title: EPA-enriched phospholipids ameliorate cancer-associated cachexia mainly via inhibiting lipolysis.
abstract: Excessive loss of fat mass is considered as a key feature of body weight loss in cancer-associated cachexia (CAC). It affects the efficacy and tolerability of cancer therapy and reduces the quality and length of cancer patients' lives. The aim of the present study was to evaluate the effects of EPA-enriched phospholipids (EPA-PL) derived from starfish Asterias amurensis on cachectic weight loss in mice bearing S180 ascitic tumor, and TNF-α-stimulated lipolysis in 3T3-L1 adipocytes and to elucidate the possible mechanisms involved. Our findings revealed that oral administration of EPA-PL at 100 mg per kg body weight (BW) per day for 14 days prevented body weight loss in CAC mice by preserving the white adipose tissue (WAT) mass. We found that serum levels of nonesterified fatty acid (NEFA) and pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α) and interleukin (IL)-6 increased in CAC mice but decreased significantly after oral treatment of EPA-PL. In addition, EPA-PL treatment also suppressed the overexpression of several key lipolytic factors and raised the mRNA levels of some adipogenic factors in the WAT of CAC mice. Moreover, treatment of EPA-PL (200 and 400 μM) markedly inhibited TNF-α-stimulated lipolysis in adipocytes. Furthermore, the antilipolytic effects of EPA-PL were stimulated by the extracellular signal-regulated kinase 1/2 (ERK 1/2) inhibitor PD 98059 and blocked via the AMP-activated protein kinase (AMPK) inhibitor compound C and the phosphoinositide-3-kinase (PI3K) inhibitor LY 294002. Taken together, these data suggest that the dietary EPA-PL ameliorates CAC mainly via inhibiting lipolysis and at least in part for recovering the function of adipogenesis.
authors.affiliation: Faculty of Fisheries Sciences, Hokkaido University, 3-1-1 Minato-cho, Hakodate, Hokkaido 041-8611, Japan. kore@fish.hokudai.ac.jp wangyuming@ouc.edu.cn and College of Food Science and Engineering, Ocean University of China, No. 5 Yu-Shan Road, Qingdao, Shandong Province 266003, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Du
authors.affiliation: Faculty of Fisheries Sciences, Hokkaido University, 3-1-1 Minato-cho, Hakodate, Hokkaido 041-8611, Japan. kore@fish.hokudai.ac.jp wangyuming@ouc.edu.cn and College of Food Science and Engineering, Ocean University of China, No. 5 Yu-Shan Road, Qingdao, Shandong Province 266003, People's Republic of China.
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Yang
authors.affiliation: College of Food Science and Engineering, Ocean University of China, No. 5 Yu-Shan Road, Qingdao, Shandong Province 266003, People's Republic of China.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Wang
authors.affiliation: College of Food Science and Engineering, Ocean University of China, No. 5 Yu-Shan Road, Qingdao, Shandong Province 266003, People's Republic of China.
authors.forename: Chang-Hu
authors.initials: CH
authors.lastname: Xue
authors.affiliation: Faculty of Fisheries Sciences, Hokkaido University, 3-1-1 Minato-cho, Hakodate, Hokkaido 041-8611, Japan. kore@fish.hokudai.ac.jp wangyuming@ouc.edu.cn.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kurihara
authors.affiliation: Faculty of Fisheries Sciences, Hokkaido University, 3-1-1 Minato-cho, Hakodate, Hokkaido 041-8611, Japan. kore@fish.hokudai.ac.jp wangyuming@ouc.edu.cn.
authors.forename: Koretaro
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002100:Cachexia / Q000150:complications / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects; D015118:Eicosapentaenoic Acid / Q000032:analysis / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000150:complications*; D010743:Phospholipids / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D005230:Fatty Acids, Nonesterified; D010743:Phospholipids; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015118:Eicosapentaenoic Acid