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Abstract

Cardiac myocyte membranes contain lipids which remodel dramatically in response to heart growth and remodeling. Lipid species have both structural and functional roles. Physiological and pathological cardiac remodeling have very distinct phenotypes, and the identification of molecular differences represent avenues for therapeutic interventions. Whether the abundance of specific lipid classes is different in physiological and pathological models was largely unknown. The aim of this study was to determine whether distinct lipids are regulated in settings of physiological and pathological remodeling, and if so, whether modulation of differentially regulated lipids could modulate heart size and function. Lipidomic profiling was performed on cardiac-specific transgenic mice with 1) physiological cardiac hypertrophy due to increased Insulin-like Growth Factor 1 (IGF1) receptor or Phosphoinositide 3-Kinase (PI3K) signaling, 2) small hearts due to depressed PI3K signaling (dnPI3K), and 3) failing hearts due to dilated cardiomyopathy (DCM). In hearts of dnPI3K and DCM mice, several phospholipids (plasmalogens) were decreased and sphingolipids increased compared to mice with physiological hypertrophy. To assess whether restoration of plasmalogens could restore heart size or cardiac function, dnPI3K and DCM mice were administered batyl alcohol (BA; precursor to plasmalogen biosynthesis) in the diet for 16 weeks. BA supplementation increased a major plasmalogen species (p18:0) in the heart but had no effect on heart size or function. This may be due to the concurrent reduction in other plasmalogen species (p16:0 and p18:1) with BA. Here we show that lipid species are differentially regulated in settings of physiological and pathological remodeling. Restoration of lipid species in the failing heart warrants further examination.

Item Type:	Article
Authors/Creators:	Tham, YK and Huynh, K and Mellett, NA and Henstridge, DC and Kiriazis, H and Ooi, JYY and Matsumoto, A and Patterson, NL and Sadoshima, J and Meikle, PJ and McMullen, JR
Keywords:	dietary supplement, heart failure, lipids, physiological cardiac hypertrophy, plasmalogens, atrial natriuretic factor, batyl alcohol, brain natriuretic peptide, collagen type 1, connective tissue growth factor, glycerol derivative, plasmalogen, male
Journal or Publication Title:	Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Publisher:	Elsevier Science Bv
ISSN:	1388-1981
DOI / ID Number:	https://doi.org/10.1016/j.bbalip.2017.12.003
Copyright Information:	Copyright 2017 Elsevier B.V.
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