Aberrations in Normal Systemic Lipid Metabolism in Ovarian Cancer Patients

Abstract

Numerous investigations have demonstrated altered systemic lipid metabolism in cancer patients, as well as aberrant lipid utilization by tumor cells. The most common measure of altered systemic lipid metabolism in these individuals has been hyperlipidemia. Although cachexia is not generally considered to be associated with gynecologic cancers, this study demonstrates the presence of lipolysis-promoting activity, detectable in sera and ascites of ovarian cancer patients and indices of altered systemic lipid metabolism. Elevated lipolysis promoting activity was detectable in the sera of 7/9 patients and in the ascites of 5/5 patients. Since previous studies have indicated that cancer patients exhibit a 2.5-fold enhancement in hormone-sensitive lipase (HSL) versus normal controls, as a potential mechanism for elevated lipolysis, the ability of ascites-derived factors to induce HSL was examined. The addition of three of four ascites fluids increased the level of HSL in normal adipocytes. All of the patients’ samples exhibited elevated lipid levels versus normal peritoneal fluid. Isolation and analysis of lipids from three ovarian cancer patients revealed four consistent altered lipid parameters compared to normal peritoneal fluid: elevated monoglycerides, diglycerides, and free fatty acids and decreased triacylglycerides. While “classical” cachexia is not a common feature of ovarian cancer, the presence of circulating lipolysis-promoting activity and altered lipid metabolism, generally observed in cachectic individuals, can be demonstrated in these ovarian cancer patients. Based on recent evidence indicating a role of lipids in carcinogenic initiation or promotion, the presence of tumor-derived lipolysis-promoting factor and lipid metabolism alterations may provide a mechanism for the epidemiologically observed association between lipids and certain cancers, including ovarian cancer.