Mouse hepatic lipase alleles with variable effects on lipoprotein composition and size[S]
The structural features responsible for the activities of hepatic lipase (HL) can be clarified by in vivo comparisons of naturally occurring variants. The coding sequence of HL from C57BL/6J (B6) and SPRET/EiJ (SPRET) mice differs by four amino acids (S106N, A156V, L416V, S480T); however, these chan...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2010-05-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520410594 |
| _version_ | 1828942299014365184 |
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| author | Serena M. Pratt Sally Chiu Glenda M. Espinal Noreene M. Shibata Howard Wong Craig H. Warden |
| author_facet | Serena M. Pratt Sally Chiu Glenda M. Espinal Noreene M. Shibata Howard Wong Craig H. Warden |
| author_sort | Serena M. Pratt |
| collection | DOAJ |
| description | The structural features responsible for the activities of hepatic lipase (HL) can be clarified by in vivo comparisons of naturally occurring variants. The coding sequence of HL from C57BL/6J (B6) and SPRET/EiJ (SPRET) mice differs by four amino acids (S106N, A156V, L416V, S480T); however, these changes are not predicted to influence HL function. To test for allelic effects, we generated SPRET-HL transgenics with physiological levels of HL mRNA and HL activity that was parallel in female transgenics and about 70% higher in male transgenics, toward tri-[3H]oleate, compared with B6 controls. We found no correlation between activity levels and plasma lipids. However, significant allelic effects on plasma lipids were observed. Compared with B6-HL, SPRET-HL mediated reductions in total cholesterol (TC) and VLDL-, LDL- and HDL-cholesterol and HDL-triglyceride (TG) in fed males, and SPRET-HL decreased total TG and VLDL- and HDL-TG levels in fasted males. Fasted female transgenics had reduced TC compared with controls. We also found allele and sex effects on lipoprotein particle size. Male transgenic mice had increased VLDL and decreased LDL size, and female transgenic mice had decreased HDL size compared with control animals. These findings demonstrate highly divergent effects of naturally occurring HL coding sequence variants on lipid and lipoprotein metabolism. |
| first_indexed | 2024-12-14T03:53:37Z |
| format | Article |
| id | doaj.art-1d88c81d41bd42e083da4be1266644d1 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-14T03:53:37Z |
| publishDate | 2010-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-1d88c81d41bd42e083da4be1266644d12022-12-21T23:18:09ZengElsevierJournal of Lipid Research0022-22752010-05-0151510351048Mouse hepatic lipase alleles with variable effects on lipoprotein composition and size[S]Serena M. Pratt0Sally Chiu1Glenda M. Espinal2Noreene M. Shibata3Howard Wong4Craig H. Warden5Section of Neurobiology, Physiology, Behavior, Department of Pediatrics, University of California, Davis, CAChildren's Hospital Oakland Research Institute, Oakland, CASection of Neurobiology, Physiology, Behavior, Department of Pediatrics, University of California, Davis, CASection of Neurobiology, Physiology, Behavior, Department of Pediatrics, University of California, Davis, CALipid Research Laboratory, Veterans Affairs Greater Los Angeles Healthcare System and Department of Medicine, University of California, Los Angeles, CATo whom correspondence should be addressed; Section of Neurobiology, Physiology, Behavior, Department of Pediatrics, University of California, Davis, CAThe structural features responsible for the activities of hepatic lipase (HL) can be clarified by in vivo comparisons of naturally occurring variants. The coding sequence of HL from C57BL/6J (B6) and SPRET/EiJ (SPRET) mice differs by four amino acids (S106N, A156V, L416V, S480T); however, these changes are not predicted to influence HL function. To test for allelic effects, we generated SPRET-HL transgenics with physiological levels of HL mRNA and HL activity that was parallel in female transgenics and about 70% higher in male transgenics, toward tri-[3H]oleate, compared with B6 controls. We found no correlation between activity levels and plasma lipids. However, significant allelic effects on plasma lipids were observed. Compared with B6-HL, SPRET-HL mediated reductions in total cholesterol (TC) and VLDL-, LDL- and HDL-cholesterol and HDL-triglyceride (TG) in fed males, and SPRET-HL decreased total TG and VLDL- and HDL-TG levels in fasted males. Fasted female transgenics had reduced TC compared with controls. We also found allele and sex effects on lipoprotein particle size. Male transgenic mice had increased VLDL and decreased LDL size, and female transgenic mice had decreased HDL size compared with control animals. These findings demonstrate highly divergent effects of naturally occurring HL coding sequence variants on lipid and lipoprotein metabolism.http://www.sciencedirect.com/science/article/pii/S0022227520410594129 donor alleleallelehepatic lipaselipoproteinnatural variantobesity |
| spellingShingle | Serena M. Pratt Sally Chiu Glenda M. Espinal Noreene M. Shibata Howard Wong Craig H. Warden Mouse hepatic lipase alleles with variable effects on lipoprotein composition and size[S] Journal of Lipid Research 129 donor allele allele hepatic lipase lipoprotein natural variant obesity |
| title | Mouse hepatic lipase alleles with variable effects on lipoprotein composition and size[S] |
| title_full | Mouse hepatic lipase alleles with variable effects on lipoprotein composition and size[S] |
| title_fullStr | Mouse hepatic lipase alleles with variable effects on lipoprotein composition and size[S] |
| title_full_unstemmed | Mouse hepatic lipase alleles with variable effects on lipoprotein composition and size[S] |
| title_short | Mouse hepatic lipase alleles with variable effects on lipoprotein composition and size[S] |
| title_sort | mouse hepatic lipase alleles with variable effects on lipoprotein composition and size s |
| topic | 129 donor allele allele hepatic lipase lipoprotein natural variant obesity |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520410594 |
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