Myeloid differentiation factor 88 (MyD88)-deficiency increases risk of diabetes in mice.
BACKGROUND: Multiple lines of evidence suggest innate immune response pathways to be involved in the development of obesity-associated diabetes although the molecular mechanism underling the disease is unknown. Recent observations suggest that saturated fatty acids can act as a ligand for toll-like...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2932727?pdf=render |
| _version_ | 1818584558021378048 |
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| author | Toru Hosoi Shota Yokoyama Suguru Matsuo Shizuo Akira Koichiro Ozawa |
| author_facet | Toru Hosoi Shota Yokoyama Suguru Matsuo Shizuo Akira Koichiro Ozawa |
| author_sort | Toru Hosoi |
| collection | DOAJ |
| description | BACKGROUND: Multiple lines of evidence suggest innate immune response pathways to be involved in the development of obesity-associated diabetes although the molecular mechanism underling the disease is unknown. Recent observations suggest that saturated fatty acids can act as a ligand for toll-like receptor (TLR) 4, which is thought to mediate obesity-associated insulin resistance. Myeloid differentiation factor 88 (MyD88) is an adapter protein for TLR/IL-1 receptor signaling, which is involved in the activation of inflammatory pathways. To evaluate molecular mechanisms linking obesity-associated diabetes down-stream of TLR4, we investigated physiological role of MyD88 in high-fat diet (HFD)-induced obesity. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we found MyD88-deficient mice fed a HFD had increased circulating levels of insulin, leptin and cholesterol, as well as liver dysfunction (increased induction of ALT levels, increased activation of JNK and cleavage of PARP), which were linked to the onset of severe diabetes. On the other hand, TNF-alpha would not be involved in HFD-induced diabetes in MyD88-deficient mice, because TNF-alpha level was attenuated in MyD88-deficient mice fed with HFD. CONCLUSIONS/SIGNIFICANCE: The present finding of an unexpected role for MyD88 in preventing diabetes may provide a potential novel target/strategy for treating metabolic syndrome. |
| first_indexed | 2024-12-16T08:23:05Z |
| format | Article |
| id | doaj.art-fbcf21b0cd4c4a9fb4a70e97d4e7c5d6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T08:23:05Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-fbcf21b0cd4c4a9fb4a70e97d4e7c5d62022-12-21T22:38:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0159e1248910.1371/journal.pone.0012537Myeloid differentiation factor 88 (MyD88)-deficiency increases risk of diabetes in mice.Toru HosoiShota YokoyamaSuguru MatsuoShizuo AkiraKoichiro OzawaBACKGROUND: Multiple lines of evidence suggest innate immune response pathways to be involved in the development of obesity-associated diabetes although the molecular mechanism underling the disease is unknown. Recent observations suggest that saturated fatty acids can act as a ligand for toll-like receptor (TLR) 4, which is thought to mediate obesity-associated insulin resistance. Myeloid differentiation factor 88 (MyD88) is an adapter protein for TLR/IL-1 receptor signaling, which is involved in the activation of inflammatory pathways. To evaluate molecular mechanisms linking obesity-associated diabetes down-stream of TLR4, we investigated physiological role of MyD88 in high-fat diet (HFD)-induced obesity. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we found MyD88-deficient mice fed a HFD had increased circulating levels of insulin, leptin and cholesterol, as well as liver dysfunction (increased induction of ALT levels, increased activation of JNK and cleavage of PARP), which were linked to the onset of severe diabetes. On the other hand, TNF-alpha would not be involved in HFD-induced diabetes in MyD88-deficient mice, because TNF-alpha level was attenuated in MyD88-deficient mice fed with HFD. CONCLUSIONS/SIGNIFICANCE: The present finding of an unexpected role for MyD88 in preventing diabetes may provide a potential novel target/strategy for treating metabolic syndrome.http://europepmc.org/articles/PMC2932727?pdf=render |
| spellingShingle | Toru Hosoi Shota Yokoyama Suguru Matsuo Shizuo Akira Koichiro Ozawa Myeloid differentiation factor 88 (MyD88)-deficiency increases risk of diabetes in mice. PLoS ONE |
| title | Myeloid differentiation factor 88 (MyD88)-deficiency increases risk of diabetes in mice. |
| title_full | Myeloid differentiation factor 88 (MyD88)-deficiency increases risk of diabetes in mice. |
| title_fullStr | Myeloid differentiation factor 88 (MyD88)-deficiency increases risk of diabetes in mice. |
| title_full_unstemmed | Myeloid differentiation factor 88 (MyD88)-deficiency increases risk of diabetes in mice. |
| title_short | Myeloid differentiation factor 88 (MyD88)-deficiency increases risk of diabetes in mice. |
| title_sort | myeloid differentiation factor 88 myd88 deficiency increases risk of diabetes in mice |
| url | http://europepmc.org/articles/PMC2932727?pdf=render |
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