First international descriptive and interventional survey for cholesterol and non-cholesterol sterol determination by gas- and liquid- chromatography–Urgent need for harmonisation of analytical methods

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

Developmental origins of cardiovascular disease in Yucatan miniature swine

Epidemiological studies have consistently indicated that low birth weight is associated with increased risks of chronic diseases in adulthood. Due to limitations of human studies, various animal models are used to elucidate the mechanisms regulating developmental programming of chronic adult diseases. A large proportion (80-90%) of the human incidence of intrauterine growth restriction, resulting in low birth weight, is may be due to impaired nutrient perfusion through the placenta. Spontaneous low birth weight animal models also represent placental insufficiency and may be appropriate models for the human. The overall objective of this thesis was to determine whether the spontaneous naturally occurring low birth weight (i.e., runt) Yucatan miniature pig represents a suitable model for studying developmental origins of chronic adult diseases by investigating biological markers of obesity and cardiovascular diseases. The runts showed qualities similar to low birth weight infants, i.e., small size at birth, an increased rate of postnatal growth (catch-up growth), and organ and metabolic changes which led to the development of obesity and early indicators of cardiovascular diseases. Specifically, runts experienced catch-up growth (prior to sexual maturity at 7 mo old). The catch-up growth was partly due to increased feed intake, which was independent of the post-weaning diet provided, suggesting developmental programming of food intake regulation. Catch-up growth was also associated with increased adiposity in the runts. Furthermore, blood pressure was inversely related to birth weight, similar to findings in epidemiological studies. The higher blood pressure in the runts was significantly correlated to lower nephron number. The results showed that low birth weight was associated with a dyslipidaemic plasma profile as indicated by the higher plasma triglyceride levels in the runts in both the fasted and postprandial states. Finally, a post-weaning dietary intake also plays an important role as a determinant of chronic disease outcomes; a post-weaning Western-style diet that was high in salt, fat and sugar exacerbate early programming of blood pressure and lipid profile in the runts. Overall, the Yucatan miniature swine has many attributes for a good animal model to explore mechanisms that contribute to the developmental origins of human adult chronic diseases

Effects of a Diet High in Salt, Fat, and Sugar on Telemetric Blood Pressure Measurements in Conscious, Unrestrained Adult Yucatan Miniature Swine (Sus scrofa)

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)

Intrauterine growth-restricted Yucatan miniature pigs experience early catch-up growth leading to greater adiposity and impaired lipid metabolism as young adults

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 d old, 0.73 Âą 0.04 kg) were paired with normal weight (NW) same-sex littermates (n = 6, 1.11 Âą 0.05 kg) and fed milk replacer ad libitum for 4 wk. Thereafter, all pigs were fed a standard diet ad libitum for 5 h/d with growth, intakes and blood samples collected for 8 mo. At 9 mo old, pigs were surgically fitted with venous catheters and an oral fat tolerance test was performed. At 10 mo 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 (PThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Progress and perspectives in plant sterol and plant stanol research.

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

Progress and perspectives in plant sterol and plant stanol research

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