IL-1 signaling in obesity-induced hepatic lipogenesis and steatosis.
Non-alcoholic fatty liver disease is prevalent in human obesity and type 2 diabetes, and is characterized by increases in both hepatic triglyceride accumulation (denoted as steatosis) and expression of pro-inflammatory cytokines such as IL-1β. We report here that the development of hepatic steatosis...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4162604?pdf=render |
| _version_ | 1819259579940208640 |
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| author | Kimberly A Negrin Rachel J Roth Flach Marina T DiStefano Anouch Matevossian Randall H Friedline DaeYoung Jung Jason K Kim Michael P Czech |
| author_facet | Kimberly A Negrin Rachel J Roth Flach Marina T DiStefano Anouch Matevossian Randall H Friedline DaeYoung Jung Jason K Kim Michael P Czech |
| author_sort | Kimberly A Negrin |
| collection | DOAJ |
| description | Non-alcoholic fatty liver disease is prevalent in human obesity and type 2 diabetes, and is characterized by increases in both hepatic triglyceride accumulation (denoted as steatosis) and expression of pro-inflammatory cytokines such as IL-1β. We report here that the development of hepatic steatosis requires IL-1 signaling, which upregulates Fatty acid synthase to promote hepatic lipogenesis. Using clodronate liposomes to selectively deplete liver Kupffer cells in ob/ob mice, we observed remarkable amelioration of obesity-induced hepatic steatosis and reductions in liver weight, triglyceride content and lipogenic enzyme expressions. Similar results were obtained with diet-induced obese mice, although visceral adipose tissue macrophage depletion also occurred in response to clodronate liposomes in this model. There were no differences in the food intake, whole body metabolic parameters, serum β-hydroxybutyrate levels or lipid profiles due to clodronate-treatment, but hepatic cytokine gene expressions including IL-1β were decreased. Conversely, treatment of primary mouse hepatocytes with IL-1β significantly increased triglyceride accumulation and Fatty acid synthase expression. Furthermore, the administration of IL-1 receptor antagonist to obese mice markedly reduced obesity-induced steatosis and hepatic lipogenic gene expression. Collectively, our findings suggest that IL-1β signaling upregulates hepatic lipogenesis in obesity, and is essential for the induction of pathogenic hepatic steatosis in obese mice. |
| first_indexed | 2024-12-23T19:12:16Z |
| format | Article |
| id | doaj.art-66320ee6e11440dabb45ca7cea33b6bf |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T19:12:16Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-66320ee6e11440dabb45ca7cea33b6bf2022-12-21T17:34:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10726510.1371/journal.pone.0107265IL-1 signaling in obesity-induced hepatic lipogenesis and steatosis.Kimberly A NegrinRachel J Roth FlachMarina T DiStefanoAnouch MatevossianRandall H FriedlineDaeYoung JungJason K KimMichael P CzechNon-alcoholic fatty liver disease is prevalent in human obesity and type 2 diabetes, and is characterized by increases in both hepatic triglyceride accumulation (denoted as steatosis) and expression of pro-inflammatory cytokines such as IL-1β. We report here that the development of hepatic steatosis requires IL-1 signaling, which upregulates Fatty acid synthase to promote hepatic lipogenesis. Using clodronate liposomes to selectively deplete liver Kupffer cells in ob/ob mice, we observed remarkable amelioration of obesity-induced hepatic steatosis and reductions in liver weight, triglyceride content and lipogenic enzyme expressions. Similar results were obtained with diet-induced obese mice, although visceral adipose tissue macrophage depletion also occurred in response to clodronate liposomes in this model. There were no differences in the food intake, whole body metabolic parameters, serum β-hydroxybutyrate levels or lipid profiles due to clodronate-treatment, but hepatic cytokine gene expressions including IL-1β were decreased. Conversely, treatment of primary mouse hepatocytes with IL-1β significantly increased triglyceride accumulation and Fatty acid synthase expression. Furthermore, the administration of IL-1 receptor antagonist to obese mice markedly reduced obesity-induced steatosis and hepatic lipogenic gene expression. Collectively, our findings suggest that IL-1β signaling upregulates hepatic lipogenesis in obesity, and is essential for the induction of pathogenic hepatic steatosis in obese mice.http://europepmc.org/articles/PMC4162604?pdf=render |
| spellingShingle | Kimberly A Negrin Rachel J Roth Flach Marina T DiStefano Anouch Matevossian Randall H Friedline DaeYoung Jung Jason K Kim Michael P Czech IL-1 signaling in obesity-induced hepatic lipogenesis and steatosis. PLoS ONE |
| title | IL-1 signaling in obesity-induced hepatic lipogenesis and steatosis. |
| title_full | IL-1 signaling in obesity-induced hepatic lipogenesis and steatosis. |
| title_fullStr | IL-1 signaling in obesity-induced hepatic lipogenesis and steatosis. |
| title_full_unstemmed | IL-1 signaling in obesity-induced hepatic lipogenesis and steatosis. |
| title_short | IL-1 signaling in obesity-induced hepatic lipogenesis and steatosis. |
| title_sort | il 1 signaling in obesity induced hepatic lipogenesis and steatosis |
| url | http://europepmc.org/articles/PMC4162604?pdf=render |
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