• MeSH
• ateroskleróza etiologie   metabolismus   prevence a kontrola   MeSH
• cholesterol metabolismus   sekrece   MeSH
• hepatocyty enzymologie   metabolismus   MeSH
• interakce mezi receptory a ligandy MeSH
• karcinogeneze * metabolismus   účinky léků   MeSH
• kyselina chenodeoxycholová analýza   metabolismus   sekrece   MeSH
• kyselina cholová analýza   metabolismus   sekrece   MeSH
• lidé MeSH
• metabolické sítě a dráhy MeSH
• metabolismus lipidů * fyziologie   imunologie   MeSH
• neuroprotektivní látky metabolismus   MeSH
• pankreas metabolismus   sekrece   MeSH
• regenerace jater MeSH
• statistika jako téma MeSH
• střevní mikroflóra fyziologie   imunologie   MeSH
• žluč enzymologie   metabolismus   sekrece   MeSH
• žlučové kyseliny a soli * analýza   metabolismus   sekrece   MeSH
• ztučnělá játra MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

OBJECTIVE: Besides their role in lipid absorption, bile acids (BAs) can act as signalling molecules. Cholic acid was shown to counteract obesity and associated metabolic disorders in high-fat-diet (cHF)-fed mice while enhancing energy expenditure through induction of mitochondrial uncoupling protein 1 (UCP1) and activation of non-shivering thermogenesis in brown adipose tissue (BAT). In this study, the effects of another natural BA, chenodeoxycholic acid (CDCA), on dietary obesity, UCP1 in both interscapular BAT and in white adipose tissue (brite cells in WAT), were characterized in dietary-obese mice. RESEARCH DESIGN: To induce obesity and associated metabolic disorders, male 2-month-old C57BL/6J mice were fed cHF (35% lipid wt wt(-1), mainly corn oil) for 4 months. Mice were then fed either (i) for 8 weeks with cHF or with cHF with two different doses (0.5%, 1%; wt wt(-1)) of CDCA (8-week reversion); or (ii) for 3 weeks with cHF or with cHF with 1% CDCA, or pair-fed (PF) to match calorie intake of the CDCA mice fed ad libitum; mice on standard chow diet were also used (3-week reversion). RESULTS: In the 8-week reversion, the CDCA intervention resulted in a dose-dependent reduction of obesity, dyslipidaemia and glucose intolerance, which could be largely explained by a transient decrease in food intake. The 3-week reversion revealed mild CDCA-dependent and food intake-independent induction of UCP1-mediated thermogenesis in interscapular BAT, negligible increase of UCP1 in subcutaneous WAT and a shift from carbohydrate to lipid oxidation. CONCLUSIONS: CDCA could reverse obesity in cHF-fed mice, mainly in response to the reduction in food intake, an effect probably occuring but neglected in previous studies using cholic acid. Nevertheless, CDCA-dependent and food intake-independent induction of UCP1 in BAT (but not in WAT) could contribute to the reduction in adiposity and to the stabilization of the lean phenotype.

• MeSH
• bílá tuková tkáň metabolismus   MeSH
• dieta s vysokým obsahem tuků MeSH
• energetický metabolismus MeSH
• hnědá tuková tkáň metabolismus   MeSH
• iontové kanály metabolismus   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• kyselina chenodeoxycholová metabolismus   MeSH
• metabolismus lipidů MeSH
• mitochondriální proteiny metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši obézní MeSH
• myši MeSH
• obezita metabolismus   MeSH
• oxidační stres MeSH
• porucha glukózové tolerance metabolismus   MeSH
• signální transdukce MeSH
• termogeneze * MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Cholesterol 7?-hydroxylase (CYP7A1), the key regulatory enzyme of bile acid synthesis, displays a pronounced diurnal variation. To better understand the regulation of CYP7A1 activity, three daylong examinations were carried out in 12 healthy men. The concentrations of 7?-hydroxycholest-4-en-3-one (C4), a surrogate marker of CYP7A1 activity, bile acids (BA), insulin, glucose, nonesterified fatty acids, triglycerides, and cholesterol were measured in serum in 90-min intervals from 7 AM till 10 PM. To lower and to increase BA concentration during the study, the subjects received cholestyramine and chenodeoxycholic acid (CDCA), respectively, in two examinations. No drug was used in the control examination. There was a pronounced diurnal variation of C4 concentration with a peak around 1 PM in most of the subjects. The area under the curve (AUC) of C4 concentration was five times higher and three times lower when subjects were treated with cholestyramine and CDCA, respectively. No relationship was found between AUC of C4 and AUC of BA concentration, but AUC of C4 correlated positively with that of insulin. Moreover, short-term treatment with cholestyramine resulted in about 10 % suppression of glycemia throughout the day. Our results suggest that insulin is involved in the regulation of diurnal variation of CYP7A1 activity in humans.

• MeSH
• aktivace enzymů MeSH
• anticholesteremika aplikace a dávkování   MeSH
• cholestenony krev   MeSH
• cholesterol-7-alfa-hydroxylasa metabolismus   MeSH
• cholesterol krev   MeSH
• cholestyraminová pryskyřice aplikace a dávkování   MeSH
• cirkadiánní rytmus fyziologie   MeSH
• dospělí MeSH
• financování organizované MeSH
• gastrointestinální látky aplikace a dávkování   MeSH
• inzulin krev   MeSH
• klinické zkoušky jako téma MeSH
• krevní glukóza metabolismus   MeSH
• kyselina chenodeoxycholová metabolismus   MeSH
• kyseliny mastné neesterifikované krev   MeSH
• lidé MeSH
• referenční hodnoty MeSH
• triglyceridy krev   MeSH
• žlučové kyseliny a soli metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH