Dietary and Endogenous Sphingolipid Metabolism in Chronic Inflammation

Abstract

Chronic inflammation is a common underlying factor in many major metabolic diseases afflicting Western societies. Sphingolipid metabolism is pivotal in the regulation of inflammatory signaling pathways. The regulation of sphingolipid metabolism is in turn influenced by inflammatory pathways. In this review, we provide an overview of sphingolipid metabolism in mammalian cells, including a description of sphingolipid structure, biosynthesis, turnover, and role in inflammatory signaling. Sphingolipid metabolites play distinct and complex roles in inflammatory signaling and will be discussed. We also review studies examining dietary sphingolipids and inflammation, derived from in vitro and rodent models, as well as human clinical trials. Dietary sphingolipids appear to influence inflammation-related chronic diseases through inhibiting intestinal lipid absorption, altering gut microbiota, activation of anti-inflammatory nuclear receptors, and neutralizing responses to inflammatory stimuli. The anti-inflammatory effects observed with consuming dietary sphingolipids are in contrast to the observation that most cellular sphingolipids play roles in augmenting inflammatory signaling. The relationship between dietary sphingolipids and low-grade chronic inflammation in metabolic disorders is complex and appears to depend on sphingolipid structure, digestion, and metabolic state of the organism. Further research is necessary to confirm the reported anti-inflammatory effects of dietary sphingolipids and delineate their impacts on endogenous sphingolipid metabolism.

Milk Polar Lipids: Underappreciated Lipids with Emerging Health Benefits

“…Sphingomyelin (or ceramide phosphocholine) is an amphipathic sphingolipid in which a phosphorylcholine head group is linked to ceramide [15]. In glucosylceramide (GluCer), the 1-position of ceramide is linked to a glucose residue, whereas in lactosylceramide (LacCer), it is linked to lactose [8,16].…”

“…SM content encompasses approximately 25% of total milk polar lipids, and SM is found at~3:1 ratio to cholesterol by mass [6]. While health effects of PLs from eggs [7] and SLs [8] have been reviewed previously, the health effects of consuming milk polar lipids have not been reviewed extensively. Since the SLs found within MFGM are known to impact various aspects of lipid metabolism [9,10], gut microbiota [10], and inflammation [9,11], milk polar lipids may be considered as food matrix factors that may confer health benefits and/or impact effects of other dietary lipids, with implications for full-fat vs. lower-fat dairy varieties.…”

Dietary choline is related to increased risk of acute myocardial infarction in patients with stable angina pectoris

“…Also, dietary choline intake has been associated with lower inflammation markers such as CRP, 268 interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in a cross sectional study 269 23 involving healthy participants [46]. Pre-clinical studies showed potential anti-inflammatory 270 effects of sphingolipids (with SM as main contributor) but the limited number of human studies 271 and the use of complex phospholipid mixtures instead of single phospholipids, make it difficult 272 to conclude on the effects of sphingolipids on inflammation [47]. In the present study, we did 273 not observe any association between dietary choline and CRP.…”

Dietary Cholesterol, Serum Lipids, and Heart Disease: Are Eggs Working for or Against You?

“…These findings suggest that dietary SM may work via effects on gut microbiota, which is supported by a recent mouse study showing dietary SM altered gut microbiota in high fat diet-fed mice [ 84 ]. More research is warranted to better understand the effects of dietary SM on chronic disease progression, including determining whether such effects are solely dependent on inhibiting lipid absorption or due to other reported effects on gut microbiota and inflammation [ 85 ].…”