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Tatu A Miettinen - One of the best experts on this subject based on the ideXlab platform.

  • prognostic significance of serum cholesterol Lathosterol and sitosterol in old age a 17 year population study
    Annals of Medicine, 2011
    Co-Authors: Reijo S Tilvis, Jaakko Valvanne, Timo E Strandberg, Tatu A Miettinen
    Abstract:

    AbstractBackground. Low serum total cholesterol is frequently associated with worse survival in older people, but mechanisms of this association are poorly understood.Aims. Characteristics of cholesterol metabolism were related to survival in a random 75 + population sample.Methods. Serum cholesterol and Lathosterol, and sitosterol were measured in random persons (n = 623) of birth cohorts (1904, 1909, and 1914) in 1990, and all persons were followed for 17 years.Results. Total cholesterol declined in old age, and low cholesterol was associated with poor health and multi-morbidity. Cholesterol below 5.0 mmol/L was associated with accelerated all-cause mortality (age- and gender-adjusted hazard ratio (HR) 1.54; 95% CI 1.21–1.97; P < 0.001) and vascular mortality (HR 2.13 (1.42–3.07); P < 0.001). Lathosterol (indicating cholesterol synthesis) and sitosterol (indicating cholesterol absorption) also decreased with deteriorating health. Low Lathosterol, sitosterol, and cholesterol predicted mortality additivel...

  • serum cholestanol cholesterol precursors and plant sterols in different inflammatory bowel diseases
    Digestion, 1996
    Co-Authors: Kalle Hakala, M Vuoristo, Tatu A Miettinen
    Abstract:

    The role of cholestasis and ileal dysfunction on sterol metabolism was studied in 79 patients with inflammatory bowel diseases (IBDs) and in 23 irritable bowel syndrome (IBS) controls by determining serum sterol/cholesterol proportions. The sterols included cholesterol precursors (Δ8-cholestenol, desmo-sterol and Lathosterol), markers of cholesterol synthesis, cholestanol and plant sterols (campesterol and sitosterol), markers of cholesterol absorption and biliary secretion. The IBD patients were subgrouped into distal ulcerative colitis (dUC, n = 21), pancolitis (pUC, n = 29), ileal Crohn’s disease (iCD, n = 20) and colonic Crohn’s disease (cCD, n = 9). The cholestanol proportions were increased in the 3 colonic IBD groups, up to two times in cCD patients and seven times in a case with clinically overt primary sclerosing cholangitis, but were within the control IBS levels in the patients with iCD. The sitosterol, but not campesterol, proportion was significantly increased only in the pUC group. In the iCD group only the serum precursor sterol proportions, especially those for Δ8-cholestenol and Lathosterol, were elevated probably due to ileal dysfunction induced bile acid malabsorption and compensatorily increased cholesterol synthesis. In conclusion, the findings suggest that the increased cholestanol proportion in colonic IBD is determined mainly by impaired biliary elimination of this sterol, while in ileal affision the dominating change in sterol balance is activated cholesterol synthesis. Thus increased serum cholestanol is a novel finding in colonic IBD, apparently indicating the presence of subclinical cholestasis in a marked number (20-50%) of IBD patients.

  • noncholesterol sterols in bile and stones of patients with cholesterol and pigment stones
    Hepatology, 1996
    Co-Authors: T E Miettinen, Y.antero Kesäniemi, Heikki Järvinen, Helena Gylling, E Silvennoinen, Tatu A Miettinen
    Abstract:

    Human bile and cholesterol gallstones contain sterols including methylated (lanosterol and other dimethyl and monomethyl sterols), and demethylated cholesterol precursor sterols (Δ 8-Lathosterol, Lathosterol, and desmosterol), plant sterols (campesterol and sitosterol), and cholestanol. The aim of the study was to analyze the noncholesterol sterols in gallbladder bile and stones from female and male patients with cholesterol stones (CS) and pigment stones (PS) to ascertain whether any sterol fraction contributes to the gallstone formation. Classification of gallstones to CS and PS was performed on the basis of the stone cholesterol content. The study group consisted of 165 consecutive cholecystectomized patients, 150 with CS and 15 with PS. Bile acids and sterols were quantitated using gas-liquid chromatography (GLC). The biliary lipid and noncholesterol sterol/cholesterol proportions were similar in the CS and PS patients. The proportions of methylated and plant sterols were significantly lower in the CS than in bile, whereas those of Δ 8-Lathosterol, Lathosterol, and cholestanol were significantly higher. The PS, in contrast to the CS, were neither sex nor weight related. The bile acid and phospholipid concentrations and the proportions of lanosterol, Δ 8, 24-dimethylsterol, and sitosterol were up to 50 times higher and those of Δ 8-Lathosterol and Lathosterol twice lower in the PS than in the CS. The results suggest that, in general, the stones with low cholesterol content are proportionately richer in nonpolar precursor and plant sterols and lower in demethylated precursors, the situation being opposite for the CS. The stone/bile ratios suggest that in both stone groups, but especially in the CS, levels of the polar precursor sterols and cholestanol were enriched in the stone, whereas levels of the nonpolar precursor sterols, and to a lesser extent plant sterols, were not enriched in the stone despite their high biliary proportions.

  • liver transplantation modifies serum cholestanol cholesterol precursor and plant sterol levels
    Clinica Chimica Acta, 1992
    Co-Authors: Katriina Nikkilä, Krister Höckerstedt, Tatu A Miettinen
    Abstract:

    Proportions of cholesterol precursors (squalene, Δ8-cholestenol, desmosterol and Lathosterol), plant sterols (campesterol and sitosterol) and cholestanol to cholesterol in serum were measured before and serially after liver transplantation in eight patients with primary biliary cirrhosis (PBC) and three with acute liver necrosis. The preoperative proportions of cholestanol were 12 and 3-times higher in the PBC and necrosis groups, respectively, than in a control group of 27 individuals, while those of Lathosterol were low in both groups and the campesterol/sitosterol ratio in the PBC group. During the operation the proportions of cholestanol fell sharply and those of Lathosterol rose especially in the PBC group. During the postoperative follow-up of 5 weeks the proportions of the non-cholesterol sterols were markedly improved especially in the necrosis group yet those of cholestanol remained high and the campesterol/sitosterol ratios low, particularly in the PBC group. The proportions of Lathosterol increased gradually almost to the control limits within the postoperative 5-week period, whereas those of desmosterol decreased. The non-cholesterol sterol values were not related to acute rejections, while significant correlations of cholestanol to liver function tests was found especially at the end of the follow-up.

  • serum and hepatic cholestanol squalene and noncholesterol sterols in man a study on liver transplantation
    Hepatology, 1992
    Co-Authors: Katriina Nikkilä, Krister Höckerstedt, Tatu A Miettinen
    Abstract:

    Serum noncholesterol sterols indicate overall cholesterol metabolism in a variety of experimental and clinical conditions. In patients with advanced primary biliary cirrhosis serum cholestanol, a 5a-derivative of cholesterol, is markedly increased, and cholesterol precursors, which are indicators of cholesterol synthesis, are clearly reduced, as is the ratio of plant sterols (campesterol/sitosterol). Therefore these variables were studied in the livers and sera of 23 patients undergoing liver transplantation (16 patients with chronic liver disease, 4 with acute liver failure and 3 receiving second liver) and in 10 healthy controls. A most striking finding was the markedly high liver and serum levels of cholestanol in patients with chronic end-stage liver disease, a finding specific for cholestanol but not for other sterols. Of the cholesterol precursor sterols, Lathosterol exhibited low contents in both the serum and liver of the cirrhotic patient group, supposedly reflecting decreased cholesterol synthesis. In contrast to the largely similar levels of noncholesterol sterols in serum and liver and the positive correlations between the two sources, the serum squalene levels were markedly lower than the hepatic levels, with a negative correlation between the serum and the liver, suggesting that serum squalene content poorly reflects cholesterol synthesis. In contrast to campesterol, serum and liver sitosterol tended to show increases, and the serum and hepatic campesterol/sitosterol ratios were lower in the chronic liver disease patients than in the controls, probably because of the more consistently impaired biliary elimination of sitosterol in those patients. The findings show that cholestanol is markedly increased and that Lathosterol and the campesterol/sitosterol ratio are decreased in both the serum and the liver of patients with chronic end-stage liver disease. Unlike squalene, serum noncholesterol sterols are quite evenly distributed with the respective hepatic sterols. Gas-liquid chromatographic quantitation of these sterols from nonsaponifiable serum lipids may offer a new means of determining the actual end stages of chronic liver diseases. (HEPATOLOGY 1992;15:863–870).

Giuseppe Castaldo - One of the best experts on this subject based on the ideXlab platform.

  • lumacaftor ivacaftor improves liver cholesterol metabolism but does not influence hypocholesterolemia in patients with cystic fibrosis
    Journal of Cystic Fibrosis, 2020
    Co-Authors: Monica Gelzo, Paola Iacotucci, Mafalda Caputo, Gustavo Cernera, Marika Comegna, Vincenzo Carnovale, Gaetano Corso, Giuseppe Castaldo
    Abstract:

    Abstract Background Cystic fibrosis (CF) patients have reduced intestinal absorption of sterols and, despite enhanced endogenous synthesis, low plasma cholesterol. Lumacaftor/ivacaftor CFTR protein modulator therapy is used to improve the clinical outcome of CF patients homozygous for F508del mutation (homo-deltaF508). Aim of the study is to evaluate the cholesterol metabolism and hepatobiliary injury/function in adult homo-deltaF508 patients, before and after lumacaftor/ivacaftor treatment. Baseline parameters in homo-deltaF508 patients were compared to those in CF patients compound heterozygous for F508del mutation and another severe mutation (hetero-deltaF508). Methods Cholesterol metabolism was evaluated measuring plasma phytosterols and cholestanol, as intestinal absorption markers, and Lathosterol, as liver biosynthesis marker. We quantified serum vitamin E, as nutritional marker. We evaluated liver injury by aspartate aminotransferase (AST) and alanine transaminase (ALT), biliary injury by γ-glutamyltransferase (γGT) and AP, and the liver function by bilirubin and albumin. Results Before the treatment, homo-deltaF508 patients (n = 20) had significantly lower cholesterol and vitamin E compared to hetero-deltaF508 (n = 20). Lumacaftor/ivacaftor treatment caused: 1) further reduction of cholesterol; 2) Lathosterol reduction, suggesting a normalization of endogenous synthesis; 3) cholestanol and vitamin E increment, indicating an improvement of lipid digestion/absorption. Vitamin E difference (after-before treatment) was positively associated to treatment months. Alkaline phosphatase was also reduced. Conclusions These data suggest an effect of lumacaftor/ivacaftor on cholesterol metabolism and enterohepatic flux in CF patients. However, lumacaftor/ivacaftor does not promote the increase of cholesterol serum concentration that on the contrary declines. Further studies are needed to research the real mechanism causing this reduction.

  • Lumacaftor/ivacaftor improves liver cholesterol metabolism but does not influence hypocholesterolemia in patients with cystic fibrosis.
    Journal of Cystic Fibrosis, 2020
    Co-Authors: Monica Gelzo, Paola Iacotucci, Mafalda Caputo, Gustavo Cernera, Marika Comegna, Vincenzo Carnovale, Gaetano Corso, Giuseppe Castaldo
    Abstract:

    Abstract Background Cystic fibrosis (CF) patients have reduced intestinal absorption of sterols and, despite enhanced endogenous synthesis, low plasma cholesterol. Lumacaftor/ivacaftor CFTR protein modulator therapy is used to improve the clinical outcome of CF patients homozygous for F508del mutation (homo-deltaF508). Aim of the study is to evaluate the cholesterol metabolism and hepatobiliary injury/function in adult homo-deltaF508 patients, before and after lumacaftor/ivacaftor treatment. Baseline parameters in homo-deltaF508 patients were compared to those in CF patients compound heterozygous for F508del mutation and another severe mutation (hetero-deltaF508). Methods Cholesterol metabolism was evaluated measuring plasma phytosterols and cholestanol, as intestinal absorption markers, and Lathosterol, as liver biosynthesis marker. We quantified serum vitamin E, as nutritional marker. We evaluated liver injury by aspartate aminotransferase (AST) and alanine transaminase (ALT), biliary injury by γ-glutamyltransferase (γGT) and AP, and the liver function by bilirubin and albumin. Results Before the treatment, homo-deltaF508 patients (n = 20) had significantly lower cholesterol and vitamin E compared to hetero-deltaF508 (n = 20). Lumacaftor/ivacaftor treatment caused: 1) further reduction of cholesterol; 2) Lathosterol reduction, suggesting a normalization of endogenous synthesis; 3) cholestanol and vitamin E increment, indicating an improvement of lipid digestion/absorption. Vitamin E difference (after-before treatment) was positively associated to treatment months. Alkaline phosphatase was also reduced. Conclusions These data suggest an effect of lumacaftor/ivacaftor on cholesterol metabolism and enterohepatic flux in CF patients. However, lumacaftor/ivacaftor does not promote the increase of cholesterol serum concentration that on the contrary declines. Further studies are needed to research the real mechanism causing this reduction.

Monica Gelzo - One of the best experts on this subject based on the ideXlab platform.

  • lumacaftor ivacaftor improves liver cholesterol metabolism but does not influence hypocholesterolemia in patients with cystic fibrosis
    Journal of Cystic Fibrosis, 2020
    Co-Authors: Monica Gelzo, Paola Iacotucci, Mafalda Caputo, Gustavo Cernera, Marika Comegna, Vincenzo Carnovale, Gaetano Corso, Giuseppe Castaldo
    Abstract:

    Abstract Background Cystic fibrosis (CF) patients have reduced intestinal absorption of sterols and, despite enhanced endogenous synthesis, low plasma cholesterol. Lumacaftor/ivacaftor CFTR protein modulator therapy is used to improve the clinical outcome of CF patients homozygous for F508del mutation (homo-deltaF508). Aim of the study is to evaluate the cholesterol metabolism and hepatobiliary injury/function in adult homo-deltaF508 patients, before and after lumacaftor/ivacaftor treatment. Baseline parameters in homo-deltaF508 patients were compared to those in CF patients compound heterozygous for F508del mutation and another severe mutation (hetero-deltaF508). Methods Cholesterol metabolism was evaluated measuring plasma phytosterols and cholestanol, as intestinal absorption markers, and Lathosterol, as liver biosynthesis marker. We quantified serum vitamin E, as nutritional marker. We evaluated liver injury by aspartate aminotransferase (AST) and alanine transaminase (ALT), biliary injury by γ-glutamyltransferase (γGT) and AP, and the liver function by bilirubin and albumin. Results Before the treatment, homo-deltaF508 patients (n = 20) had significantly lower cholesterol and vitamin E compared to hetero-deltaF508 (n = 20). Lumacaftor/ivacaftor treatment caused: 1) further reduction of cholesterol; 2) Lathosterol reduction, suggesting a normalization of endogenous synthesis; 3) cholestanol and vitamin E increment, indicating an improvement of lipid digestion/absorption. Vitamin E difference (after-before treatment) was positively associated to treatment months. Alkaline phosphatase was also reduced. Conclusions These data suggest an effect of lumacaftor/ivacaftor on cholesterol metabolism and enterohepatic flux in CF patients. However, lumacaftor/ivacaftor does not promote the increase of cholesterol serum concentration that on the contrary declines. Further studies are needed to research the real mechanism causing this reduction.

  • Lumacaftor/ivacaftor improves liver cholesterol metabolism but does not influence hypocholesterolemia in patients with cystic fibrosis.
    Journal of Cystic Fibrosis, 2020
    Co-Authors: Monica Gelzo, Paola Iacotucci, Mafalda Caputo, Gustavo Cernera, Marika Comegna, Vincenzo Carnovale, Gaetano Corso, Giuseppe Castaldo
    Abstract:

    Abstract Background Cystic fibrosis (CF) patients have reduced intestinal absorption of sterols and, despite enhanced endogenous synthesis, low plasma cholesterol. Lumacaftor/ivacaftor CFTR protein modulator therapy is used to improve the clinical outcome of CF patients homozygous for F508del mutation (homo-deltaF508). Aim of the study is to evaluate the cholesterol metabolism and hepatobiliary injury/function in adult homo-deltaF508 patients, before and after lumacaftor/ivacaftor treatment. Baseline parameters in homo-deltaF508 patients were compared to those in CF patients compound heterozygous for F508del mutation and another severe mutation (hetero-deltaF508). Methods Cholesterol metabolism was evaluated measuring plasma phytosterols and cholestanol, as intestinal absorption markers, and Lathosterol, as liver biosynthesis marker. We quantified serum vitamin E, as nutritional marker. We evaluated liver injury by aspartate aminotransferase (AST) and alanine transaminase (ALT), biliary injury by γ-glutamyltransferase (γGT) and AP, and the liver function by bilirubin and albumin. Results Before the treatment, homo-deltaF508 patients (n = 20) had significantly lower cholesterol and vitamin E compared to hetero-deltaF508 (n = 20). Lumacaftor/ivacaftor treatment caused: 1) further reduction of cholesterol; 2) Lathosterol reduction, suggesting a normalization of endogenous synthesis; 3) cholestanol and vitamin E increment, indicating an improvement of lipid digestion/absorption. Vitamin E difference (after-before treatment) was positively associated to treatment months. Alkaline phosphatase was also reduced. Conclusions These data suggest an effect of lumacaftor/ivacaftor on cholesterol metabolism and enterohepatic flux in CF patients. However, lumacaftor/ivacaftor does not promote the increase of cholesterol serum concentration that on the contrary declines. Further studies are needed to research the real mechanism causing this reduction.

  • age related changes of cholestanol and Lathosterol plasma concentrations an explorative study
    Lipids in Health and Disease, 2019
    Co-Authors: Monica Gelzo, Gaetano Corso, Maria Donata Di Taranto, Concetta Sica, Antonio Boscia, Francesco Papagni, Giuliana Fortunato, Antonio Dello Russo
    Abstract:

    Cerebrotendinous xanthomatosis (CTX) and Lathosterolosis represent two treatable inherited disorders of cholesterol metabolism that are characterized by the accumulation of cholestanol and Lathosterol, respectively. The age of the patients suspected of having these disorders is highly variable due to the very different phenotypes. The early diagnosis of these disorders is important because specific therapeutic treatment could prevent the disease progression. The biochemical diagnosis of these defects is generally performed analyzing the sterol profile. Since age-related levels of these sterols are lacking, this study aims to determine a preliminary comparison of plasma levels of cholestanol and Lathosterol among Italian unaffected newborns, children and healthy adults. The sterols were extracted from 130 plasma samples (24 newborns, 33 children and 73 adults) by a liquid-liquid separation method and quantified by gas chromatography coupled with a flame ionization detector. Cholesterol, cholestanol and Lathosterol levels together with the cholestanol/cholesterol and Lathosterol/cholesterol ratios are statistically different among the three groups. Cholesterol levels progressively increased from newborns to children and to adults, whereas cholestanol/cholesterol and cholestanol/Lathosterol ratios progressively decreased from newborns to children and to adults. Lathosterol levels were higher in adults than in both newborns and children. In the total population a positive correlation was observed between cholesterol levels and both cholestanol (correlation coefficient = 0.290, p = 0.001) and Lathosterol levels (correlation coefficient = 0.353, p <  0.0001). Although this study can only be considered an explorative experience due to the low number of analyzed samples, we revealed several differences of plasma cholestanol and Lathosterol levels and their ratios to cholesterol levels among newborns, children and adults. These evidences indicate the need of age-related reference values of cholestanol and Lathosterol concentrations, including also newborns and children.

Gaetano Corso - One of the best experts on this subject based on the ideXlab platform.

  • lumacaftor ivacaftor improves liver cholesterol metabolism but does not influence hypocholesterolemia in patients with cystic fibrosis
    Journal of Cystic Fibrosis, 2020
    Co-Authors: Monica Gelzo, Paola Iacotucci, Mafalda Caputo, Gustavo Cernera, Marika Comegna, Vincenzo Carnovale, Gaetano Corso, Giuseppe Castaldo
    Abstract:

    Abstract Background Cystic fibrosis (CF) patients have reduced intestinal absorption of sterols and, despite enhanced endogenous synthesis, low plasma cholesterol. Lumacaftor/ivacaftor CFTR protein modulator therapy is used to improve the clinical outcome of CF patients homozygous for F508del mutation (homo-deltaF508). Aim of the study is to evaluate the cholesterol metabolism and hepatobiliary injury/function in adult homo-deltaF508 patients, before and after lumacaftor/ivacaftor treatment. Baseline parameters in homo-deltaF508 patients were compared to those in CF patients compound heterozygous for F508del mutation and another severe mutation (hetero-deltaF508). Methods Cholesterol metabolism was evaluated measuring plasma phytosterols and cholestanol, as intestinal absorption markers, and Lathosterol, as liver biosynthesis marker. We quantified serum vitamin E, as nutritional marker. We evaluated liver injury by aspartate aminotransferase (AST) and alanine transaminase (ALT), biliary injury by γ-glutamyltransferase (γGT) and AP, and the liver function by bilirubin and albumin. Results Before the treatment, homo-deltaF508 patients (n = 20) had significantly lower cholesterol and vitamin E compared to hetero-deltaF508 (n = 20). Lumacaftor/ivacaftor treatment caused: 1) further reduction of cholesterol; 2) Lathosterol reduction, suggesting a normalization of endogenous synthesis; 3) cholestanol and vitamin E increment, indicating an improvement of lipid digestion/absorption. Vitamin E difference (after-before treatment) was positively associated to treatment months. Alkaline phosphatase was also reduced. Conclusions These data suggest an effect of lumacaftor/ivacaftor on cholesterol metabolism and enterohepatic flux in CF patients. However, lumacaftor/ivacaftor does not promote the increase of cholesterol serum concentration that on the contrary declines. Further studies are needed to research the real mechanism causing this reduction.

  • Lumacaftor/ivacaftor improves liver cholesterol metabolism but does not influence hypocholesterolemia in patients with cystic fibrosis.
    Journal of Cystic Fibrosis, 2020
    Co-Authors: Monica Gelzo, Paola Iacotucci, Mafalda Caputo, Gustavo Cernera, Marika Comegna, Vincenzo Carnovale, Gaetano Corso, Giuseppe Castaldo
    Abstract:

    Abstract Background Cystic fibrosis (CF) patients have reduced intestinal absorption of sterols and, despite enhanced endogenous synthesis, low plasma cholesterol. Lumacaftor/ivacaftor CFTR protein modulator therapy is used to improve the clinical outcome of CF patients homozygous for F508del mutation (homo-deltaF508). Aim of the study is to evaluate the cholesterol metabolism and hepatobiliary injury/function in adult homo-deltaF508 patients, before and after lumacaftor/ivacaftor treatment. Baseline parameters in homo-deltaF508 patients were compared to those in CF patients compound heterozygous for F508del mutation and another severe mutation (hetero-deltaF508). Methods Cholesterol metabolism was evaluated measuring plasma phytosterols and cholestanol, as intestinal absorption markers, and Lathosterol, as liver biosynthesis marker. We quantified serum vitamin E, as nutritional marker. We evaluated liver injury by aspartate aminotransferase (AST) and alanine transaminase (ALT), biliary injury by γ-glutamyltransferase (γGT) and AP, and the liver function by bilirubin and albumin. Results Before the treatment, homo-deltaF508 patients (n = 20) had significantly lower cholesterol and vitamin E compared to hetero-deltaF508 (n = 20). Lumacaftor/ivacaftor treatment caused: 1) further reduction of cholesterol; 2) Lathosterol reduction, suggesting a normalization of endogenous synthesis; 3) cholestanol and vitamin E increment, indicating an improvement of lipid digestion/absorption. Vitamin E difference (after-before treatment) was positively associated to treatment months. Alkaline phosphatase was also reduced. Conclusions These data suggest an effect of lumacaftor/ivacaftor on cholesterol metabolism and enterohepatic flux in CF patients. However, lumacaftor/ivacaftor does not promote the increase of cholesterol serum concentration that on the contrary declines. Further studies are needed to research the real mechanism causing this reduction.

  • age related changes of cholestanol and Lathosterol plasma concentrations an explorative study
    Lipids in Health and Disease, 2019
    Co-Authors: Monica Gelzo, Gaetano Corso, Maria Donata Di Taranto, Concetta Sica, Antonio Boscia, Francesco Papagni, Giuliana Fortunato, Antonio Dello Russo
    Abstract:

    Cerebrotendinous xanthomatosis (CTX) and Lathosterolosis represent two treatable inherited disorders of cholesterol metabolism that are characterized by the accumulation of cholestanol and Lathosterol, respectively. The age of the patients suspected of having these disorders is highly variable due to the very different phenotypes. The early diagnosis of these disorders is important because specific therapeutic treatment could prevent the disease progression. The biochemical diagnosis of these defects is generally performed analyzing the sterol profile. Since age-related levels of these sterols are lacking, this study aims to determine a preliminary comparison of plasma levels of cholestanol and Lathosterol among Italian unaffected newborns, children and healthy adults. The sterols were extracted from 130 plasma samples (24 newborns, 33 children and 73 adults) by a liquid-liquid separation method and quantified by gas chromatography coupled with a flame ionization detector. Cholesterol, cholestanol and Lathosterol levels together with the cholestanol/cholesterol and Lathosterol/cholesterol ratios are statistically different among the three groups. Cholesterol levels progressively increased from newborns to children and to adults, whereas cholestanol/cholesterol and cholestanol/Lathosterol ratios progressively decreased from newborns to children and to adults. Lathosterol levels were higher in adults than in both newborns and children. In the total population a positive correlation was observed between cholesterol levels and both cholestanol (correlation coefficient = 0.290, p = 0.001) and Lathosterol levels (correlation coefficient = 0.353, p <  0.0001). Although this study can only be considered an explorative experience due to the low number of analyzed samples, we revealed several differences of plasma cholestanol and Lathosterol levels and their ratios to cholesterol levels among newborns, children and adults. These evidences indicate the need of age-related reference values of cholestanol and Lathosterol concentrations, including also newborns and children.

  • Lathosterolosis a novel multiple malformation mental retardation syndrome due to deficiency of 3β hydroxysteroid δ5 desaturase
    American Journal of Human Genetics, 2002
    Co-Authors: Nicola Brunettipierri, Gaetano Corso, Antonio Dello Russo, Massimiliano Rossi, Paola Ferrari, F Balli, Francesco Rivasi, Ida Annunziata, Andrea Ballabio, Generoso Andria
    Abstract:

    We report the clinical, biochemical, and molecular characterization of a patient with a novel defect of cholesterol biosynthesis. This patient presented with a complex phenotype, including multiple congenital anomalies, mental retardation, and liver disease. In the patient’s plasma and cells, we found increased levels of Lathosterol. The biosynthesis of cholesterol in the patient’s fibroblasts was defective, showing a block in the conversion of Lathosterol into 7-dehydrocholesterol. The activity of 3β-hydroxysteroid-Δ5-desaturase (SC5D), the enzyme involved in this reaction, was deficient in the patient’s fibroblasts. Sequence analysis of the SC5D gene in the patient’s DNA, showing the presence of two missense mutations (R29Q and G211D), confirmed that the patient is affected by a novel defect of cholesterol biosynthesis.

Jay D Horton - One of the best experts on this subject based on the ideXlab platform.

  • fasting reduces plasma proprotein convertase subtilisin kexin type 9 and cholesterol biosynthesis in humans
    Journal of Lipid Research, 2010
    Co-Authors: Jeffrey D Browning, Jay D Horton
    Abstract:

    Proprotein convertase, subtilisin/kexin type 9 (PCSK9), a key regulator of plasma LDL-cholesterol (LDL-c) and cardiovascular risk, is produced in liver and secreted into plasma where it binds hepatic LDL receptors (LDLR), leading to their degradation. PCSK9 is transcriptionally activated by sterol response element-binding protein (SREBP)-2, a transcription factor that also activates all genes for cholesterol synthesis as well as the LDLR. Here we investigated the relationship between plasma PCSK9 levels and the Lathosterol-to-cholesterol ratio, a marker of cholesterol biosynthesis, in 18 healthy subjects during a 48 h fast. In all individuals, plasma PCSK9 levels declined steadily during the fasting period, reaching a nadir at 36 h that was ∼58% lower than levels measured in the fed state (P < 0.001). Similarly, the Lathosterol-to-cholesterol ratio declined in parallel with plasma PCSK9 concentrations during the fast, reaching a nadir at 36 h that was ∼28% lower than that measured in the fed state (P = 0.024). In summary, fasting has a marked effect on plasma PCSK9 concentrations, which is mirrored by measures of cholesterol synthesis in humans. Inasmuch as cholesterol synthesis and PCSK9 are both regulated by SREBP-2, these results suggest that plasma PCSK9 levels may serve as a surrogate marker of hepatic SREBP-2 activity in humans.