effect of fatty acids on FGF-21 was investigated in vitro in HepG2 cells. Within a randomized controlled trial, the effects of elevated FFAs were studied in 21 healthy subjects (13 women and 8 men). Within a clinical trial including 17 individuals, the effect of insulin was analyzed using an hyperinsulinemic-euglycemic clamp and the effect of PPAR activation was studied subsequently in a rosiglitazone treatment trial over 8 weeks. RESULTS—Oleate and linoleate increased FGF-21 expression and secretion in a PPAR-dependent fashion, as demonstrated by small-interfering RNA–induced PPAR knockdown, while palmitate had no effect. In vivo, lipid infusion induced an increase of circulating FGF-21 in humans, and a strong correlation between the change in FGF-21 levels and the change in FFAs was observed. An artificial hyperinsulinemia, which was induced to delineate the potential interaction between elevated FFAs and hyperinsulinemia, revealed that hyperinsulinemia also increased FGF-21 levels in vivo, while rosiglitazone treatment had no effect. CONCLUSIONS—The results presented here offer a mechanism explaining the induction of the metabolic regulator FGF-21 in the fasting situation but also in type 2 diabetes and obesity

Extending the spectrum of Ellis van Creveld syndrome: a large family with a mild mutation in the EVC gene

<p>Abstract</p> <p>Background</p> <p>Ellis-van Creveld (EvC) syndrome is characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails and teeth and is inherited in an autosomal recessive pattern. We report a family with complex septal cardiac defects, rhizomelic limb shortening, and polydactyly, without the typical lip, dental, and nail abnormalities of EvC. The phenotype was inherited in an autosomal recessive pattern, with one instance of pseudodominant inheritance.</p> <p>Methods</p> <p>Because of the phenotypic overlap with EvC, microsatellite markers were used to test for linkage to the <it>EVC/EVC2 </it>locus. The results did not exclude linkage, so samples were sequenced for mutations.</p> <p>Results</p> <p>We identified a c.1868T>C mutation in <it>EVC</it>, which predicts p.L623P, and was homozygous in affected individuals.</p> <p>Conclusion</p> <p>We conclude that this <it>EVC </it>mutation is hypomorphic and that such mutations can cause a phenotype of cardiac and limb defects that is less severe than typical EvC. <it>EVC </it>mutation analysis should be considered in patients with cardiac and limb malformations, even if they do not manifest typical EvC syndrome.</p

Extending the spectrum of Ellis van Creveld syndrome: a large family with a mild mutation in the EVC gene

<p>Abstract</p> <p>Background</p> <p>Ellis-van Creveld (EvC) syndrome is characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails and teeth and is inherited in an autosomal recessive pattern. We report a family with complex septal cardiac defects, rhizomelic limb shortening, and polydactyly, without the typical lip, dental, and nail abnormalities of EvC. The phenotype was inherited in an autosomal recessive pattern, with one instance of pseudodominant inheritance.</p> <p>Methods</p> <p>Because of the phenotypic overlap with EvC, microsatellite markers were used to test for linkage to the <it>EVC/EVC2 </it>locus. The results did not exclude linkage, so samples were sequenced for mutations.</p> <p>Results</p> <p>We identified a c.1868T>C mutation in <it>EVC</it>, which predicts p.L623P, and was homozygous in affected individuals.</p> <p>Conclusion</p> <p>We conclude that this <it>EVC </it>mutation is hypomorphic and that such mutations can cause a phenotype of cardiac and limb defects that is less severe than typical EvC. <it>EVC </it>mutation analysis should be considered in patients with cardiac and limb malformations, even if they do not manifest typical EvC syndrome.</p

Impact of metabolic stress induced by diets, aging and fasting on tissue oxygen consumption

OBJECTIVE: Alterations in mitochondrial function play an important role in the development of various diseases, such as obesity, insulin resistance, steatohepatitis, atherosclerosis and cancer. However, accurate assessment of mitochondrial respiration ex vivo is limited and remains highly challenging. Using our novel method, we measured mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) of metabolically relevant tissues ex vivo to investigate the impact of different metabolic stressors on mitochondrial function. METHODS: Comparative analysis of OCR and ECAR in young mice fed either 12 weeks high-fat (HFD), high-sucrose (HSD), or western diet (WD), a HFD in matured mice, 2 years prolonged aging on standard-control diet (STD), as well as fasting in tissue biopsies. RESULTS: While diets had only marginal effects on mitochondrial respiration, respiratory chain complexes II and IV were reduced. Moreover, matured HFD-fed mice showed a decreased hepatic metabolic flexibility and prolonged aging increased OCR in brown adipose tissue. Interestingly, fasting boosted pancreatic and hepatic OCR while decreasing weight of those organs. Furthermore, ECAR measurements in adipose tissue could indicate its lipolytic capacity. CONCLUSION: Using ex vivo tissue measurements, we could extensively analyze mitochondrial function of liver, adipose tissue, pancreas and heart revealing effects of metabolic stress, especially aging

The Discovery Potential of a Super B Factory

The Proceedings of the 2003 SLAC Workshops on flavor physics with a high luminosity asymmetric e+e- collider. The sensitivity of flavor physics to physics beyond the Standard Model is addressed in detail, in the context of the improvement of experimental measurements and theoretical calculations.Comment: 476 pages. Printed copies may be obtained by request to [email protected] . arXiv admin note: v2 appears to be identical to v