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Active Ghrelin Levels and Active to Total Ghrelin Ratio in Cancer-Induced Cachexia

Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism (J.M.G., M.G.-T., R.A.H., G.R.C., M.M.), Oncology (D.E.), and Cardiology (D.M.) and the Huffington Center on Aging (J.M.G., G.T., R.G.S.), Baylor College of Medicine, and Michael E. DeBakey Veterans Affairs Medical Center (J.M.G., M.G.-T., R.A.H., G.T., D.E., D.M., G.R.C., M.M.), Houston, Texas 77030

Address all correspondence and requests for reprints to: José M. Garcia, Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Boulevard, Houston, Texas 77030. E-mail: jgarcia1{at}bcm.tmc.edu.

Anorexia and weight loss are negative prognostic factors in patients with cancer. Although total ghrelin levels are increased in energy-negative states, levels of the biologically active octanoylated ghrelin and the anorexigenic peptide YY (PYY) have not been reported in patients with cancer-induced cachexia. We hypothesized that abnormal ghrelin and/or PYY levels contribute to cancer-induced cachexia. We evaluated 21 patients with cancer-induced cachexia; 24 cancer patients without cachexia; and 23 age-, sex-, race-, and BMI-matched subjects without cancer. Active ghrelin levels and the active to total ghrelin ratio were significantly increased in subjects with cancer-induced cachexia, compared with cancer and noncancer controls. PYY levels were similar among groups. Appetite measured by a visual analog scale was not increased in subjects with cachexia. The increase in active ghrelin levels is likely to be a compensatory response to weight loss. Cachexia may be a state of ghrelin resistance because appetite does not correlate with ghrelin levels. Changes in the active to total ghrelin ratio suggest that a mechanism other than increased secretion must be responsible for the increase in active ghrelin levels. PYY is unlikely to play an important role in cancer-induced cachexia.

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