Abstract:
:Cachexia, defined as an involuntary weight loss ≥ 5%, is a serious and dose-limiting side effect of chemotherapy that decreases survival in cancer patients. Alterations in lipid metabolism are thought to cause the lipodystrophy commonly associated with cachexia. Ghrelin has been proposed to ameliorate the alterations in lipid metabolism due to its orexigenic and anabolic properties. However, the mechanisms of action through which ghrelin could potentially ameliorate chemotherapy-associated cachexia have not been elucidated. The objectives of this study were to identify mechanisms by which the chemotherapeutic agent cisplatin alters lipid metabolism and to establish the role of ghrelin in reversing cachexia. Cisplatin-induced weight and fat loss were prevented by ghrelin. Cisplatin increased markers of lipolysis in white adipose tissue (WAT) and of β-oxidation in liver and WAT and suppressed lipogenesis in liver, WAT, and muscle. Ghrelin prevented the imbalance between lipolysis, β-oxidation, and lipogenesis in WAT and muscle. Pair-feeding experiments demonstrated that the effects of cisplatin and ghrelin on lipogenesis, but not on lipolysis and β-oxidation, were due to a reduction in food intake. Thus, ghrelin prevents cisplatin-induced weight and fat loss by restoring adipose tissue functionality. An increase in caloric intake further enhances the anabolic effects of ghrelin.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Garcia JM,Scherer T,Chen JA,Guillory B,Nassif A,Papusha V,Smiechowska J,Asnicar M,Buettner C,Smith RGdoi
10.1210/en.2013-1179subject
Has Abstractpub_date
2013-09-01 00:00:00pages
3118-29issue
9eissn
0013-7227issn
1945-7170pii
en.2013-1179journal_volume
154pub_type
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