Alterations in myocardial cardiolipin content and composition occur at the very earliest stages of diabetes: A shotgun lipidomics study

Xianlin Han, Jingyue Yang, Kui Yang, Zhao Zhongdan, Dana R. Abendschein, Richard W. Gross

Research output: Contribution to journalArticlepeer-review

182 Scopus citations

Abstract

Recently, we have identified the dramatic depletion of cardiolipin (CL) in diabetic myocardium 6 weeks after streptozotocin (STZ) injection that was accompanied by increases in triacylglycerol content and multiple changes in polar lipid molecular species. However, after 6 weeks in the diabetic state, the predominant lipid hallmarks of diabetic cardiomyopathy were each present concomitantly, and thus, it was impossible to identify the temporal course of lipid alterations in diabetic myocardium. Using the newly developed enhanced shotgun lipidomics approach, we demonstrated the dramatic loss of abundant CL molecular species in STZ-treated hearts at the very earliest stages of diabetes accompanied by a profound remodeling of the remaining CL molecular species including a 16-fold increase in the content of 18:2-22:6-22:6-22:6 CL. These alterations in CL metabolism occur within days after the induction of the diabetic state and precede the triacylglycerol accumulation manifest in diabetic myocardium. Similarly, in ob/ob mice, a dramatic and progressive redistribution from 18:2 FA-containing CL molecular species to 22:6 FA-containing CL molecular species was also identified. Collectively, these results demonstrate alterations in CL hydrolysis and remodeling at the earliest stages of diabetes and are consistent with a role for alterations in CL content in precipitating mitochondrial dysfunction in diabetic cardiomyopathy.

Original languageEnglish (US)
Pages (from-to)6417-6428
Number of pages12
JournalBiochemistry
Volume46
Issue number21
DOIs
StatePublished - May 29 2007

ASJC Scopus subject areas

  • Biochemistry

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