Role of LRP1 and ERK and cAMP Signaling Pathways in Lactoferrin-Induced Lipolysis in Mature Rat Adipocytes.
Lactoferrin (LF) is a multifunctional glycoprotein present in milk. A clinical study showed that enteric-coated bovine LF tablets decrease visceral fat accumulation. Furthermore, animal studies revealed that ingested LF is partially delivered to mesenteric fat, and in vitro studies showed that LF pr...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4623961?pdf=render |
| _version_ | 1818508568953880576 |
|---|---|
| author | Keiko Ikoma-Seki Kanae Nakamura Satoru Morishita Tomoji Ono Keikichi Sugiyama Hoyoku Nishino Hisashi Hirano Michiaki Murakoshi |
| author_facet | Keiko Ikoma-Seki Kanae Nakamura Satoru Morishita Tomoji Ono Keikichi Sugiyama Hoyoku Nishino Hisashi Hirano Michiaki Murakoshi |
| author_sort | Keiko Ikoma-Seki |
| collection | DOAJ |
| description | Lactoferrin (LF) is a multifunctional glycoprotein present in milk. A clinical study showed that enteric-coated bovine LF tablets decrease visceral fat accumulation. Furthermore, animal studies revealed that ingested LF is partially delivered to mesenteric fat, and in vitro studies showed that LF promotes lipolysis in mature adipocytes. The aim of the present study was to determine the mechanism underlying the induction of lipolysis in mature adipocytes that is induced by LF. To address this question, we used proteomics techniques to analyze protein expression profiles. Mature adipocytes from primary cultures of rat mesenteric fat were collected at various times after exposure to LF. Proteomic analysis revealed that the expression levels of hormone-sensitive lipase (HSL), which catalyzes the rate-limiting step of lipolysis, were upregulated and that HSL was activated by protein kinase A within 15 min after the cells were treated with LF. We previously reported that LF increases the intracellular concentration of cyclic adenosine monophosphate (cAMP), suggesting that LF activates the cAMP signaling pathway. In this study, we show that the expression level and the activity of the components of the extracellular signal-regulated kinase (ERK) signaling pathway were upregulated. Moreover, LF increased the activity of the transcription factor cAMP response element binding protein (CREB), which acts downstream in the cAMP and ERK signaling pathways and regulates the expression levels of adenylyl cyclase and HSL. Moreover, silencing of the putative LF receptor low-density lipoprotein receptor-related protein 1 (LRP1) attenuated lipolysis in LF-treated adipocytes. These results suggest that LF promoted lipolysis in mature adipocytes by regulating the expression levels of proteins involved in lipolysis through controlling the activity of cAMP/ERK signaling pathways via LRP1. |
| first_indexed | 2024-12-10T22:33:49Z |
| format | Article |
| id | doaj.art-e723fa076e604ed9b195329b78cae4b4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T22:33:49Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e723fa076e604ed9b195329b78cae4b42022-12-22T01:31:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011010e014137810.1371/journal.pone.0141378Role of LRP1 and ERK and cAMP Signaling Pathways in Lactoferrin-Induced Lipolysis in Mature Rat Adipocytes.Keiko Ikoma-SekiKanae NakamuraSatoru MorishitaTomoji OnoKeikichi SugiyamaHoyoku NishinoHisashi HiranoMichiaki MurakoshiLactoferrin (LF) is a multifunctional glycoprotein present in milk. A clinical study showed that enteric-coated bovine LF tablets decrease visceral fat accumulation. Furthermore, animal studies revealed that ingested LF is partially delivered to mesenteric fat, and in vitro studies showed that LF promotes lipolysis in mature adipocytes. The aim of the present study was to determine the mechanism underlying the induction of lipolysis in mature adipocytes that is induced by LF. To address this question, we used proteomics techniques to analyze protein expression profiles. Mature adipocytes from primary cultures of rat mesenteric fat were collected at various times after exposure to LF. Proteomic analysis revealed that the expression levels of hormone-sensitive lipase (HSL), which catalyzes the rate-limiting step of lipolysis, were upregulated and that HSL was activated by protein kinase A within 15 min after the cells were treated with LF. We previously reported that LF increases the intracellular concentration of cyclic adenosine monophosphate (cAMP), suggesting that LF activates the cAMP signaling pathway. In this study, we show that the expression level and the activity of the components of the extracellular signal-regulated kinase (ERK) signaling pathway were upregulated. Moreover, LF increased the activity of the transcription factor cAMP response element binding protein (CREB), which acts downstream in the cAMP and ERK signaling pathways and regulates the expression levels of adenylyl cyclase and HSL. Moreover, silencing of the putative LF receptor low-density lipoprotein receptor-related protein 1 (LRP1) attenuated lipolysis in LF-treated adipocytes. These results suggest that LF promoted lipolysis in mature adipocytes by regulating the expression levels of proteins involved in lipolysis through controlling the activity of cAMP/ERK signaling pathways via LRP1.http://europepmc.org/articles/PMC4623961?pdf=render |
| spellingShingle | Keiko Ikoma-Seki Kanae Nakamura Satoru Morishita Tomoji Ono Keikichi Sugiyama Hoyoku Nishino Hisashi Hirano Michiaki Murakoshi Role of LRP1 and ERK and cAMP Signaling Pathways in Lactoferrin-Induced Lipolysis in Mature Rat Adipocytes. PLoS ONE |
| title | Role of LRP1 and ERK and cAMP Signaling Pathways in Lactoferrin-Induced Lipolysis in Mature Rat Adipocytes. |
| title_full | Role of LRP1 and ERK and cAMP Signaling Pathways in Lactoferrin-Induced Lipolysis in Mature Rat Adipocytes. |
| title_fullStr | Role of LRP1 and ERK and cAMP Signaling Pathways in Lactoferrin-Induced Lipolysis in Mature Rat Adipocytes. |
| title_full_unstemmed | Role of LRP1 and ERK and cAMP Signaling Pathways in Lactoferrin-Induced Lipolysis in Mature Rat Adipocytes. |
| title_short | Role of LRP1 and ERK and cAMP Signaling Pathways in Lactoferrin-Induced Lipolysis in Mature Rat Adipocytes. |
| title_sort | role of lrp1 and erk and camp signaling pathways in lactoferrin induced lipolysis in mature rat adipocytes |
| url | http://europepmc.org/articles/PMC4623961?pdf=render |
| work_keys_str_mv | AT keikoikomaseki roleoflrp1anderkandcampsignalingpathwaysinlactoferrininducedlipolysisinmatureratadipocytes AT kanaenakamura roleoflrp1anderkandcampsignalingpathwaysinlactoferrininducedlipolysisinmatureratadipocytes AT satorumorishita roleoflrp1anderkandcampsignalingpathwaysinlactoferrininducedlipolysisinmatureratadipocytes AT tomojiono roleoflrp1anderkandcampsignalingpathwaysinlactoferrininducedlipolysisinmatureratadipocytes AT keikichisugiyama roleoflrp1anderkandcampsignalingpathwaysinlactoferrininducedlipolysisinmatureratadipocytes AT hoyokunishino roleoflrp1anderkandcampsignalingpathwaysinlactoferrininducedlipolysisinmatureratadipocytes AT hisashihirano roleoflrp1anderkandcampsignalingpathwaysinlactoferrininducedlipolysisinmatureratadipocytes AT michiakimurakoshi roleoflrp1anderkandcampsignalingpathwaysinlactoferrininducedlipolysisinmatureratadipocytes |