Genetically Diverse Pig Models in Nutrition Research Related to Lipoprotein and Cholesterol Metabolism

Mersmann, Harry J.

doi:10.1007/978-1-4615-5885-9_36

Cited by 7 publications

(7 citation statements)

References 63 publications

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“…Previous studies have focused on the regulation of HMGCR hepatic activity by dietary fat indicating that this enzyme is particularly inhibited by dietary cholesterol reductase activity in young pigs (McWhinney et al, 1996;Pond and Mersmann, 1996) and that the modulation of hepatic reductase activity is related, at least in guinea pigs, to the ratio of saturation to insaturation of the dietary fat (Fernandez and McNamara, 1991). Regarding the porcine HMGCR gene, restriction fragment length polymorphism (RFLP) polymorphisms in the porcine gene have been previously described by Southern blotting (Davis et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…Its sequence and promoter transactivation has also been characterised in model animals such as rat (Osborne et al, 2004), mouse -E-mail: romi.pena@irta.cat (Datta et al, 2006) and opossum (Chan et al, 2008) with a view to studying the genetics of serum cholesterol and TG variation and their consequences over atherosclerosis. The pig has also been used as a model for atherogenesis, obesity and lipoprotein and cholesterol metabolism due to anatomic and pathogenic similarities with humans (reviewed in Pond and Mersmann, 1996). HMGCR activity is regulated at both post-transcriptional and post-translational levels.…”

Section: Introductionmentioning

confidence: 99%

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Functional and association studies on the pig HMGCR gene, a cholesterol-synthesis limiting enzyme

Cánovas

Quintanilla

Gallardo

et al. 2010

Animal

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The 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is the rate-limiting enzyme in the biosynthesis of cholesterol. We have studied the role of theHMGCRgene in pig lipid metabolism by means of expression and structural analysis. We describe here the complete coding region of this gene in pigs and report two synonymous single nucleotide polymorphisms in the coding region. We have, additionally, studied the association of one of these polymorphisms (HMGCR:c.807A>C) with several lipid deposition- and cholesterol-related traits in a half-sib population generated from a commercial Duroc line, showing in some families a positive relationship ofHMGCR:c.807Aallele with serum low-density lipoprotein (LDL)-bound cholesterol and triglyceride levels, and also with intramuscular fat (IMF) content ofgluteus mediusmuscle. We have also assessed the expression levels in muscle and in liver from 68 Duroc individuals corresponding to the most extreme animals for the analysed traits. LiverHMGCRexpression correlated negatively with the serum high-density lipoprotein (HDL) levels, carcass lean percentage and stearic acid content, while muscle expression correlated also negatively with the carcass lean percentage, stearic and linoleic acids content, but showed a positive correlation with the serum lipid cholesterol (HDL, LDL and total cholesterol), IMF and muscle oleic and palmitic fatty acid content. With this information, we have performed an association analysis of expression data with lipid metabolism phenotypic levels and theHMGCRgenotype. The results indicate thatHMGCRexpression levels in muscle are different in the two groups of pigs with extreme values for fat deposition and total cholesterol levels, and also between animals with the differentHMGCRgenotypes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Functional and association studies on the pig HMGCR gene, a cholesterol-synthesis limiting enzyme

Cánovas

Quintanilla

Gallardo

et al. 2010

Animal

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“…Piglets are used as models for VA metabolism (15) because of their similar size, gastrointestinal physiology (16,17), and lipoprotein and cholesterol metabolism (18). Therefore, a newborn piglet study was undertaken to simulate the conditions of neonates receiving graded VA doses.…”

Section: Introductionmentioning

confidence: 99%

Single High-Dose Vitamin A Supplementation to Neonatal Piglets Results in a Transient Dose Response in Extrahepatic Organs and Sustained Increases in Liver Stores

Gannon

Davis

Nair

et al. 2017

The Journal of Nutrition

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Neonatal vitamin A (VA) supplementation is being evaluated as a public health policy for preventing infant mortality, but inconsistencies in mortality trials demand mechanistic work to determine biological plausibility. We investigated the absorption, distribution, and storage of single large oral VA doses administered shortly after birth. Fifty pregnant sows () were fed a VA-free diet. Male and female newborn piglets ( = 313) were orally administered 0, 25,000, 50,000, or 200,000 IU VA in oil within 12 h of birth when mean ± SD weight was 1.56 ± 0.25 kg. Blood was drawn to determine absorption and storage 0.5-240 h after administration. Metabolic and postnatal dose-timing substudies were performed. Liver, lung, kidney, spleen, and adrenal VA concentrations were determined 7-240 h after administration. Serum retinol and retinyl ester concentrations responded to treatment ( < 0.0001); however, differences between groups disappeared by 96 h. Liver VA concentrations responded to treatment ( < 0.0001), which persisted for 240 h. Liver VA for control piglets at 10 d (mean ± SD: 0.05 ± 0.02 μmol/g) was ≤0.1 μmol/g (deficiency), whereas groups that received VA maintained concentrations >0.1 μmol/g. Extrahepatic tissue VA concentrations displayed treatment effects ( ≤ 0.0077); groups that received treatments had higher VA concentrations than controls at early time points. Lung, kidney, and spleen VA did not differ between groups by 96 h, whereas adrenal glands did not differ by 240 h. Body weight was affected by treatment ( = 0.0002); VA-deficient piglets weighed 23-29% more than all treated groups 240 h after administration. A high dose of VA administered to newborn piglets was well absorbed, appeared in serum primarily as retinyl esters, and was taken up dose-dependently in all tissues studied; however, enhancement did not persist in sera, lungs, kidneys, spleens, or adrenal glands. Short-term impacts of retinoid signaling on weight gain remain to be elucidated, and longer follow-up studies are needed.

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“…Against such a background, we planned to produce human apo(a) transgenic NIBS miniature pigs. Pigs have been used as an animal model for human cholesterol-related disease states for many decades [ 27 ], and it has been reported that the lipoprotein pattern of pig serum is similar in many ways to that of human serum [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Many aspects of cholesterol and lipoprotein metabolism in pigs and their responses to dietary cholesterol and fat resemble those of humans. One of the most favorable characteristics of pigs is that they are omnivorous animals [ 27 ]. The purpose of this study was to produce a human apo(a) transgenic Nippon Institute for Biological Science (NIBS) miniature pig that could be used to study atherosclerosis by somatic cell nuclear transfer (SCNT).…”

Section: Introductionmentioning

confidence: 99%

Production of human apolipoprotein(a) transgenic NIBS miniature pigs by somatic cell nuclear transfer

et al. 2016

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Most cases of ischemic heart disease and stroke occur as a result of atherosclerosis. The purpose of this study was to produce a new Nippon Institute for Biological Science (NIBS) miniature pig model by somatic cell nuclear transfer (SCNT) for studying atherosclerosis. The human apolipoprotein(a) (apo(a)) genes were transfected into kidney epithelial cells derived from a male and a female piglet. Male cells were used as donors initially, and 275 embryos were transferred to surrogates. Three offspring were delivered, and the production efficiency was 1.1% (3/275). Serial female cells were injected into 937 enucleated oocytes. Eight offspring were delivered (production efficiency: 0.9%) from surrogates. One male and 2 female transgenic miniature pigs matured well. Lipoprotein(a) was found in the male and one of the female transgenic animals. These results demonstrate successful production of human apo(a) transgenic NIBS miniature pigs by SCNT. Our goal is to establish a human apo(a) transgenic NIBS miniature pig colony for studying atherosclerosis.

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Genetically Diverse Pig Models in Nutrition Research Related to Lipoprotein and Cholesterol Metabolism

Cited by 7 publications

References 63 publications

Functional and association studies on the pig HMGCR gene, a cholesterol-synthesis limiting enzyme

Functional and association studies on the pig HMGCR gene, a cholesterol-synthesis limiting enzyme

Single High-Dose Vitamin A Supplementation to Neonatal Piglets Results in a Transient Dose Response in Extrahepatic Organs and Sustained Increases in Liver Stores

Production of human apolipoprotein(a) transgenic NIBS miniature pigs by somatic cell nuclear transfer

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