The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
IL-6 and IL-10 Anti-Inflammatory Activity Links Exercise to Hypothalamic Insulin and Leptin Sensitivity through IKKβ and ER Stress Inhibition
Open accessAbstract
Overnutrition caused by overeating is associated with insulin and leptin resistance through IKKbeta activation and endoplasmic reticulum (ER) stress in the hypothalamus. Here we show that physical exercise suppresses hyperphagia and associated hypothalamic IKKbeta/NF-kappaB activation by a mechanism dependent upon the pro-inflammatory cytokine interleukin (IL)-6. The disruption of hypothalamic-specific IL-6 action blocked the beneficial effects of exercise on the re-balance of food intake and insulin and leptin resistance. This molecular mechanism, mediated by physical activity, involves the anti-inflammatory protein IL-10, a core inhibitor of IKKbeta/NF-kappaB signaling and ER stress. We report that exercise and recombinant IL-6 requires IL-10 expression to suppress hyperphagia-related obesity. Moreover, in contrast to control mice, exercise failed to reverse the pharmacological activation of IKKbeta and ER stress in C3H/HeJ mice deficient in hypothalamic IL-6 and IL-10 signaling. Hence, inflammatory signaling in the hypothalamus links beneficial physiological effects of exercise to the central action of insulin and leptin.
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Cites
Tuomilehto, J., Lindström, J., Eriksson, J. G., Valle, T. T., Hämäläinen, H., Ilanne-Parikka, P., Keinänen-Kiukaanniemi, S., Laakso, M., Louheranta, A., Rastas, M., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200105033441801 · Cited by 10,873 · cited 1×
“Exercise has long been reported to reduce body weight and visceral adiposity, increasing the energy expenditure and improving glycaemic control in overweight or T2D patients [15,16].”
BackgroundThe anti-inflammatory effect of exercise
Petersen, A. M. W., & Pedersen, B. K. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00164.2004 · Cited by 3,100 · cited 1×
“. Since the discovery of interleukin (IL)-6 releases from contracting skeletal muscle, accumulating evidence indicates that exercise induces metabolic changes in other organs, such as the liver, the adipose tissue, and hypothalamus, in an IL-6 dependent manner. IL-6 is most often classified as a pro-inflammatory cytok…”
BackgroundInterleukin-6-deficient mice develop mature-onset obesity
Wallenius, V., Wallenius, K., Ahrén, B., Rudling, M., Carlsten, H., Dickson, S. L., Ohlsson, C., & Jansson, J.-O. (2002) · Nature Medicine · doi:10.1038/nm0102-75 · Cited by 1,213
Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity
El-Haschimi, K., Pierroz, D. D., Hileman, S. M., Bjørbæk, C., & Flier, J. S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9842 · Cited by 887
Kuo, L. E., Kitlinska, J. B., Tilan, J. U., Li, L., Baker, S. B., Johnson, M. D., Lee, E. W., Burnett, M. S., Fricke, S. T., Kvetnansky, R., et al. (2007) · Nature Medicine · doi:10.1038/nm1611 · Cited by 656
Physiological roles of muscle-derived interleukin-6 in response to exercise
Pedersen, B. K., & Fischer, C. P. (2007) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/mco.0b013e3280ebb5b3 · Cited by 227
Won, J. C., Jang, P., Namkoong, C., Koh, E. H., Kim, S. K., Park, J., Lee, K., & Kim, M. (2009) · Obesity · doi:10.1038/oby.2009.194 · Cited by 153 · cited 1×
“In accordance with previous studies [7,14,22], we observed that”
ResultPauli, J. R., Ropelle, E. R., Cintra, D. E., Carvalho‐Filho, M. A., Moraes, J. C., De Souza, C. T., Velloso, L. A., Carvalheira, J. B. C., & Saad, M. J. A. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2007.142414 · Cited by 97
Self-citation
Cited by
Inflammatory links between obesity and metabolic disease
Lumeng, C. N., & Saltiel, A. R. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57132 · Cited by 2,319
Hypothalamic inflammation in obesity and metabolic disease
Jais, A., & Brüning, J. C. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88878 · Cited by 474
Obesity in mice with adipocyte-specific deletion of clock component Arntl
Paschos, G. K., Ibrahim, S., Song, W.-L., Kunieda, T., Grant, G., Reyes, T. M., Bradfield, C. A., Vaughan, C. H., Eiden, M., Masoodi, M., et al. (2012) · Nature Medicine · doi:10.1038/nm.2979 · Cited by 465
Leptin and the maintenance of elevated body weight
Pan, W. W., & Myers, M. G. (2018) · Nature reviews. Neuroscience · doi:10.1038/nrn.2017.168 · Cited by 344
Insulin resistance and cancer: The role of insulin and IGFs
Djiogue, S., Nwabo Kamdje, A. H., Vecchio, L., Kipanyula, M. J., Farahna, M., Aldebasi, Y., & Seke Etet, P. F. (2013) · Endocrine Related Cancer · doi:10.1530/erc-12-0324 · Cited by 263
Metadata
- Authors
- Ropelle, E. R., Flores, M. B., Cintra, D. E., Rocha, G. Z., Pauli, J. R., Morari, J., de Souza, C. T., Moraes, J. C., Prada, P. O., Guadagnini, D., Marin, R. M., Oliveira, A. G., Augusto, T. M., Carvalho, H. F., Velloso, L. A., Saad, M. J. A., & Carvalheira, J. B. C.
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-08-24
- Volume
- 8
- Issue
- 8
- Pages
- e1000465
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- OpenAlex
- W2030818171
- Cited by
- 326
- References
- 8
- FWCI
- 9.23
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- gold
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- The paper
- Ropelle, E. R., Flores, M. B., Cintra, D. E., Rocha, G. Z., Pauli, J. R., Morari, J., de Souza, C. T., Moraes, J. C., Prada, P. O., Guadagnini, D., Marin, R. M., Oliveira, A. G., Augusto, T. M., Carvalho, H. F., Velloso, L. A., Saad, M. J. A., & Carvalheira, J. B. C. (2010). IL-6 and IL-10 Anti-Inflammatory Activity Links Exercise to Hypothalamic Insulin and Leptin Sensitivity through IKKβ and ER Stress Inhibition. PLoS Biology. https://doi.org/10.1371/journal.pbio.1000465
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
