Changes in soluble LDL receptor and lipoprotein fractions in response to diet in the DIETFITS weight loss study
Circulating levels of the soluble ligand-binding ectodomain of the LDL receptor (sLDLR) that is proteolytically cleaved from the cell surface have been shown to correlate with plasma triglycerides, but the lipid and lipoprotein effects of longitudinal changes in sLDLR have not been examined. We soug...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-03-01
|
| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227524000087 |
| _version_ | 1797238122944135168 |
|---|---|
| author | Ronald M. Krauss Lois M. Fisher Sarah M. King Christopher D. Gardner |
| author_facet | Ronald M. Krauss Lois M. Fisher Sarah M. King Christopher D. Gardner |
| author_sort | Ronald M. Krauss |
| collection | DOAJ |
| description | Circulating levels of the soluble ligand-binding ectodomain of the LDL receptor (sLDLR) that is proteolytically cleaved from the cell surface have been shown to correlate with plasma triglycerides, but the lipid and lipoprotein effects of longitudinal changes in sLDLR have not been examined. We sought to assess associations between changes in sLDLR and detailed lipoprotein measurements between baseline and 6 months in participants in the DIETFITS (Diet Intervention Examining The Factors Interacting with Treatment Success) weight loss trial who were randomly assigned to the low-fat (n = 225) or low-carbohydrate (n = 236) diet arms. sLDLR was assayed using a proteomic procedure, lipids and apoprotein (apo) B and apoAI were measured by standard assays, and lipoprotein particle subfractions were quantified by ion mobility methodology. Changes in sLDLR were significantly positively associated with changes in plasma cholesterol, triglycerides, apoB, large-sized and medium-sized VLDL, and small and very small LDL, and inversely with changes in large LDL and HDL. The lipoprotein subfraction associations with sLDLR were independent of age, sex, diet, and BMI, but all except for large LDL were reduced to insignificance when adjusted for triglyceride change. Principal component analysis identified three independent clusters of changes in lipoprotein subfractions that accounted for 78% of their total variance. Change in sLDLR was most strongly correlated with change in the principal component that was loaded positively with large VLDL and small and very small LDL and negatively with large LDL and HDL. In conclusion, sLDLR is a component of a cluster of lipids and lipoproteins that are characteristic of atherogenic dyslipidemia. |
| first_indexed | 2024-03-08T00:02:13Z |
| format | Article |
| id | doaj.art-92b257945f17432b8df1888750aa38bd |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-04-24T17:30:38Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-92b257945f17432b8df1888750aa38bd2024-03-28T06:36:38ZengElsevierJournal of Lipid Research0022-22752024-03-01653100503Changes in soluble LDL receptor and lipoprotein fractions in response to diet in the DIETFITS weight loss studyRonald M. Krauss0Lois M. Fisher1Sarah M. King2Christopher D. Gardner3Departments of Pediatrics and Medicine, University of California, San Francisco, San Francisco, CA, USA; For correspondence: Ronald M. KraussDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USADepartment of Pediatrics, University of California, San Francisco, San Francisco, CA, USAStanford Prevention Research Center, Department of Medicine, Stanford University Medical School, Stanford, CA, USACirculating levels of the soluble ligand-binding ectodomain of the LDL receptor (sLDLR) that is proteolytically cleaved from the cell surface have been shown to correlate with plasma triglycerides, but the lipid and lipoprotein effects of longitudinal changes in sLDLR have not been examined. We sought to assess associations between changes in sLDLR and detailed lipoprotein measurements between baseline and 6 months in participants in the DIETFITS (Diet Intervention Examining The Factors Interacting with Treatment Success) weight loss trial who were randomly assigned to the low-fat (n = 225) or low-carbohydrate (n = 236) diet arms. sLDLR was assayed using a proteomic procedure, lipids and apoprotein (apo) B and apoAI were measured by standard assays, and lipoprotein particle subfractions were quantified by ion mobility methodology. Changes in sLDLR were significantly positively associated with changes in plasma cholesterol, triglycerides, apoB, large-sized and medium-sized VLDL, and small and very small LDL, and inversely with changes in large LDL and HDL. The lipoprotein subfraction associations with sLDLR were independent of age, sex, diet, and BMI, but all except for large LDL were reduced to insignificance when adjusted for triglyceride change. Principal component analysis identified three independent clusters of changes in lipoprotein subfractions that accounted for 78% of their total variance. Change in sLDLR was most strongly correlated with change in the principal component that was loaded positively with large VLDL and small and very small LDL and negatively with large LDL and HDL. In conclusion, sLDLR is a component of a cluster of lipids and lipoproteins that are characteristic of atherogenic dyslipidemia.http://www.sciencedirect.com/science/article/pii/S0022227524000087triglycerideVLDLLDLlipoproteins/metabolismcholesterolnutrition |
| spellingShingle | Ronald M. Krauss Lois M. Fisher Sarah M. King Christopher D. Gardner Changes in soluble LDL receptor and lipoprotein fractions in response to diet in the DIETFITS weight loss study Journal of Lipid Research triglyceride VLDL LDL lipoproteins/metabolism cholesterol nutrition |
| title | Changes in soluble LDL receptor and lipoprotein fractions in response to diet in the DIETFITS weight loss study |
| title_full | Changes in soluble LDL receptor and lipoprotein fractions in response to diet in the DIETFITS weight loss study |
| title_fullStr | Changes in soluble LDL receptor and lipoprotein fractions in response to diet in the DIETFITS weight loss study |
| title_full_unstemmed | Changes in soluble LDL receptor and lipoprotein fractions in response to diet in the DIETFITS weight loss study |
| title_short | Changes in soluble LDL receptor and lipoprotein fractions in response to diet in the DIETFITS weight loss study |
| title_sort | changes in soluble ldl receptor and lipoprotein fractions in response to diet in the dietfits weight loss study |
| topic | triglyceride VLDL LDL lipoproteins/metabolism cholesterol nutrition |
| url | http://www.sciencedirect.com/science/article/pii/S0022227524000087 |
| work_keys_str_mv | AT ronaldmkrauss changesinsolubleldlreceptorandlipoproteinfractionsinresponsetodietinthedietfitsweightlossstudy AT loismfisher changesinsolubleldlreceptorandlipoproteinfractionsinresponsetodietinthedietfitsweightlossstudy AT sarahmking changesinsolubleldlreceptorandlipoproteinfractionsinresponsetodietinthedietfitsweightlossstudy AT christopherdgardner changesinsolubleldlreceptorandlipoproteinfractionsinresponsetodietinthedietfitsweightlossstudy |