Abstract
Sphingolipid concentrations have been associated with risk of type 2 diabetes and cardiovascular diseases. Because sphingolipids can be synthesized de novo from saturated fatty acids (SFA), dietary fatty acids may affect plasma sphingolipid concentrations. We aimed to evaluate dietary fat and protein intakes in relation to circulating sphingolipid levels. We used cross-sectional data from 2860 ethnic Chinese Singaporeans collected from 2004–2007. Nutrient intakes were estimated on the basis of a validated 159-item food frequency questionnaire. We quantified 79 molecularly distinct sphingolipids in a large-scale lipidomic evaluation from plasma samples. Higher saturated fat intake was associated with higher concentrations of 16:1;O2 sphingolipids including ceramides, monohexosylcermides, dihexosylceramides, sphingomyelins, and sphingosine 1-phosphates. Higher polyunsaturated fat intake was associated with lower plasma long-chain ceramides and long-chain monohexosylcermide concentrations. Protein intake was inversely associated with concentrations of most subclasses of sphingolipids, with the exception of sphingolipids containing a 16:1;O2 sphingoid base. Lower intake of saturated fat and higher intake of polyunsaturated fat and protein may decrease plasma concentrations of several sphingolipid classes. These findings may represent a novel biological mechanism for the impact of nutrient intakes on cardio-metabolic health.
Highlights
Sphingolipids are a molecularly diverse type of lipid with a wide variety of biological functions in eukaryotic cells
Higher saturated fatty acids (SFA) intake was associated with higher concentrations of several classes of sphingolipids, with a 16:1;O2 backbone including ceramides, monohexosylceramide (HexCer), dihexosylceramide (Hex2Cer), SM, and sphingoid base phosphate (SPBP)
Higher polyunsaturated fatty acid (PUFA) intake was associated with lower long-chain ceramides and long-chain HexCer concentrations (Table 2)
Summary
Sphingolipids are a molecularly diverse type of lipid with a wide variety of biological functions in eukaryotic cells. They differ by head group structure, chain length, and unsaturation degree in the sphingoid backbone and fatty acyl chain. Sphingomyelin (SM) species were directly associated with risk of type 2 diabetes (T2D) [1] and cardiovascular diseases (CVDs) [2,3,4]. Ceramides may increase chronic disease risk by promoting inflammation [8,9,10]. Endogenous ceramides promoted low-density lipoprotein (LDL) uptake [11] and transcytosis of oxidized LDL [12], and both events may play a role in atherosclerosis. Ceramides and complex sphingolipids derived from ceramides, such as glucosylceramides (GluCers), may act as mediators of cell death induction [13] and promote T2D through inducing pancreatic beta-cell toxicity and apoptosis, resulting in dysfunctional insulin secretion [14,15]
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