RESUMO
Skeletal muscle is critical for mobility and many metabolic functions integral to survival and long-term health. Alcohol can affect skeletal muscle physiology and metabolism, which will have immediate and long-term consequences on health. While skeletal muscle abnormalities, including morphological, biochemical, and functional impairments, are well-documented in adults that excessively consume alcohol, there is a scarcity of information about the skeletal muscle in the offspring prenatally exposed to alcohol ("prenatal alcohol exposure"; PAE). This minireview examines the available studies addressing skeletal muscle abnormalities due to PAE. Growth restriction, fetal alcohol myopathy, and abnormalities in the neuromuscular system, which contribute to deficits in locomotion, are some direct, immediate consequences of PAE on skeletal muscle morphology and function. Long-term health consequences of PAE-related skeletal abnormalities include impaired glucose metabolism in the skeletal muscle, resulting in glucose intolerance and insulin resistance, leading to an increased risk of type 2 diabetes. In general, there is limited information on the morphological, biochemical, and functional features of skeletal abnormalities in PAE offspring. There is a need to understand how PAE affects muscle growth and function at the cellular level during early development to improve the immediate and long-term health of offspring suffering from PAE.
Assuntos
Transtornos do Espectro Alcoólico Fetal/metabolismo , Intolerância à Glucose , Glucose/metabolismo , Transtornos do Crescimento/metabolismo , Músculo Esquelético/metabolismo , Doenças Neuromusculares/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/terapia , Transtornos do Espectro Alcoólico Fetal/patologia , Transtornos do Espectro Alcoólico Fetal/terapia , Transtornos do Crescimento/patologia , Transtornos do Crescimento/terapia , Humanos , Resistência à Insulina , Músculo Esquelético/anormalidades , Músculo Esquelético/patologia , Doenças Neuromusculares/patologia , Doenças Neuromusculares/terapiaRESUMO
OBJECTIVES: To assess the association between biomarkers of thyroid status and 5α-stanols in patients with sitosterolemia treated with ezetimibe (EZE). STUDY DESIGN: Eight patients with sitosterolemia (16-56 years of age) were studied during 14 weeks off EZE therapy and 14 weeks on EZE (10 mg/day). Serum thyroid biomarkers (free triiodothyronine [FT3], free thyroxine [FT4], FT3/FT4 ratio, thyroid-stimulating hormone), 5α-stanols (sitostanol and cholestanol), and cholestanol precursors (total cholesterol and its synthesis marker lathosterol, and 7α-hydroxy-4-cholesten-3-one cholestenol) were measured at baseline and during the 14 weeks off EZE and on EZE. RESULTS: EZE increased FT3/FT4 (10% ± 4%; P = .02). EZE reduced plasma and red blood cells sitostanol (-38% ± 6% and -20% ± 4%; all P < .05) and cholestanol (-18% ± 6% and -13% ± 3%; all P < .05). The change in plasma cholestanol level on EZE inversely correlated with the change in FT3/FT4 (r = -0.86; P = .01). EZE lowered total cholesterol (P < .0001) and did not affect 7α-hydroxy-4-cholesten-3-one cholestanol. EZE increased (P < .0001) lathosterol initially, but the level was not sustained, resulting in similar levels at week 14 off EZE and on EZE. CONCLUSION: In patients with STSL, 5α-stanols levels might be associated with thyroid function. EZE reduces circulating 5α-stanols while increasing FT3/FT4, implying increased conversion of T4 to T3, thus possibly improving thyroid hormone status. TRIAL REGISTRATION: ClinicalTrials.govNCT01584206.
Assuntos
Anticolesterolemiantes/uso terapêutico , Ezetimiba/uso terapêutico , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Enteropatias/sangue , Enteropatias/tratamento farmacológico , Erros Inatos do Metabolismo Lipídico/sangue , Erros Inatos do Metabolismo Lipídico/tratamento farmacológico , Fitosteróis/efeitos adversos , Adolescente , Adulto , Colestanol/sangue , Colestenonas/sangue , Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fitosteróis/sangue , Sitosteroides/sangue , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto JovemRESUMO
OBJECTIVE: To assess if ezetimibe (EZE), a sterol-absorption inhibitor, improves platelet (PLT) count and size relative to its effect on plasma plant sterol (PS) in patients with sitosterolemia (STSL). STUDY DESIGN: Patients with STSL (5 males, 3 females, 16-56 years of age) receiving EZE intervention as part of their routine care participated in this study. EZE was discontinued for 14 weeks (off) and then resumed for another 14 weeks (on). Hematology variables along with plasma and red blood cells (RBC) PS and total cholesterol (TC) levels were measured at the end of each phase. RESULTS: EZE increased PLT count (23% ± 9%) and decreased mean PLT volume (MPV; 10% ± 3%, all P < .05). In patients off EZE, PLT counts inversely correlated (r = -0.96 and r = -0.91, all P < .01) with plasma and RBC PS to TC ratio (PS/TC), and MPV positively correlated (r = 0.91, P = .03 and r = 0.93, P = .02) with plasma and RBC PS/TC. EZE reduced plasma and RBC sitosterol (-35% ± 4% and -28% ± 3%), total PS (-37% ± 4% and -28% ± 3%, all P < .0001) levels, and PS/TC (-27% ± 4% and -28% ± 4%, P < .01). CONCLUSIONS: EZE reduces plasma and RBC PS levels, while increasing PLT count and decreasing MPV, and thereby may reduce the risk for bleeding in STSL. Plasma PS levels and ABCG5/ABCG8 genes should be analyzed in patients with unexplained hematologic abnormalities.
Assuntos
Anticolesterolemiantes/uso terapêutico , Azetidinas/uso terapêutico , Colesterol/sangue , Hipercolesterolemia/tratamento farmacológico , Enteropatias/tratamento farmacológico , Erros Inatos do Metabolismo Lipídico/tratamento farmacológico , Fitosteróis/efeitos adversos , Fitosteróis/sangue , Contagem de Plaquetas , Adolescente , Adulto , Anticolesterolemiantes/administração & dosagem , Azetidinas/administração & dosagem , Canadá , Contagem de Eritrócitos , Ezetimiba , Feminino , Humanos , Hipercolesterolemia/sangue , Enteropatias/sangue , Erros Inatos do Metabolismo Lipídico/sangue , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento , Estados Unidos , Adulto JovemRESUMO
Phytosterolemia (sitosterolemia) is a rare autosomal recessive sterol storage disease caused by mutations in either of the adenosine triphosphate (ATP) binding cassette transporter genes; (ABC) G5 or ABCG8, leading to impaired elimination of plant sterols and stanols, with their increased accumulation in the blood and tissues. Thus the disease is characterized by substantially elevated serum plant sterols and stanols, with moderate to high plasma cholesterol levels, and increased risk of premature atherosclerosis. Hematologic abnormalities including macrothrombocytopenia, stomatocytosis and hemolysis are frequently observed in sitosterolemia patients. Currently, ezetimibe, a sterol absorption inhibitor, is used as the routine treatment for sitosterolemia, with reported improvement in plant sterol levels and hemolytic parameters. This review summarizes the research related to the health impact of plant sterols and stanols on sitosterolemia.
Assuntos
Hipercolesterolemia/sangue , Hipercolesterolemia/genética , Enteropatias/sangue , Enteropatias/genética , Erros Inatos do Metabolismo Lipídico/sangue , Erros Inatos do Metabolismo Lipídico/genética , Fitosteróis/efeitos adversos , Fitosteróis/sangue , Plantas/química , Transportadores de Cassetes de Ligação de ATP/genética , Humanos , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/metabolismo , Enteropatias/tratamento farmacológico , Enteropatias/metabolismo , Erros Inatos do Metabolismo Lipídico/tratamento farmacológico , Erros Inatos do Metabolismo Lipídico/metabolismo , Mutação , Fitosteróis/genética , Fitosteróis/metabolismoRESUMO
Current global estimation suggests that about 10% of adults worldwide have diabetes, thus, various strategies are needed to address the issue, including dietary factors such as vitamin D. Various studies have suggested an inverse associations between vitamin D and the risks and pathogenesis of all forms of diabetes (type 1, type 2 and gestational diabetes). The underlying mechanism is not fully understood; however, the expression of vitamin D receptors in pancreatic beta cells suggests an important physiological role for vitamin D in beta cell function. Vitamin D deficiency may impair blood glucose control and decrease insulin sensitivity by reducing insulin secretion from beta cells. Many studies suggest that vitamin D intervention may be beneficial; however, there is inconclusive evidence of the effectiveness of vitamin D supplementation on reducing the risks or managing the pathogenesis of all forms of diabetes. Part of the pathogenesis of vitamin D for reducing diabetes is thought to be related to its impact on gut microbiota profile, via the suggested prebiotic properties of vitamin D.
Assuntos
Microbioma Gastrointestinal , Resistência à Insulina , Deficiência de Vitamina D , Vitamina D , Humanos , Vitamina D/farmacologia , Vitamina D/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Diabetes Mellitus/prevenção & controle , Suplementos NutricionaisRESUMO
We previously demonstrated that intra-uterine growth-restricted (IUGR) Yucatan miniature pigs develop modestly elevated blood pressure (BP) as young adults. The present study evaluated the effects of a post-weaning Western-style, high-salt-fat-sugar (HSFS) diet on early programming of BP. IUGR piglets (3 d old, 0·77 (sem 0·04) kg, n 6) were paired with normal weight (NW) same-sex littermates (1·14 (sem 0·03) kg, n 6) and fed milk replacer for 4 weeks. A third littermate was left with the sow (SF; 1·01 (sem 0·05) kg, n 6). When 4 weeks old, all pigs were placed on a HSFS diet ad libitum for 5 h/d. When 11 months old, telemeters were implanted to measure BP in pigs before (4·5% NaCl) and after (0·5% NaCl) a 7 d reduced salt challenge. At necropsy, nephron numbers were determined. Before sexual maturity, IUGR pigs had greater relative feed intake (P<0·05), and experienced catch-up growth with greater adiposity, with correlations between adiposity and BP (P<0·05). Adult IUGR pigs had 26-34% fewer nephrons and higher diastolic BP (107·7 (sem 4·9) mmHg, P = 0·044) than NW (97·2 (sem 1·8) mmHg) and SF (98·9 (sem 5·3) mmHg) pigs. Systolic BP was similar among the three groups, but was significantly elevated compared with levels previously reported for a control diet. Salt restriction reduced BP in all groups (P<0·05), but with no differences (P>0·05) in the degree of salt sensitivity among groups. In conclusion, a post-weaning Western-style diet exacerbates early programming of diastolic BP in Yucatan miniature swine, whereas systolic BP is more sensitive to postnatal diet.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Sacarose Alimentar/efeitos adversos , Modelos Animais de Doenças , Desenvolvimento Fetal , Retardo do Crescimento Fetal/fisiopatologia , Hipertensão/etiologia , Cloreto de Sódio na Dieta/efeitos adversos , Adiposidade , Animais , Animais Endogâmicos , Doenças Cardiovasculares/etiologia , Dieta Hipossódica , Ingestão de Energia , Feminino , Hipertensão/dietoterapia , Hipertensão/patologia , Masculino , Néfrons/patologia , Suínos , Porco Miniatura , Desmame , Aumento de PesoRESUMO
Calcium is well known to be integral to bone and muscle health, with deleterious effects such as osteoporosis associated with inadequate calcium intake. Recent studies have also highlighted the significant effects of calcium in extra-musculoskeletal functioning, including the cardiovascular system, obesity, and cancer. Calcium impacts the cardiovascular system as an antagonist associated with a reduction in hypertension, increase vasodilation, and improvement in blood vessel function when obtained in the diet as an organic source, through food. However, the inorganic source of calcium, found in supplements, may be negatively associated with the cardiovascular system due to plaque deposits and atherogenesis when taken in excess. Some studies suggest that calcium intake may impact obesity by regulation of adipogenesis and reducing fat deposits with resulting weight loss. The pathogenesis of calcium for reducing obesity is thought to be related in part to its impact on gut microbiota profile, with the suggestion that calcium may have prebiotic properties. Animal and some human studies propose that calcium may also have a role in cancer prevention and/or treatment due to its function in the cell proliferation process and the impact on hormonal regulation, and thus warrants more investigations in the human population. Some prospective and small clinical studies suggest that calcium may be beneficial for colorectal cancer. Overall, emerging research in various areas continues to highlight the essentiality of dietary calcium for functioning at the molecular and biochemical level toward improvement in health and some chronic disease conditions.
Assuntos
Sistema Cardiovascular , Neoplasias , Animais , Cálcio da Dieta , Suplementos Nutricionais , Humanos , Obesidade , Estudos ProspectivosRESUMO
Cardiovascular disease (CVD) is a leading cause of death worldwide. Elevated concentrations of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are major lipid biomarkers that contribute to the risk of CVD. Phytosterols well known for their cholesterol-lowering ability, are non-nutritive compounds that are naturally found in plant-based foods and can be classified into plant sterols and plant stanols. Numerous clinical trials demonstrated that 2 g phytosterols per day have LDL-C lowering efficacy ranges of 8-10%. Some observational studies also showed an inverse association between phytosterols and LDL-C reduction. Beyond the cholesterol-lowering beneficial effects of phytosterols, the association of phytosterols with CVD risk events such as coronary artery disease and premature atherosclerosis in sitosterolemia patients have also been reported. Furthermore, there is an increasing demand to determine the association of circulating phytosterols with vascular health biomarkers such as arterial stiffness biomarkers. Therefore, this review aims to examine the ability of phytosterols for CVD risk prevention by reviewing the current data that looks at the association between dietary phytosterols intake and serum lipid biomarkers, and the impact of circulating phytosterols level on vascular health biomarkers. The clinical studies in which the impact of phytosterols on vascular function is investigated show minor but beneficial phytosterols effects over vascular health. The aforementioned vascular health biomarkers are pulse wave velocity, augmentation index, and arterial blood pressure. The current review will serve to begin to address the research gap that exists between the association of dietary phytosterols with CVD risk biomarkers.
Assuntos
Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/prevenção & controle , Fitosteróis/sangue , Fitosteróis/farmacologia , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Colesterol/sangue , Dieta , Alimentos , Humanos , Fitosteróis/classificaçãoRESUMO
Serum concentrations of lathosterol, the plant sterols campesterol and sitosterol and the cholesterol metabolite 5α-cholestanol are widely used as surrogate markers of cholesterol synthesis and absorption, respectively. Increasing numbers of laboratories utilize a broad spectrum of well-established and recently developed methods for the determination of cholesterol and non-cholesterol sterols (NCS). In order to evaluate the quality of these measurements and to identify possible sources of analytical errors our group initiated the first international survey for cholesterol and NCS. The cholesterol and NCS survey was structured as a two-part survey which took place in the years 2013 and 2014. The first survey part was designed as descriptive, providing information about the variation of reported results from different laboratories. A set of two lyophilized pooled sera (A and B) was sent to twenty laboratories specialized in chromatographic lipid analysis. The different sterols were quantified either by gas chromatography-flame ionization detection, gas chromatography- or liquid chromatography-mass selective detection. The participants were requested to determine cholesterol and NCS concentrations in the provided samples as part of their normal laboratory routine. The second part was designed as interventional survey. Twenty-two laboratories agreed to participate and received again two different lyophilized pooled sera (C and D). In contrast to the first international survey, each participant received standard stock solutions with defined concentrations of cholesterol and NCS. The participants were requested to use diluted calibration solutions from the provided standard stock solutions for quantification of cholesterol and NCS. In both surveys, each laboratory used its own internal standard (5α-cholestane, epicoprostanol or deuterium labelled sterols). Main outcome of the survey was, that unacceptably high interlaboratory variations for cholesterol and NCS concentrations are reported, even when the individual laboratories used the same calibration material. We discuss different sources of errors and recommend all laboratories analysing cholesterol and NCS to participate in regular quality control programs.
Assuntos
Colesterol/sangue , Fitosteróis/sangue , Colestanol/sangue , Colesterol/análogos & derivados , Cromatografia Gasosa/métodos , Cromatografia Líquida/métodos , Humanos , Sitosteroides/sangue , Inquéritos e QuestionáriosRESUMO
The purpose of this study was to evaluate the effectiveness of 3.0 g/d of omega-3 fatty acid (eicosapentaenoic acid and docosahexaenoic acid) supplementation combined with progressive resistance training to improve body composition and lower inflammatory cytokines in older men when compared to placebo and resistance training. We hypothesized that completing a 12-week omega-3 supplementation period along with whole body resistance exercise (3 times/wk) would result in a significantly greater improvement in lean tissue mass as well as a significant decrease in interleukin-6 and tumor necrosis factor-α when compared to placebo. A total of 23 older men (≥65â¯years old) were randomized to an omega-3 supplementation group (nâ¯=â¯11) or placebo group (nâ¯=â¯12), and all the participants completed the same whole body progressive resistance training program. Baseline and 12-week data collection included body composition, muscle strength, functional ability, and inflammatory cytokines. Results indicated a significant main effect for time (all Pâ¯<â¯.05) for percent body fat (-2.5%), lean tissue mass (+1.1%), lumbar bone mineral density (+1.1%), hip bone mineral content (+1.1%), chest press strength (+31%), leg press strength (+37%), timed-up-and-go (-6.6%), and 6-minute walk distance (+4.5%) from baseline to post 12â¯weeks. No significant effects were noted for the 2 inflammatory cytokines measured (Pâ¯>â¯.05). We conclude that progressive resistance training exercise is an excellent method to enhance parameters of body composition, skeletal muscle strength, and functional ability in older men, whereas omega-3 supplementation did nothing to enhance these parameters or influence inflammatory biomarkers.
Assuntos
Composição Corporal/efeitos dos fármacos , Citocinas/sangue , Suplementos Nutricionais , Ácidos Graxos Ômega-3/farmacologia , Inflamação/sangue , Músculo Esquelético/efeitos dos fármacos , Treinamento Resistido , Tecido Adiposo/metabolismo , Idoso , Biomarcadores/sangue , Compartimentos de Líquidos Corporais/metabolismo , Densidade Óssea/efeitos dos fármacos , Exercício Físico , Humanos , Masculino , Força Muscular/efeitos dos fármacos , Músculo Esquelético/fisiologia , Desempenho Físico FuncionalRESUMO
Current evidence indicates that foods with added plant sterols or stanols can lower serum levels of low-density lipoprotein cholesterol. This review summarizes the recent findings and deliberations of 31 experts in the field who participated in a scientific meeting in Winnipeg, Canada, on the health effects of plant sterols and stanols. Participants discussed issues including, but not limited to, the health benefits of plant sterols and stanols beyond cholesterol lowering, the role of plant sterols and stanols as adjuncts to diet and drugs, and the challenges involved in measuring plant sterols and stanols in biological samples. Variations in interindividual responses to plant sterols and stanols, as well as the personalization of lipid-lowering therapies, were addressed. Finally, the clinical aspects and treatment of sitosterolemia were reviewed. Although plant sterols and stanols continue to offer an efficacious and convenient dietary approach to cholesterol management, long-term clinical trials investigating the endpoints of cardiovascular disease are still lacking.
Assuntos
Anticolesterolemiantes/farmacologia , Doenças Cardiovasculares/terapia , Dieta/métodos , Hipercolesterolemia/terapia , Enteropatias/terapia , Erros Inatos do Metabolismo Lipídico/terapia , Fitosteróis/efeitos adversos , Fitosteróis/farmacologia , Canadá , Doenças Cardiovasculares/sangue , Colesterol/sangue , LDL-Colesterol/sangue , Congressos como Assunto , Humanos , Hipercolesterolemia/sangue , Enteropatias/sangue , Erros Inatos do Metabolismo Lipídico/sangue , Fitosteróis/sangueRESUMO
Creatine, a very popular supplement among athletic populations, is of growing interest for clinical applications. Since over 90% of creatine is stored in skeletal muscle, the effect of creatine supplementation on muscle metabolism is a widely studied area. While numerous studies over the past few decades have shown that creatine supplementation has many favorable effects on skeletal muscle physiology and metabolism, including enhancing muscle mass (growth/hypertrophy); the underlying mechanisms are poorly understood. This report reviews studies addressing the mechanisms of action of creatine supplementation on skeletal muscle growth/hypertrophy. Early research proposed that the osmotic effect of creatine supplementation serves as a cellular stressor (osmosensing) that acts as an anabolic stimulus for protein synthesis signal pathways. Other reports indicated that creatine directly affects muscle protein synthesis via modulations of components in the mammalian target of rapamycin (mTOR) pathway. Creatine may also directly affect the myogenic process (formation of muscle tissue), by altering secretions of myokines, such as myostatin and insulin-like growth factor-1, and expressions of myogenic regulatory factors, resulting in enhanced satellite cells mitotic activities and differentiation into myofiber. Overall, there is still no clear understanding of the mechanisms of action regarding how creatine affects muscle mass/growth, but current evidence suggests it may exert its effects through multiple approaches, with converging impacts on protein synthesis and myogenesis.
Assuntos
Creatina/administração & dosagem , Suplementos Nutricionais , Desenvolvimento Muscular/efeitos dos fármacos , Fatores de Regulação Miogênica/genética , Biossíntese de Proteínas/efeitos dos fármacos , Animais , Diferenciação Celular , Regulação da Expressão Gênica , Humanos , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Células Musculares/citologia , Células Musculares/metabolismo , Desenvolvimento Muscular/genética , Músculo Esquelético/citologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Fatores de Regulação Miogênica/agonistas , Fatores de Regulação Miogênica/metabolismo , Miostatina/genética , Miostatina/metabolismo , Biossíntese de Proteínas/genética , Células Satélites de Músculo Esquelético/citologia , Células Satélites de Músculo Esquelético/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND AND AIMS: Sitosterolemia displays high plasma total sterols [high plant sterols (PS) + normal to high total cholesterol (TC)] with normal to moderately elevated low-density lipoprotein (LDL) levels. High LDL, intermediate-density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, low high-density lipoprotein (HDL), and increased non-HDL and the ratios of TC and triglycerides (TG) to HDL can increase the risk for atherosclerosis. Ezetimibe (EZE) can reduce plasma PS and TC levels in sitosterolemia, but its effect on lipoprotein subclasses has not been previously reported. METHODS: Sitosterolemia patients (n = 8) were taken off EZE for 14 weeks (OFF EZE) and placed on EZE (10 mg/d) for 14 weeks (ON EZE). Serum lipids were measured enzymatically and lipoprotein subclasses were assessed by polyacrylamide gel electrophoresis. RESULTS: EZE reduced (p < 0.05) total sterols (-12.5 ± 4.1%) and LDL-sterol (-22.7 ± 5.7%) and its sterol mass of large VLDL (-24.4 ± 4.5%), VLDL remnants (-21.1 ± 7.9%) and large IDL (-22.4 ± 7.2%) compared to OFF EZE. EZE did not affect large LDL subclasses or mean LDL particle size (273.8 ± 0.6 vs. 274.6 ± 0.3 Å). EZE increased HDL-sterol (25.5 ± 8.0%, p = 0.008) including intermediate (34 ± 14%, p = 0.02) and large (33 ± 16%, p = 0.06) HDL. EZE reduced non-HDL-sterol (-21.8± 5.0%), total sterols/HDL (-28.2 ± 5.5%) and TG/HDL (-27.4 ± 6.5%, all p < 0.01). CONCLUSIONS: EZE improves VLDL and HDL subfraction distribution, thereby reducing the atherogenic lipid profile, thus providing potential clinical benefit in sitosterolemia beyond TC and PS reduction.
Assuntos
Ezetimiba/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Enteropatias/tratamento farmacológico , Erros Inatos do Metabolismo Lipídico/tratamento farmacológico , Lipoproteínas HDL/sangue , Lipoproteínas VLDL/sangue , Fitosteróis/efeitos adversos , Adolescente , Adulto , Anticolesterolemiantes/uso terapêutico , HDL-Colesterol/sangue , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Hipercolesterolemia/sangue , Enteropatias/sangue , Erros Inatos do Metabolismo Lipídico/sangue , Lipoproteínas HDL/efeitos dos fármacos , Lipoproteínas IDL/sangue , Lipoproteínas IDL/efeitos dos fármacos , Lipoproteínas VLDL/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Fitosteróis/sangue , Resultado do Tratamento , Adulto JovemRESUMO
Early nutrition has critical influences on cardiovascular disease risk in adulthood. The study objectives were to evaluate the impact of low birth weight on fasting and postprandial lipid metabolism and endothelium function in Yucatan miniature pigs. Intrauterine growth-restricted (IUGR) piglets (n = 6; 3 days old, 0.73 ± 0.04 kg) were paired with normal-weight (NW) same-sex littermates (n = 6; 1.11 ± 0.05 kg) and fed milk replacer ad libitum for 4 weeks. Thereafter, all pigs were fed a standard diet ad libitum for 5 h/day with growth, intakes, and blood samples collected for 8 months. At 9 months old, pigs were surgically fitted with venous catheters and an oral fat tolerance test was performed. At 10 months old, pigs were killed and endothelium-dependent and -independent vasodilations of isolated coronary arteries were measured using wire-myographs. IUGR pigs demonstrated catch-up growth (P < 0.05) in body weight and abdominal circumference prior to sexual maturity (<7 months old) and had more (P < 0.05) subcutaneous fat at 10 months old compared with NW pigs. IUGR pigs had consistently higher fasting plasma triglyceride concentrations from 5 to 10 months old and higher liver triglyceride and total cholesterol concentrations at 10 months old (P < 0.05). The fat tolerance test revealed delayed postprandial triglyceride clearance in IUGR pigs, but no differences in plaque formation or vascular reactivity. To conclude, IUGR and early postnatal catch-up growth are associated with increased overall body fat deposition and altered triglyceride metabolism in adult Yucatan miniature swine.
Assuntos
Adiposidade/fisiologia , Retardo do Crescimento Fetal/veterinária , Metabolismo dos Lipídeos/fisiologia , Suínos/crescimento & desenvolvimento , Animais , Animais Recém-Nascidos , Dieta , Feminino , Masculino , Porco MiniaturaRESUMO
Non-cholesterol sterols (NCS) are used as surrogate markers of cholesterol metabolism which can be measured from a single blood sample. Cholesterol precursors are used as markers of endogenous cholesterol synthesis and plant sterols are used as markers of cholesterol absorption. However, most aspects of NCS analysis show wide variability among researchers within the area of biomedical research. This variability in methodology is a significant contributor to variation between reported NCS values and hampers the confidence in comparing NCS values across different research groups, as well as the ability to conduct meta-analyses. This paper summarizes the considerations and conclusions of a workshop where academic and industrial experts met to discuss NCS measurement. Highlighted is why each step in the analysis of NCS merits critical consideration, with the hopes of moving toward more standardized and comparable NCS analysis methodologies. Alkaline hydrolysis and liquid-liquid extraction of NCS followed by parallel detection on GC-FID and GC-MS is proposed as an ideal methodology for the bio-analysis of NCS. Furthermore the importance of cross-comparison or round robin testing between various groups who measure NCS is critical to the standardization of NCS measurement.
Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Extração Líquido-Líquido/métodos , Esteróis/química , Fitosteróis/análise , Fitosteróis/química , Fitosteróis/isolamento & purificação , Esteróis/análise , Esteróis/isolamento & purificaçãoRESUMO
Sitosterolemia (STSL) is a rare autosomal recessive disease, manifested by extremely elevated plant sterols (PS) in plasma and tissue, leading to xanthoma and premature atherosclerotic disease. Therapeutic approaches include limiting PS intake, interrupting enterohepatic circulation of bile acid using bile acid binding resins such as cholestyramine, and/or ileal bypass, and inhibiting intestinal sterol absorption by ezetimibe (EZE). The objective of this review is to evaluate sterol metabolism in STSL and the impact of the currently available treatments on sterol trafficking in this disease. The role of PS in initiation of xanthomas and premature atherosclerosis is also discussed. Blocking sterols absorption with EZE has revolutionized STSL patient treatment as it reduces circulating levels of non-cholesterol sterols in STSL. However, none of the available treatments including EZE have normalized plasma PS concentrations. Future studies are needed to: (i) explore where cholesterol and non-cholesterol sterols accumulate, (ii) assess to what extent these sterols in tissues can be mobilized after blocking their absorption, and (iii) define the factors governing sterol flux.
Assuntos
Aterosclerose/tratamento farmacológico , Azetidinas/farmacologia , Colesterol/sangue , Hipercolesterolemia/metabolismo , Enteropatias/metabolismo , Erros Inatos do Metabolismo Lipídico/metabolismo , Fitosteróis/efeitos adversos , Esteróis/sangue , Xantomatose/tratamento farmacológico , Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/metabolismo , Absorção , Colesterol/metabolismo , Progressão da Doença , Ezetimiba , Humanos , Hipercolesterolemia/sangue , Enteropatias/sangue , Cinética , Erros Inatos do Metabolismo Lipídico/sangue , Proteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras , Fitosteróis/sangue , Fitosteróis/metabolismo , Sitosteroides/sangue , Esterol O-Aciltransferase/metabolismo , Esteróis/metabolismo , Esterol O-Aciltransferase 2RESUMO
BACKGROUND: Plant sterol (PS) supplementation is increasingly accepted as a dietary strategy to lower plasma cholesterol concentrations. However, information is scarce about the effect of increased PS intake in potentially vulnerable groups, such as phytosterolemia heterozygotes (HET). OBJECTIVE: This study assessed the responsiveness of circulating PS and lipid concentrations and cholesterol kinetics (absorption and synthesis) to daily PS supplementation in HET (ABCG8 S107X mutation) compared with a healthy control cohort. DESIGN: A double-blind, randomized, crossover, placebo-controlled study was conducted in 10 HET and 15 control subjects. The participants had a mean (±SEM) age of 34 ± 2 y and a BMI (in kg/m²) of 29.9 ± 1.1 and consumed â¼1.6 g PS or placebo capsules daily with supper for 4 wk. Cholesterol absorption and synthesis were assessed by using [¹³C]cholesterol and deuterium oxide, respectively. RESULTS: Plasma LDL-cholesterol concentrations decreased (P = 0.006) in both groups after PS supplementation (HET: 2.73 ± 0.19 mmol/L; control: 3.11 ± 0.19 mmol/L) compared with placebo (HET: 3.12 ± 0.20 mmol/L; control: 3.50 ± 0.21 mmol/L), whereas PS concentrations (campesterol+ß-sitosterol) increased (P = 0.03) in both groups after PS supplementation (HET: 39.72 ± 6.05 µmol/L; control: 24.03 ± 1.65 µmol/L) compared with placebo (HET: 27.32 ± 3.80 µmol/L; control: 21.12 ± 2.05 µmol/L). Cholesterol absorption efficiency decreased (P = 0.010) by â¼22% and â¼17% and synthesis rates increased (P = 0.040) by â¼20% and â¼24% in the HET and control groups, respectively, in response to PS consumption compared with placebo. CONCLUSION: These data suggest that heterozygosity for the ABCG8 S107X mutation does not influence the action of dietary PS on circulating cholesterol concentrations but may affect sterol absorption.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Colesterol/metabolismo , Suplementos Nutricionais , Hipercolesterolemia/dietoterapia , Enteropatias/dietoterapia , Erros Inatos do Metabolismo Lipídico/dietoterapia , Lipídeos/sangue , Fitosteróis/uso terapêutico , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/química , Adolescente , Adulto , Idoso , Substituição de Aminoácidos , Colesterol/biossíntese , Colesterol/sangue , Estudos de Coortes , Estudos Cross-Over , Método Duplo-Cego , Feminino , Heterozigoto , Humanos , Hipercolesterolemia/etiologia , Hipercolesterolemia/genética , Hipercolesterolemia/metabolismo , Hipercolesterolemia/fisiopatologia , Hipercolesterolemia/prevenção & controle , Absorção Intestinal , Enteropatias/genética , Enteropatias/metabolismo , Enteropatias/fisiopatologia , Cinética , Erros Inatos do Metabolismo Lipídico/genética , Erros Inatos do Metabolismo Lipídico/metabolismo , Erros Inatos do Metabolismo Lipídico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Proteínas Mutantes/química , Proteínas Mutantes/genética , Fitosteróis/efeitos adversos , Fitosteróis/sangue , Fitosteróis/genética , Fitosteróis/metabolismo , Adulto JovemRESUMO
Radiotelemetry was used to evaluate diet-related elevation of blood pressure in adult Yucatan miniature swine. Systolic arterial blood pressure (SAP), diastolic atrial blood pressure (DAP), heart rate, and locomotor activity were assessed in 9- or 11-mo-old Yucatan miniature pigs fed a standard diet or a North American-type diet high in salt, fat, and sugar (HSFS). Compared with pigs fed standard diet, pigs fed HSFS diet showed markedly elevated SAP (132 ± 3 compared with 156 ± 6 mm Hg), whereas DAP was unchanged (92 ± 2 compared with 99 ± 5 mm Hg). In addition, all pigs were modestly sensitive to short-term changes in dietary salt, as indicated by a 6% to 7% response in blood pressure parameters. According to these data, the increase in SAP for pigs on the HSFS diet was too large to be explained by the NaCl content of the diet alone. We found no evidence of endothelial dysfunction, and the relaxation responses of isolated coronary arteries actually were enhanced in the HSFS group. In conclusion, in a Yucatan miniature pigs model chronically fed a HSFS diet, DAP did not increase, but SAP and pulse pressure appeared to be affected by high dietary levels of fat or sugar (or both).
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Sacarose Alimentar/efeitos adversos , Cloreto de Sódio na Dieta/efeitos adversos , Porco Miniatura , Animais , Frequência Cardíaca/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Suínos , Telemetria/veterináriaRESUMO
Epidemiological studies have linked small birth weight and lack of breastfeeding to type 2 diabetes mellitus. This study aimed to determine if (i) small birth weight promotes and (ii) suckling prevents the development of adiposity and diabetes biomarkers in a Yucatan miniature pig model. At 3 days of age, the intrauterine growth-restricted (IUGR) piglet (n = 6) was paired with a normal weight (NW), same-sex littermate (n = 6) and fed milk replacer for 4 weeks. A sow-fed normal weight littermate (n = 6) was also compared with the NW littermate to assess the effects of suckling. All pigs were fed a standard diet ad libitum for 5 h·day(-1) from week 4. At 9.5 months, pigs underwent intravenous glucose tolerance (IVGTT) and insulin sensitivity tests (IST). At 10 months, tissues were harvested for fat analysis and pancreas histology. IUGR pigs demonstrated compensatory growth before sexual maturity and had greater subcutaneous fat depth; birth weight also negatively correlated with visceral fat content. Visceral and subcutaneous adiposity were greater in females than males. IVGTT and IST outcomes were not different due to birth weight or suckling. However, visceral adiposity was associated with several glucose tolerance outcomes and females were more glucose intolerant due to their greater adiposity. Pancreas insulin content or histology outcomes were not different. This model did not develop markers of type 2 diabetes mellitus because of small birth weight or formula feeding. However, visceral adiposity and sex were associated with glucose intolerance, which is consistent with data in humans.
Assuntos
Adiposidade , Peso ao Nascer , Diabetes Mellitus Tipo 2/etiologia , Intolerância à Glucose/etiologia , Gordura Intra-Abdominal/fisiopatologia , Fatores Etários , Envelhecimento , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Recém-Nascidos , Animais Lactentes , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Retardo do Crescimento Fetal , Alimentos Formulados , Intolerância à Glucose/sangue , Intolerância à Glucose/fisiopatologia , Teste de Tolerância a Glucose , Insulina/sangue , Resistência à Insulina , Modelos Lineares , Masculino , Pâncreas/metabolismo , Medição de Risco , Fatores de Risco , Fatores Sexuais , Suínos , Porco Miniatura , Aumento de PesoRESUMO
BACKGROUND: Impaired fetal growth and rapid postnatal growth are associated with programming of hypertension and metabolic syndrome in adulthood. OBJECTIVES: This study evaluated this phenomenon in a novel spontaneous intrauterine growth-restricted (IUGR) model in Yucatan miniature pigs. METHODS: IUGR piglets (n = 6, 3 days old, 0.73 ± 0.11 kg) were paired with a normal weight (NW) same-sex littermate (n = 6, 1.11 ± 0.13 kg), fed milk replacer for 4 weeks followed by a standard diet ad libitum for 5 h/day. At 9 months of age, arterial blood pressure (BP) telemeters were implanted to assess BP before (0.5% NaCl) and after (4.5% NaCl) a 7-day salt-loading period. At 10 months of age, nephron numbers were determined. RESULTS: Prior to sexual maturity, IUGR pigs showed greater (p < 0.05) relative feed intake and experienced significant catch-up growth. Adult IUGR pigs also had higher BP (diastolic BP: 93.8 ± 5.5 vs. 90.0 ± 8.7 mm Hg, p < 0.05) and 43% fewer nephrons per kidney (p < 0.05). Nephron number was positively associated with birth weight and negatively correlated with BP (p < 0.05). Acute salt loading increased BP in both groups (p < 0.05); however, the degree of salt sensitivity was similar between groups (p > 0.05). CONCLUSIONS: In conclusion, IUGR piglets have reduced nephron endowment associated with a modest BP increase in early adulthood. This new model can be used to conduct longitudinal mechanistic studies on the early programming phenomenon.