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Liu H, Luo J, Guillory B, Chen JA, Zang P, Yoeli JK, Hernandez Y, Lee II, Anderson B, Storie M, Tewnion A, Garcia JM. Ghrelin ameliorates tumor-induced adipose tissue atrophy and inflammation Ghrelin receptor-dependent and -independent pathways. Oncotarget. 2020 Sep 1; 11(35):3286-3302.
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 and mice. We show that LLC causes AT atrophy by inducing anorexia, and increasing lipolysis, AT inflammation, thermogenesis and energy expenditure. These changes were greater in . Ghrelin administration prevented LLC-induced anorexia only in , but prevented WAT lipolysis, inflammation and atrophy in both genotypes, although its effects were greater in . 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.