RT Journal Article
SR Electronic
T1 GHSR-1a is not Required for Ghrelin’s Anti-inflammatory and Fat-sparing Effects in Cancer Cachexia
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 866376
DO 10.1101/866376
A1 Haiming Liu
A1 Jiaohua Luo
A1 Bobby Guillory
A1 Ji-an Chen
A1 Pu Zang
A1 Jordan K. Yoeli
A1 Yamileth Hernandez
A1 Ian (In-gi) Lee
A1 Barbara Anderson
A1 Mackenzie Storie
A1 Alison Tewnion
A1 Jose M. Garcia
YR 2019
UL http://biorxiv.org/content/early/2019/12/06/866376.abstract
AB 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 ghrelin’s 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 ghrelin’s orexigenic effect but not for its anti-inflammatory or fat-sparing effects.