PPARα activation increases triglyceride mass and adipose differentiation-related protein in hepatocytes
Adipose differentiation-related protein (ADRP) is a lipid droplet-associated protein that is expressed in various tissues. In mice treated with the peroxisome proliferator-activated receptor α (PPARα) agonist Wy14,643 (Wy), hepatic mRNA and protein levels of ADRP as well as hepatic triglyceride cont...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2006-02-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520336336 |
| _version_ | 1818385194219995136 |
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| author | Ulrika Edvardsson Anna Ljungberg Daniel Lindén Lena William-Olsson Helena Peilot-Sjögren Andrea Ahnmark Jan Oscarsson |
| author_facet | Ulrika Edvardsson Anna Ljungberg Daniel Lindén Lena William-Olsson Helena Peilot-Sjögren Andrea Ahnmark Jan Oscarsson |
| author_sort | Ulrika Edvardsson |
| collection | DOAJ |
| description | Adipose differentiation-related protein (ADRP) is a lipid droplet-associated protein that is expressed in various tissues. In mice treated with the peroxisome proliferator-activated receptor α (PPARα) agonist Wy14,643 (Wy), hepatic mRNA and protein levels of ADRP as well as hepatic triglyceride content increased. Also in primary mouse hepatocytes, Wy increased ADRP expression and intracellular triglyceride mass. The triglyceride mass increased in spite of unchanged triglyceride biosynthesis and increased palmitic acid oxidation. However, Wy incubation decreased the secretion of newly synthesized triglycerides, whereas apolipoprotein B secretion increased. Thus, decreased availability of triglycerides for VLDL assembly could help to explain the cellular accumulation of triglycerides after Wy treatment. We hypothesized that this effect could be mediated by increased ADRP expression. Similar to PPARα activation, adenovirus-mediated ADRP overexpression in mouse hepatocytes enhanced cellular triglyceride mass and decreased the secretion of newly synthesized triglycerides. In ADRP-overexpressing cells, Wy incubation resulted in a further decrease in triglyceride secretion. This effect of Wy was not attributable to decreased cellular triglycerides after increased fatty acid oxidation because the triglyceride mass in Wy-treated ADRP-overexpressing cells was unchanged. In summary, PPARα activation prevents the availability of triglycerides for VLDL assembly and increases hepatic triglyceride content in part by increasing the expression of ADRP. |
| first_indexed | 2024-12-14T03:34:17Z |
| format | Article |
| id | doaj.art-bcacd8980c8f479d9b4c9994bf2cf849 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-14T03:34:17Z |
| publishDate | 2006-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-bcacd8980c8f479d9b4c9994bf2cf8492022-12-21T23:18:40ZengElsevierJournal of Lipid Research0022-22752006-02-01472329340PPARα activation increases triglyceride mass and adipose differentiation-related protein in hepatocytesUlrika Edvardsson0Anna Ljungberg1Daniel Lindén2Lena William-Olsson3Helena Peilot-Sjögren4Andrea Ahnmark5Jan Oscarsson6Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden; Department of Physiology, Sahlgrenska University Hospital, Göteborg, Sweden; AstraZeneca Research and Development, Mölndal, SwedenWallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden; Department of Physiology, Sahlgrenska University Hospital, Göteborg, Sweden; AstraZeneca Research and Development, Mölndal, SwedenWallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden; Department of Physiology, Sahlgrenska University Hospital, Göteborg, Sweden; AstraZeneca Research and Development, Mölndal, SwedenWallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden; Department of Physiology, Sahlgrenska University Hospital, Göteborg, Sweden; AstraZeneca Research and Development, Mölndal, SwedenWallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden; Department of Physiology, Sahlgrenska University Hospital, Göteborg, Sweden; AstraZeneca Research and Development, Mölndal, SwedenWallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden; Department of Physiology, Sahlgrenska University Hospital, Göteborg, Sweden; AstraZeneca Research and Development, Mölndal, SwedenWallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden; Department of Physiology, Sahlgrenska University Hospital, Göteborg, Sweden; AstraZeneca Research and Development, Mölndal, SwedenAdipose differentiation-related protein (ADRP) is a lipid droplet-associated protein that is expressed in various tissues. In mice treated with the peroxisome proliferator-activated receptor α (PPARα) agonist Wy14,643 (Wy), hepatic mRNA and protein levels of ADRP as well as hepatic triglyceride content increased. Also in primary mouse hepatocytes, Wy increased ADRP expression and intracellular triglyceride mass. The triglyceride mass increased in spite of unchanged triglyceride biosynthesis and increased palmitic acid oxidation. However, Wy incubation decreased the secretion of newly synthesized triglycerides, whereas apolipoprotein B secretion increased. Thus, decreased availability of triglycerides for VLDL assembly could help to explain the cellular accumulation of triglycerides after Wy treatment. We hypothesized that this effect could be mediated by increased ADRP expression. Similar to PPARα activation, adenovirus-mediated ADRP overexpression in mouse hepatocytes enhanced cellular triglyceride mass and decreased the secretion of newly synthesized triglycerides. In ADRP-overexpressing cells, Wy incubation resulted in a further decrease in triglyceride secretion. This effect of Wy was not attributable to decreased cellular triglycerides after increased fatty acid oxidation because the triglyceride mass in Wy-treated ADRP-overexpressing cells was unchanged. In summary, PPARα activation prevents the availability of triglycerides for VLDL assembly and increases hepatic triglyceride content in part by increasing the expression of ADRP.http://www.sciencedirect.com/science/article/pii/S0022227520336336Wy14,643primary hepatocytestriglyceride synthesisfatty acid oxidationtriglyceride secretionapolipoprotein B-100 |
| spellingShingle | Ulrika Edvardsson Anna Ljungberg Daniel Lindén Lena William-Olsson Helena Peilot-Sjögren Andrea Ahnmark Jan Oscarsson PPARα activation increases triglyceride mass and adipose differentiation-related protein in hepatocytes Journal of Lipid Research Wy14,643 primary hepatocytes triglyceride synthesis fatty acid oxidation triglyceride secretion apolipoprotein B-100 |
| title | PPARα activation increases triglyceride mass and adipose differentiation-related protein in hepatocytes |
| title_full | PPARα activation increases triglyceride mass and adipose differentiation-related protein in hepatocytes |
| title_fullStr | PPARα activation increases triglyceride mass and adipose differentiation-related protein in hepatocytes |
| title_full_unstemmed | PPARα activation increases triglyceride mass and adipose differentiation-related protein in hepatocytes |
| title_short | PPARα activation increases triglyceride mass and adipose differentiation-related protein in hepatocytes |
| title_sort | pparα activation increases triglyceride mass and adipose differentiation related protein in hepatocytes |
| topic | Wy14,643 primary hepatocytes triglyceride synthesis fatty acid oxidation triglyceride secretion apolipoprotein B-100 |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520336336 |
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