GHSR-1a is not Required for Ghrelin's Anti-inflammatory and Fat-sparing Effects in Cancer Cachexia

Liu, H.; Luo, J.; Guillory, B.; Chen, J.-a.; Zang, P.; Yoeli, J. K.; Hernandez, Y.; Lee, I.; Anderson, B.; Storie, M. J.; Tewnion, A.; Garcia, J.

doi:10.1101/866376

bioRxiv · 10.1101/866376

GHSR-1a is not Required for Ghrelin's Anti-inflammatory and Fat-sparing Effects in Cancer Cachexia

Liu, H.·Luo, J.·Guillory, B.·Chen, J.-a.·Zang, P.·Yoeli, J. K.·Hernandez, Y.·Lee, I.·Anderson, B.·Storie, M. J.·Tewnion, A.·Garcia, J.

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Abstract

Adipose tissue (AT) atrophy is a hallmark of cancer cachexia contributing to increased morbidity/mortality. Ghrelin has been proposed as a treatment for cancer cachexia partly by preventing AT atrophy. However, the mechanisms mediating ghrelins effects are incompletely understood, including the extent to which its only known receptor, GHSR-1a, is required for these effects. This study characterizes the pathways involved in AT atrophy in the Lewis Lung Carcinoma (LLC)-induced cachexia model and those mediating the effects of ghrelin in Ghsr+/+ and Ghsr-/- mice. We show that LLC causes AT atrophy by inducing anorexia, and increasing AT inflammation, thermogenesis and energy expenditure. These changes were greater in Ghsr-/-. Ghrelin administration prevented LLC-induced anorexia only in Ghsr+/+, but prevented WAT inflammation and atrophy in both genotypes, although its effects were greater in Ghsr+/+. LLC-induced increases in BAT inflammation, WAT and BAT thermogenesis, and energy expenditure were not affected by ghrelin. In conclusion, ghrelin ameliorates WAT inflammation, fat atrophy and anorexia in LLC-induced cachexia. GHSR-1a is required for ghrelins orexigenic effect but not for its anti-inflammatory or fat-sparing effects.

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Liu, H., Luo, J., Guillory, B., Chen, J.-a., Zang, P., Yoeli, J. K., Hernandez, Y., Lee, I., Anderson, B., Storie, M. J., Tewnion, A., Garcia, J.. 2019-12-06. GHSR-1a is not Required for Ghrelin's Anti-inflammatory and Fat-sparing Effects in Cancer Cachexia. https://doi.org/10.1101/866376

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