Lipid phosphate phosphatase 3 regulates adipocyte sphingolipid synthesis, but not developmental adipogenesis or diet-induced obesity in mice.
Dephosphorylation of phosphatidic acid (PA) is the penultimate step in triglyceride synthesis. Adipocytes express soluble intracellular PA-specific phosphatases (Lipins) and broader specificity membrane-associated lipid phosphate phosphatases (LPPs) that can also dephosphorylate PA. Inactivation of...
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| _version_ | 1850076700397797376 |
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| author | Lorenzo Federico Liping Yang Jason Brandon Manikandan Panchatcharam Hongmei Ren Paul Mueller Manjula Sunkara Diana Escalante-Alcalde Andrew J Morris Susan S Smyth |
| author_facet | Lorenzo Federico Liping Yang Jason Brandon Manikandan Panchatcharam Hongmei Ren Paul Mueller Manjula Sunkara Diana Escalante-Alcalde Andrew J Morris Susan S Smyth |
| author_sort | Lorenzo Federico |
| collection | DOAJ |
| description | Dephosphorylation of phosphatidic acid (PA) is the penultimate step in triglyceride synthesis. Adipocytes express soluble intracellular PA-specific phosphatases (Lipins) and broader specificity membrane-associated lipid phosphate phosphatases (LPPs) that can also dephosphorylate PA. Inactivation of lipin1 causes lipodystrophy in mice due to defective developmental adipogenesis. Triglyceride synthesis is diminished but not ablated by inactivation of lipin1 in differentiated adipocytes implicating other PA phosphatases in this process. To investigate the possible role of LPPs in adipocyte lipid metabolism and signaling we made mice with adipocyte-targeted inactivation of LPP3 encoded by the Plpp3(Ppap2b) gene. Adipocyte LPP3 deficiency resulted in blunted ceramide and sphingomyelin accumulation during diet-induced adipose tissue expansion, accumulation of the LPP3 substrate sphingosine 1- phosphate, and reduced expression of serine palmitoyl transferase. However, adiposity was unaffected by LPP3 deficiency on standard, high fat diet or Western diets, although Western diet-fed mice with adipocyte LPP3 deficiency exhibited improved glucose tolerance. Our results demonstrate functional compartmentalization of lipid phosphatase activity in adipocytes and identify an unexpected role for LPP3 in the regulation of diet-dependent sphingolipid synthesis that may impact on insulin signaling. |
| format | Article |
| id | doaj-art-fa2d1a3ec0ce47cd915a9caa09a58746 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-fa2d1a3ec0ce47cd915a9caa09a587462025-08-20T02:45:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019806310.1371/journal.pone.0198063Lipid phosphate phosphatase 3 regulates adipocyte sphingolipid synthesis, but not developmental adipogenesis or diet-induced obesity in mice.Lorenzo FedericoLiping YangJason BrandonManikandan PanchatcharamHongmei RenPaul MuellerManjula SunkaraDiana Escalante-AlcaldeAndrew J MorrisSusan S SmythDephosphorylation of phosphatidic acid (PA) is the penultimate step in triglyceride synthesis. Adipocytes express soluble intracellular PA-specific phosphatases (Lipins) and broader specificity membrane-associated lipid phosphate phosphatases (LPPs) that can also dephosphorylate PA. Inactivation of lipin1 causes lipodystrophy in mice due to defective developmental adipogenesis. Triglyceride synthesis is diminished but not ablated by inactivation of lipin1 in differentiated adipocytes implicating other PA phosphatases in this process. To investigate the possible role of LPPs in adipocyte lipid metabolism and signaling we made mice with adipocyte-targeted inactivation of LPP3 encoded by the Plpp3(Ppap2b) gene. Adipocyte LPP3 deficiency resulted in blunted ceramide and sphingomyelin accumulation during diet-induced adipose tissue expansion, accumulation of the LPP3 substrate sphingosine 1- phosphate, and reduced expression of serine palmitoyl transferase. However, adiposity was unaffected by LPP3 deficiency on standard, high fat diet or Western diets, although Western diet-fed mice with adipocyte LPP3 deficiency exhibited improved glucose tolerance. Our results demonstrate functional compartmentalization of lipid phosphatase activity in adipocytes and identify an unexpected role for LPP3 in the regulation of diet-dependent sphingolipid synthesis that may impact on insulin signaling.https://storage.googleapis.com/plos-corpus-prod/10.1371/journal.pone.0198063/1/pone.0198063.pdf?X-Goog-Algorithm=GOOG4-RSA-SHA256&X-Goog-Credential=wombat-sa%40plos-prod.iam.gserviceaccount.com%2F20210218%2Fauto%2Fstorage%2Fgoog4_request&X-Goog-Date=20210218T134758Z&X-Goog-Expires=3600&X-Goog-SignedHeaders=host&X-Goog-Signature=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 |
| spellingShingle | Lorenzo Federico Liping Yang Jason Brandon Manikandan Panchatcharam Hongmei Ren Paul Mueller Manjula Sunkara Diana Escalante-Alcalde Andrew J Morris Susan S Smyth Lipid phosphate phosphatase 3 regulates adipocyte sphingolipid synthesis, but not developmental adipogenesis or diet-induced obesity in mice. PLoS ONE |
| title | Lipid phosphate phosphatase 3 regulates adipocyte sphingolipid synthesis, but not developmental adipogenesis or diet-induced obesity in mice. |
| title_full | Lipid phosphate phosphatase 3 regulates adipocyte sphingolipid synthesis, but not developmental adipogenesis or diet-induced obesity in mice. |
| title_fullStr | Lipid phosphate phosphatase 3 regulates adipocyte sphingolipid synthesis, but not developmental adipogenesis or diet-induced obesity in mice. |
| title_full_unstemmed | Lipid phosphate phosphatase 3 regulates adipocyte sphingolipid synthesis, but not developmental adipogenesis or diet-induced obesity in mice. |
| title_short | Lipid phosphate phosphatase 3 regulates adipocyte sphingolipid synthesis, but not developmental adipogenesis or diet-induced obesity in mice. |
| title_sort | lipid phosphate phosphatase 3 regulates adipocyte sphingolipid synthesis but not developmental adipogenesis or diet induced obesity in mice |
| url | https://storage.googleapis.com/plos-corpus-prod/10.1371/journal.pone.0198063/1/pone.0198063.pdf?X-Goog-Algorithm=GOOG4-RSA-SHA256&X-Goog-Credential=wombat-sa%40plos-prod.iam.gserviceaccount.com%2F20210218%2Fauto%2Fstorage%2Fgoog4_request&X-Goog-Date=20210218T134758Z&X-Goog-Expires=3600&X-Goog-SignedHeaders=host&X-Goog-Signature=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 |
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