This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Laurencikiene, J. Articles by Arner, P. Search for Related Content PubMed PubMed Citation Articles by Laurencikiene, J. Articles by Arner, P.

Evidence for an Important Role of CIDEA in Human Cancer Cachexia

Departments of ¹ Medicine and ² Surgery, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden; ³ Institut National de la Santé et de la Recherche Médicale, U858, Obesity Research Laboratory, ⁴ Louis Bugnard Institute, IFR31, Paul Sabatier University; and ⁵ CHU de Toulouse, Biochemistry Laboratory, Biology Institute of Purpan, Toulouse, France

Requests for reprints: Peter Arner, Karolinska Institutet, Karolinska University Hospital, Huddinge, CME-M61, SE-141 86 Stockholm, Sweden. Phone: 46-8-58582342; Fax: 46-8-58582347. E-mail: peter.arner{at}ki.se.

Key Words: Fat cells • Fatty acid oxidation • Weight loss • Respiratory quotient • Lipolysis • Transfection • mRNA

Loss of fat mass in cancer cachexia is linked to increased adipocyte lipolysis; however, the fate of the excess fatty acids (FA) generated by lipolysis is not known. We investigated if the adipocyte-specific gene cell death–inducing DNA fragmentation factor-–like effector A (CIDEA) could be involved. CIDEA mRNA expression was assessed in s.c. white adipose tissue from 23 cancer cachexia patients, 17 weight-stable cancer patients, and 8 noncancer patients. CIDEA was also overexpressed in adipocytes in vitro. CIDEA expression was increased in cancer cachexia (P < 0.05) and correlated with elevated levels of FAs and reported weight loss (P < 0.001). CIDEA overexpression in vitro increased FA oxidation 2- to 4-fold (P < 0.01), decreased glucose oxidation by 40% (P < 0.01), increased the expression of pyruvate dehydrogenase kinase (PDK) 1 and PDK4 (P < 0.01), and enhanced the phosphorylation (inactivation) of the pyruvate dehydrogenase complex (PDC). Inactivation of PDC facilitates FA oxidation by favoring the metabolism of FAs over glucose to acetyl-CoA. In accordance with the in vitro data, PDK1 and PDK4 expression correlated strongly with CIDEA expression in white adipose tissue (P < 0.001). We conclude that CIDEA is involved in adipose tissue loss in cancer cachexia and this may, at least in part, be due to its ability to inactivate PDC, thereby switching substrate oxidation in human fat cells from glucose to FAs. [Cancer Res 2008;68(22):9247–54]

This article has been cited by other articles:

				B. M. Stenson, M. Ryden, K. R. Steffensen, K. Wahlen, A. T. Pettersson, J. W. Jocken, P. Arner, and J. Laurencikiene Activation of Liver X Receptor Regulates Substrate Oxidation in White Adipocytes Endocrinology, September 1, 2009; 150(9): 4104 - 4113. [Abstract] [Full Text] [PDF]