期刊
JOURNAL OF PROTEOME RESEARCH
卷 8, 期 11, 页码 5008-5019出版社
AMER CHEMICAL SOC
DOI: 10.1021/pr9004037
关键词
microarray; two-dimensional gel electrophoresis; metabolite; polyamines; hormone-sensitive lipase; high-fat diet
资金
- Swedish Research Council [CH 11284-13-3]
- Crafoord, Torsten and Ragnar Soderberg and Albeit Pahlsson Foundations
- Swedish Diabetes Association
- Novo Nordisk Foundation
- Faculty of Medicine at Lund University
- National Research School in Genomics and Bioinformatics
- Swedish Foundation for Strategic Research
- Knut and Alice Wallenberg Foundation through the Swegene consortium and the Strategic Science Foundation (SSF) CREATE Health centre
Hormone-sensitive lipase (HSL), a key enzyme in fatty acid mobilization from lipid stores, is expressed in the liver and decreased hepatic insulin sensitivity has been reported in our HSL null mouse model. Here, an integrated approach, comprising transcriptomics and proteomics together with targeted metabolite analysis, was used to investigate the liver phenotype of HSL null mice. Oligonucleotide microarray analysis revealed altered expression of genes involved in lipid and polyamine metabolism in HSL null mice compared with wild-type mice and in genes controlling the immune system in mice on high-fat diet versus mice on normal diet Two-dimensional gel electrophoresis followed by MS and/or MS/MS allowed identification of 52 and 22 unique proteins differentially regulated according to the genotype and diet, respectively. Changes were observed mainly for proteins related to metabolism, including several proteins involved in polyamine metabolism or exhibiting methyl transferase activity. Despite the coordinated changes in mRNA and protein levels in polyamine pathways, no significant differences in levels of key polyamine metabolites were detected between the two genotypes This study identifies a link between HSL and polyamine metabolism, which deserves further attention in view of the emerging data suggesting that disturbances in polyamine metabolism may affect insulin sensitivity. The present work also describes a limited correlation between mRNA, protein and metabolite levels, thus, underscoring the importance of integrated approaches.
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