Liver proteomics analysis reveals abnormal metabolism of bile acid and arachidonic acid in Chinese hamsters with type 2 diabetes mellitus

J Proteomics. 2021 May 15:239:104186. doi: 10.1016/j.jprot.2021.104186. Epub 2021 Mar 17.

Abstract

Non-obese, spontaneous, and genetically predisposed type 2 diabetic Chinese hamsters exhibit metabolic abnormalities similar to those observed in human T2DM. Here, tandem mass tag (TMT)-based quantitative proteomics technology was used to screen and identify differentially abundant proteins in the liver that are associated with diabetes in Chinese hamsters. GO and KEGG pathway enrichment analysis were conducted to validate the findings, as well as qRT-PCR and western blotting. In total, 103 proteins were identified in the livers of diabetic hamsters, of which 48 were up-regulated and 55 were down-regulated. KEGG pathway enrichment analysis further demonstrated that linoleic acid metabolism, arachidonic acid metabolism, bile secretion, and other pathways were affected. Moreover, AQP9 and EPHX1 were significantly down-regulated in the bile secretion pathway, whereas PTGES2, Cyp2c27, and Cyp2c70 were associated with the arachidonic acid metabolic pathway. Serum levels of bile acid (BA) and arachidonic acid (AA) in diabetic Chinese hamsters were significantly higher than those in control hamsters. Cumulatively, our findings indicate that the five candidate proteins may be associated with abnormal BA and AA metabolism, suggesting their involvement in pathological changes in the livers of Chinese hamsters with T2DM. SIGNIFICANCE: The liver proteomics of Chinese hamsters describes differentially abundant proteins associated with T2DM, while promoting this animal model as an appropriate and ideal platform for investigating underlying molecular mechanisms of T2DM. This study reveals abnormal bile acid and arachidonic acid metabolism in T2DM hamsters, which may provide insights for studying the relationship between candidate proteins and KEGG pathways to elucidate the underlying molecular mechanism associated with T2DM.

Keywords: Arachidonic acid; Bile acid; Chinese hamster; Liver; TMT quantitative proteomics; Type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acid
  • Bile Acids and Salts
  • Cricetinae
  • Cricetulus
  • Diabetes Mellitus, Type 2*
  • Humans
  • Liver
  • Prostaglandin-E Synthases
  • Proteomics

Substances

  • Bile Acids and Salts
  • Arachidonic Acid
  • PTGES2 protein, human
  • Prostaglandin-E Synthases