Role of circulating sphingolipids in lipid metabolism: Why dietary lipids matter

Abstract

Sphingolipids are structural components of cell membranes and lipoproteins but also act as signaling molecules in many pathophysiological processes. Although sphingolipids comprise a small part of the plasma lipidome, some plasma sphingolipids are recognized as implicated in the development of metabolic diseases and cardiovascular diseases. Plasma sphingolipids are mostly carried out into lipoproteins and may modulate their functional properties. Lipids ingested from the diet contribute to the plasma lipid pool besides lipids produced by the liver and released from the adipose tissue. Depending on their source, quality and quantity, dietary lipids may modulate sphingolipids both in plasma and lipoproteins. A few human dietary intervention studies investigated the impact of dietary lipids on circulating sphingolipids and lipid-related cardiovascular risk markers. On the one hand, dietary saturated fatty acids, mainly palmitic acid, may increase ceramide concentrations in plasma, triglyceride-rich lipoproteins and HDL. On the other hand, milk polar lipids may decrease some molecular species of sphingomyelins and ceramides in plasma and intestine-derived chylomicrons. Altogether, different dietary fatty acids and lipid species can modulate circulating sphingolipids vehicled by postprandial lipoproteins, which should be part of future nutritional strategies for prevention of cardiovascular diseases.

Keywords: ceramide; dietary lipids; nutrition; postprandial metabolism; sphingolipids; sphingomyelin.

Figure 1

Schematic overview of postprandial intestinal metabolism of dietary lipids, especially sphingolipids. Following ingestion of dietary fats, triglycerides (TG) including saturated fatty acids (SFA) are digested in the intestinal lumen by pancreatic lipases into 2-monoacylglycerols and unesterified fatty acids (FA) (e.g., palmitic acid), which are then absorbed in the enterocytes, resynthesized as TG and packaged into chylomicrons (CM) for secretion into lymph. In the enterocyte, condensation of palmitoyl-CoA and serine by serine palmitoyltransferase (SPT) produces dihydroceramide (dihydroCer) and Cer. Among milk polar lipids including sphingolipids, sphingomyelin (SM) is hydrolyzed by an alkaline sphingomyelinase to ceramide (Cer) and phosphocholine. Cer is further hydrolyzed by a neutral ceramidase into sphingosine (SPH) and FA. In the enterocyte, SPH is mainly converted to palmitic acid, which is incorporated into TG but may be reincorporated into Cer and complex sphingolipids. Intestine-derived lipoproteins, i.e., CM, the major triglyceride-rich lipoproteins (TGRL) and HDL, are released into the bloodstream via the lymph. As described in the present review, SFA consumption may lead to increased concentrations of Cer in TGRL (28) and HDL (33). Supplementation with milk polar lipids may result in decreased concentrations of SM and Cer in CM (27). Future research should study the endogenous metabolism of sphingolipid species in enterocytes. Some figure elements were obtained from Servier Medical Art (https://smart.servier.com/).