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An Inhibitory Role of Piceatannol in Cancer Cachexia‐Associated Lipolysis In Vitro
Author(s) -
Kershaw Jonathan,
Kim KeeHong
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.688.10
Subject(s) - lipolysis , piceatannol , adipose triglyceride lipase , endocrinology , adipose tissue , medicine , chemistry , adipocyte , lipogenesis , cancer research , resveratrol , biochemistry
Cancer‐associated cachexia (CAC) is the debilitating “wasting” syndrome observed in many cancer patients, and is the estimated direct cause of death in up to 20% of all cancer mortalities. Although the causes of CAC are complex, increasing evidence suggests that preventing adipocyte lipolysis may preserve both lean muscle and adipose mass. Indeed, adipose loss in CAC is primarily due to increased lipolysis. Currently, there are no effective treatments of CAC. We recently identified piceatannol, a resveratrol analogue, as an anti‐adipogenic small molecule. We further found that piceatannol, unlike resveratrol, inhibits lipolysis in mature adipocytes both in vitro and in vivo. The objectives of this study were to first establish in vitro models of cancer‐associated lipolysis, and then to investigate whether piceatannol prevented lipolysis in CAC‐related conditions. Cancer‐associated lipolysis was modeled in murine 3T3‐L1 adipocytes using both pancreatic cancer‐cell (Panc‐1) conditioned media (CM) and the cachexia‐associated cytokines TNF‐alpha and interleukin‐6. These models significantly increased lipolysis. Of interest, piceatannol lowered cancer‐associated lipolysis by at least 50% in both CM and cytokine induced lipolysis in adipocytes. Molecular analysis revealed that piceatannol induced autophagy‐mediated protein degradation of adipose triglyceride lipase (ATGL), which catalyzes the initial and rate‐limiting step of lipolysis in adipocytes, and comparative gene identification‐58 (CGI‐58), an ATGL co‐activator. Gene expression of ATGL was unaffected by piceatannol treatment, further supporting the hypothesis that piceatannol regulates lipolysis post‐transcriptionally. In addition to revealing the role of piceatannol in reducing cancer‐associated lipolysis, this study characterized the effect of cancer CM on expression of key lipid metabolism machinery. Preventing adipose loss in CAC can enhance chemotherapy response, increase survival outcomes, and improve quality of life. This study provides a theoretical basis for using piceatannol or piceatannol‐rich foods as alternative medicine to supplement cancer treatment. Support or Funding Information This research was supported by NIH, 5R03CA184544‐01A1 and the USDA‐NIFA National Needs Fellowship.