Oncostatin M Induces Lipolysis and Suppresses Insulin Response in 3T3-L1 Adipocytes
Oncostatin M (OSM) is an immune cell-derived cytokine that is upregulated in adipose tissue in obesity. Upon binding its receptor (OSMR), OSM induces the phosphorylation of the p66 subunit of Src homology 2 domain-containing transforming protein 1 (SHC1), called p66Shc, and activates the extracellular signal-related kinase (ERK) pathway. Mice with adipocyte-specific OSMR deletion (OsmrFKO) are insulin resistant and exhibit adipose tissue inflammation, suggesting that intact adipocyte OSM-OSMR signaling is necessary for maintaining adipose tissue health. How OSM affects specific adipocyte functions is still unclear. Here, we examined the effects of OSM on adipocyte lipolysis. We treated 3T3-L1 adipocytes with OSM, insulin, and/or inhibitors of SHC1 and ERK and measured glycerol release. We also measured phosphorylation of p66Shc, ERK, and insulin receptor substrate-1 (IRS1) and the expression of lipolysis-associated genes in OSM-exposed 3T3-L1 adipocytes and primary adipocytes from control and OsmrFKO mice. We found that OSM induces adipocyte lipolysis via a p66Shc-ERK pathway and inhibits the suppression of lipolysis by insulin. Further, OSM induces phosphorylation of inhibitory IRS1 residues. We conclude that OSM is a stimulator of lipolysis and inhibits adipocyte insulin response. Future studies will determine how these roles of OSM affect adipose tissue function in health and disease.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
International journal of molecular sciences - 23(2022), 9 vom: 23. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bailey, Jennifer L [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.05.2022 Date Revised 30.11.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/ijms23094689 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM340860219 |
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| 245 | 1 | 0 | |a Oncostatin M Induces Lipolysis and Suppresses Insulin Response in 3T3-L1 Adipocytes |
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| 500 | |a Date Revised 30.11.2022 | ||
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| 520 | |a Oncostatin M (OSM) is an immune cell-derived cytokine that is upregulated in adipose tissue in obesity. Upon binding its receptor (OSMR), OSM induces the phosphorylation of the p66 subunit of Src homology 2 domain-containing transforming protein 1 (SHC1), called p66Shc, and activates the extracellular signal-related kinase (ERK) pathway. Mice with adipocyte-specific OSMR deletion (OsmrFKO) are insulin resistant and exhibit adipose tissue inflammation, suggesting that intact adipocyte OSM-OSMR signaling is necessary for maintaining adipose tissue health. How OSM affects specific adipocyte functions is still unclear. Here, we examined the effects of OSM on adipocyte lipolysis. We treated 3T3-L1 adipocytes with OSM, insulin, and/or inhibitors of SHC1 and ERK and measured glycerol release. We also measured phosphorylation of p66Shc, ERK, and insulin receptor substrate-1 (IRS1) and the expression of lipolysis-associated genes in OSM-exposed 3T3-L1 adipocytes and primary adipocytes from control and OsmrFKO mice. We found that OSM induces adipocyte lipolysis via a p66Shc-ERK pathway and inhibits the suppression of lipolysis by insulin. Further, OSM induces phosphorylation of inhibitory IRS1 residues. We conclude that OSM is a stimulator of lipolysis and inhibits adipocyte insulin response. Future studies will determine how these roles of OSM affect adipose tissue function in health and disease | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a adipocyte | |
| 650 | 4 | |a insulin resistance | |
| 650 | 4 | |a lipolysis | |
| 650 | 4 | |a oncostatin M | |
| 650 | 4 | |a oncostatin M receptor | |
| 650 | 7 | |a Insulin |2 NLM | |
| 650 | 7 | |a Insulin, Regular, Human |2 NLM | |
| 650 | 7 | |a SHC1 protein, human |2 NLM | |
| 650 | 7 | |a Src Homology 2 Domain-Containing, Transforming Protein 1 |2 NLM | |
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| 700 | 1 | |a Boudreau, Anik |e verfasserin |4 aut | |
| 700 | 1 | |a Elks, Carrie M |e verfasserin |4 aut | |
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