Loss of BIM increases mitochondrial oxygen consumption and lipid oxidation, reduces adiposity and improves insulin sensitivity in mice
Journal article
Wali, Jibran A., Galic, Sandra, Tan, Christina Y. R., Gurzov, Esteban N., Frazier, Ann E., Connor, Timothy, Ge, Jingjing, Pappas, Evan G., Stroud, David, Varanasi, L. Chitra, Selck, Claudia, Ryan, Michael T., Thorburn, David R., Kemp, Bruce, Krishnamurthy, Balasubramanian, Kay, Thomas W. H., McGee, S. L. and Thomas, Helen. (2018). Loss of BIM increases mitochondrial oxygen consumption and lipid oxidation, reduces adiposity and improves insulin sensitivity in mice. Cell Death and Differentiation. 25(1), pp. 217 - 225. https://doi.org/10.1038/cdd.2017.168
Authors | Wali, Jibran A., Galic, Sandra, Tan, Christina Y. R., Gurzov, Esteban N., Frazier, Ann E., Connor, Timothy, Ge, Jingjing, Pappas, Evan G., Stroud, David, Varanasi, L. Chitra, Selck, Claudia, Ryan, Michael T., Thorburn, David R., Kemp, Bruce, Krishnamurthy, Balasubramanian, Kay, Thomas W. H., McGee, S. L. and Thomas, Helen |
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Abstract | BCL-2 proteins are known to engage each other to determine the fate of a cell after a death stimulus. However, their evolutionary conservation and the many other reported binding partners suggest an additional function not directly linked to apoptosis regulation. To identify such a function, we studied mice lacking the BH3-only protein BIM. BIM−/− cells had a higher mitochondrial oxygen consumption rate that was associated with higher mitochondrial complex IV activity. The consequences of increased oxygen consumption in BIM−/− mice were significantly lower body weights, reduced adiposity and lower hepatic lipid content. Consistent with reduced adiposity, BIM−/− mice had lower fasting blood glucose, improved insulin sensitivity and hepatic insulin signalling. Lipid oxidation was increased in BIM−/− mice, suggesting a mechanism for their metabolic phenotype. Our data suggest a role for BIM in regulating mitochondrial bioenergetics and metabolism and support the idea that regulation of metabolism and cell death are connected. |
Year | 2018 |
Journal | Cell Death and Differentiation |
Journal citation | 25 (1), pp. 217 - 225 |
Publisher | Nature Publishing Group |
ISSN | 1350-9047 |
Digital Object Identifier (DOI) | https://doi.org/10.1038/cdd.2017.168 |
Scopus EID | 2-s2.0-85048459901 |
Page range | 217 - 225 |
Research Group | Mary MacKillop Institute for Health Research |
Publisher's version | File Access Level Controlled |
Place of publication | United Kingdom |
Editors | G. Melino |
https://acuresearchbank.acu.edu.au/item/89vqy/loss-of-bim-increases-mitochondrial-oxygen-consumption-and-lipid-oxidation-reduces-adiposity-and-improves-insulin-sensitivity-in-mice
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