Lipidomic analysis reveals significant lipogenesis and accumulation of lipotoxic components in ob/ob mouse organs

Jun Hayakawa, Miao Wang, Chunyan Wang, Rowland H. Han, Zhen Y. Jiang, Xianlin Han

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

To further understand the role of lipogenesis and lipotoxicity in the development of obesity and diabetes, lipidomes of various organs from ob/ob mice and their wild type controls were analyzed by shotgun lipidomics at 10, 12, and 16 weeks of age. We observed that the amounts of fatty acyl (FA) chains corresponding to those from de novo synthesis (e.g., 16:0, 16:1, and 18:1 FA) were substantially elevated in ob/ob mice, consistent with increased expression of genes and proteins involved in biosynthesis. Polyunsaturated fatty acid species were moderately increased in the examined tissues of ob/ob mice, since they can only be absorbed from diets or elongated from the ingested n-3 or n-6 FA. Different profiles of FA chains between ob/ob mouse liver and skeletal muscle reflect diverging lipogenesis pathways in these organs. Amounts of vaccenic acids (i.e., 18:1(n-7) FA) in 12- and 16-week ob/ob mouse liver were significantly increased compared to their controls, indicating enhanced de novo synthesis of this acid through 16:1(n-7) FA in the liver starting at 12 weeks of age. Coincidentally, synthesis of triacylglycerol from monoacylglycerol in the liver was also increased in ob/ob mice starting at 12 weeks of age, as revealed by simulation of triacylglycerol synthesis. Moreover, levels of lipotoxic lipid classes were significantly higher in ob/ob mice than their age-matched controls, supporting the notion that elevated lipotoxic components are tightly associated with insulin resistance in ob/ob mice. Taken together, the current study revealed that lipogenesis and lipotoxicity in ob/ob mice likely contribute to insulin resistance and provides great insights into the underlying mechanisms of diabetes and obesity.

Original languageEnglish (US)
Pages (from-to)161-169
Number of pages9
JournalProstaglandins Leukotrienes and Essential Fatty Acids
Volume136
DOIs
StatePublished - Sep 2018

Keywords

  • Lipidomics
  • Lipogenesis
  • Lipotoxicity
  • Obesity
  • Shotgun lipidomics
  • ob/ob Mice

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology

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