Hypercaloric diets lead to the dysregulation of multiple lipid metabolic pathways, which contributes to the onset and progression of metabolic disease
Lipidomic studies are starting to decipher the dysregulation of lipid metabolism associated with metabolic disease
Lipid metabolic pathways represent potential therapeutic targets to prevent or delay the onset and progression of metabolic disease
Further animal studies and clinical trials are required to define the stage of disease at which modulation of lipid metabolism will have maximal efficacy
Whether intervention into a single metabolic pathway or multiple pathways will produce optimal results remains to be determined
Obesity, insulin resistance, type 2 diabetes mellitus and cardiovascular disease form a metabolic disease continuum that has seen a dramatic increase in prevalence in developed and developing countries over the past two decades. Dyslipidaemia resulting from hypercaloric diets is a major contributor to the pathogenesis of metabolic disease, and lipid-lowering therapies are the main therapeutic option for this group of disorders. However, the fact that dysfunctional lipid metabolism extends far beyond cholesterol and triglycerides is becoming increasingly clear. Lipidomic studies and mouse models are helping to explain the complex interactions between diet, lipid metabolism and metabolic disease. These studies are not only improving our understanding of this complex biology, but are also identifying potential therapeutic avenues to combat this growing epidemic. This Review examines what is currently known about phospholipid and sphingolipid metabolism in the setting of obesity and how metabolic pathways are being modulated for therapeutic effect.
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P.J.M. is supported by a Senior Research Fellowship from the National Health and Medical Research Council of Australia.
P.J.M. declares no competing interests. S.A.S. is co-founder and scientific adviser of Centaurus Therapeutics Inc.
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Meikle, P., Summers, S. Sphingolipids and phospholipids in insulin resistance and related metabolic disorders. Nat Rev Endocrinol 13, 79–91 (2017). https://doi.org/10.1038/nrendo.2016.169
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