Increased plasma total cysteine (tCys) has been associated with obesity and metabolic syndrome in human and some animal studies but the underlying mechanisms remain unclear. In this study, we aimed at evaluating the effects of high cysteine diet administered to SHR-CRP transgenic rats, a model of metabolic syndrome and inflammation. SHR-CRP rats were fed either standard (3.2 g cystine/kg diet) or high cysteine diet (HCD, enriched with additional 4 g L-cysteine/kg diet). After 4 weeks, urine, plasma and tissue samples were collected and parameters of metabolic syndrome, sulfur metabolites and hepatic gene expression were evaluated. Rats on HCD exhibited similar body weights and weights of fat depots, reduced levels of serum insulin, and reduced oxidative stress in the liver. The HCD did not change concentrations of tCys in tissues and body fluids while taurine in tissues and body fluids, and urinary sulfate were significantly increased. In contrast, betaine levels were significantly reduced possibly compensating for taurine elevation. In summary, increased Cys intake did not induce obesity while it ameliorated insulin resistance in the SHR-CRP rats, possibly due to beneficial effects of accumulating taurine.
Hepcidin deficiency leads to iron overload by increased dietary iron uptake and iron release from storage cells. The most frequent mutation in Hfe leads to reduced hepcidin expression and thereby causes iron overload. Recent findings suggested that HFE activates hepcidin expression predominantly via the BMP type I receptor ALK3. Here, we investigated whether HFE exclusively utilizes ALK3 or other signaling mechanisms also. We generated mice with double deficiency of Hfe and hepatocyte-specific Alk3 and compared the iron overload phenotypes of these double knockout mice to single hepatocyte-specific Alk3 deficient or Hfe knockout mice. Double Hfe-/-/hepatic Alk3fl/fl;Alb-Cre knockouts develop a similar iron overload phenotype compared to single hepatocyte-specific Alk3 deficient mice hallmarked by serum iron levels, tissue iron content and hepcidin levels of similar grades. HFE protein levels were increased in Alk3fl/fl;Alb-Cre mice compared to Alk3fl/fl mice, which was caused by iron overload - and not by Alk3 deficiency. The data provide evidence by genetic means that 1. HFE exclusively uses the BMP type I receptor ALK3 to induce hepcidin expression and 2. HFE protein expression is induced by iron overload, which further emphasizes the iron sensing function of HFE.
- MeSH
- hepcidiny * genetika MeSH
- histokompatibilita - antigeny třídy I genetika MeSH
- játra metabolismus MeSH
- myši knockoutované MeSH
- myši MeSH
- přetížení železem * genetika MeSH
- protein hemochromatózy genetika MeSH
- receptory morfogenetických kostních proteinů typu I MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Hereditary xanthinuria (type I) is caused by an inherited deficiency of the xanthine oxidorectase (XDH/XO), and is characterized by very low concentration of uric acid in blood and urine and high concentration of urinary xanthine, leading to urolithiasis. Type II results from a combined deficiency of XDH/XO and aldehyde oxidase. Patients present with hematuria, renal colic, urolithiasis or even acute renal failure. Clinical symptoms are the same for both types. In a third type, clinically distinct, sulfite oxidase activity is missing as well as XDH/XO and aldehyde oxidase. The prevalence is not known, but about 150 cases have been described so far. Hypouricemia is sometimes overlooked, that´s why we have set up the diagnostic flowchart. This consists of a) evaluation of uric acid concentrations in serum and urine with exclusion of primary renal hypouricemia, b) estimation of urinary xanthine, c) allopurinol loading test, which enables to distinguish type I and II; and finally assay of xanthine oxidoreductase activity in plasma with molecular genetic analysis. Following this diagnostic procedure we were able to find first patients with hereditary xanthinuria in our Czech population. We have detected nine cases, which is one of the largest group worldwide. Four patients were asymptomatic. All had profound hypouricemia, which was the first sign and led to referral to our department. Urinary concentrations of xanthine were in the range of 170-598 mmol/mol creatinine (normal < 30 mmol/mol creatinine). Hereditary xanthinuria is still unrecognized disorder and subjects with unexplained hypouricemia need detailed purine metabolic investigation.
- MeSH
- aldehydoxidasa krev nedostatek moč MeSH
- alopurinol metabolismus MeSH
- diferenciální diagnóza MeSH
- dítě MeSH
- dospělí MeSH
- kyselina močová krev moč MeSH
- lidé MeSH
- močové kameny krev epidemiologie moč MeSH
- poruchy metabolismu purinů a pyrimidinů krev diagnóza epidemiologie moč MeSH
- předškolní dítě MeSH
- puriny metabolismus MeSH
- vrozené poruchy metabolismu krev diagnóza epidemiologie moč MeSH
- vrozené poruchy tubulárního transportu krev epidemiologie moč MeSH
- xanthin krev moč MeSH
- xanthindehydrogenasa krev nedostatek metabolismus moč MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- alely * MeSH
- galaktosemie genetika MeSH
- lidé MeSH
- molekulární sekvence - údaje MeSH
- mutační analýza DNA MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza DNA MeSH
- sekvenční delece MeSH
- UDP-galaktosapyrofosforylasa genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
