title: Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism.
abstract: Lipids are essential cellular components and energy sources of living organisms, and altered lipid composition is increasingly recognized as a signature of cancer. We performed lipidomic analysis in a series of hepatocellular carcinoma (HCC) cells and identified over 1,700 intact lipids originating from three major lipid categories. Comparative lipidomic screening revealed that 93 significantly changed lipids and decreased palmitic acyl (C16:0)-containing glycerophospholipids were positively associated with metastatic abilities of HCC cells. Furthermore, both in vitro and in vivo experiments demonstrated that C16:0 incubation specifically reduced malignant cell proliferation, impaired cell invasiveness, and suppressed tumor growth in mouse xenograft models. Biochemical experiments demonstrated that C16:0 treatment decreased cell membrane fluidity and limited glucose metabolism. A phosphoproteomics approach further revealed such C16:0 incubation attenuated phosphorylation levels of mammalian target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) pathway proteins. Multiple reaction monitoring analysis of 443 lipid molecules showed 8 reduced C16:0-containing lipids out of total 10 altered lipids when cancer tissues were compared with adjacent nontumor tissues in a cohort of clinical HCC specimens (P < 0.05).
  
  
  
  These data collectively demonstrate the biomedical potential of using altered lipid metabolism as a diagnostic marker for cancerous cells and open an opportunity for treating aggressive HCCs by targeting altered C16:0 metabolism. (Hepatology 2017;66:432-448).
authors.affiliation: Department of Systems Biology for Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Systems Biology for Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Shanghai Institute for Food and Drug Control, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Systems Biology for Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai, China.|Department of Chemistry, Fudan University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Systems Biology for Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Systems Biology for Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Department of Chemistry, Fudan University, Shanghai, China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Chemistry, Fudan University, Shanghai, China.
authors.forename: Guoquan
authors.initials: G
authors.lastname: Yan
authors.affiliation: Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Systems Biology for Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai, China.|Department of Chemistry, Fudan University, Shanghai, China.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Systems Biology for Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai, China.|Department of Chemistry, Fudan University, Shanghai, China.
authors.forename: Huali
authors.initials: H
authors.lastname: Shen
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D056945:Hep G2 Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D051379:Mice; D008819:Mice, Nude; D019308:Palmitic Acid / Q000494:pharmacology*; D011897:Random Allocation; D012680:Sensitivity and Specificity; D013844:Thiazoles / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: C000617853:GW 506033X; D007211:Indoles; D013844:Thiazoles; D019308:Palmitic Acid; D005947:Glucose