Inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotype
Abstract Background The consumption of large amounts of dietary fats can trigger an inflammatory response in the hypothalamus and contribute to the dysfunctional control of caloric intake and energy expenditure commonly present in obesity. The objective of this study was to identify chemokine-relate...
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| Format: | Article |
| Language: | English |
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BMC
2017-09-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | http://link.springer.com/article/10.1186/s12974-017-0956-9 |
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| author | Milena Fioravante Bruna Bombassaro Albina F. Ramalho Nathalia R. Dragano Joseane Morari Carina Solon Natalia Tobar Celso D. Ramos Licio A. Velloso |
| author_facet | Milena Fioravante Bruna Bombassaro Albina F. Ramalho Nathalia R. Dragano Joseane Morari Carina Solon Natalia Tobar Celso D. Ramos Licio A. Velloso |
| author_sort | Milena Fioravante |
| collection | DOAJ |
| description | Abstract Background The consumption of large amounts of dietary fats can trigger an inflammatory response in the hypothalamus and contribute to the dysfunctional control of caloric intake and energy expenditure commonly present in obesity. The objective of this study was to identify chemokine-related transcripts that could be involved in the early stages of diet-induced hypothalamic inflammation. Methods We used immunoblot, PCR array, real-time PCR, immunofluorescence staining, glucose and insulin tolerance tests, and determination of general metabolic parameters to evaluate markers of inflammation, body mass variation, and glucose tolerance in mice fed a high-fat diet. Results Using a real-time PCR array, we identified leukemia inhibitory factor as a chemokine/cytokine undergoing a rapid increase in the hypothalamus of obesity-resistant and a rapid decrease in the hypothalamus of obesity-prone mice fed a high-fat diet for 1 day. We hypothesized that the increased hypothalamic expression of leukemia inhibitory factor could contribute to the protective phenotype of obesity-resistant mice. To test this hypothesis, we immunoneutralized hypothalamic leukemia inhibitory factor and evaluated inflammatory and metabolic parameters. The immunoneutralization of leukemia inhibitory factor in the hypothalamus of obesity-resistant mice resulted in increased body mass gain and increased adiposity. Body mass gain was mostly due to increased caloric intake and reduced spontaneous physical activity. This modification in the phenotype was accompanied by increased expression of inflammatory cytokines in the hypothalamus. In addition, the inhibition of hypothalamic leukemia inhibitory factor was accompanied by glucose intolerance and insulin resistance. Conclusion Hypothalamic expression of leukemia inhibitory factor may protect mice from the development of diet-induced obesity; the inhibition of this protein in the hypothalamus transforms obesity-resistant into obesity-prone mice. |
| first_indexed | 2024-12-23T10:56:54Z |
| format | Article |
| id | doaj.art-a3f616d1653841bbb979fcf2e0218206 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-23T10:56:54Z |
| publishDate | 2017-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-a3f616d1653841bbb979fcf2e02182062022-12-21T17:49:45ZengBMCJournal of Neuroinflammation1742-20942017-09-0114111210.1186/s12974-017-0956-9Inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotypeMilena Fioravante0Bruna Bombassaro1Albina F. Ramalho2Nathalia R. Dragano3Joseane Morari4Carina Solon5Natalia Tobar6Celso D. Ramos7Licio A. Velloso8Laboratory of Cell Signaling, University of CampinasLaboratory of Cell Signaling, University of CampinasLaboratory of Cell Signaling, University of CampinasLaboratory of Cell Signaling, University of CampinasLaboratory of Cell Signaling, University of CampinasLaboratory of Cell Signaling, University of CampinasDepartment of Radiology, University of CampinasDepartment of Radiology, University of CampinasLaboratory of Cell Signaling, University of CampinasAbstract Background The consumption of large amounts of dietary fats can trigger an inflammatory response in the hypothalamus and contribute to the dysfunctional control of caloric intake and energy expenditure commonly present in obesity. The objective of this study was to identify chemokine-related transcripts that could be involved in the early stages of diet-induced hypothalamic inflammation. Methods We used immunoblot, PCR array, real-time PCR, immunofluorescence staining, glucose and insulin tolerance tests, and determination of general metabolic parameters to evaluate markers of inflammation, body mass variation, and glucose tolerance in mice fed a high-fat diet. Results Using a real-time PCR array, we identified leukemia inhibitory factor as a chemokine/cytokine undergoing a rapid increase in the hypothalamus of obesity-resistant and a rapid decrease in the hypothalamus of obesity-prone mice fed a high-fat diet for 1 day. We hypothesized that the increased hypothalamic expression of leukemia inhibitory factor could contribute to the protective phenotype of obesity-resistant mice. To test this hypothesis, we immunoneutralized hypothalamic leukemia inhibitory factor and evaluated inflammatory and metabolic parameters. The immunoneutralization of leukemia inhibitory factor in the hypothalamus of obesity-resistant mice resulted in increased body mass gain and increased adiposity. Body mass gain was mostly due to increased caloric intake and reduced spontaneous physical activity. This modification in the phenotype was accompanied by increased expression of inflammatory cytokines in the hypothalamus. In addition, the inhibition of hypothalamic leukemia inhibitory factor was accompanied by glucose intolerance and insulin resistance. Conclusion Hypothalamic expression of leukemia inhibitory factor may protect mice from the development of diet-induced obesity; the inhibition of this protein in the hypothalamus transforms obesity-resistant into obesity-prone mice.http://link.springer.com/article/10.1186/s12974-017-0956-9DiabetesGlucoseInsulinAdipose tissueInflammation |
| spellingShingle | Milena Fioravante Bruna Bombassaro Albina F. Ramalho Nathalia R. Dragano Joseane Morari Carina Solon Natalia Tobar Celso D. Ramos Licio A. Velloso Inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotype Journal of Neuroinflammation Diabetes Glucose Insulin Adipose tissue Inflammation |
| title | Inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotype |
| title_full | Inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotype |
| title_fullStr | Inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotype |
| title_full_unstemmed | Inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotype |
| title_short | Inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotype |
| title_sort | inhibition of hypothalamic leukemia inhibitory factor exacerbates diet induced obesity phenotype |
| topic | Diabetes Glucose Insulin Adipose tissue Inflammation |
| url | http://link.springer.com/article/10.1186/s12974-017-0956-9 |
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