Dietary Sphingolipids Contribute to Health Via Intestinal Maintenance
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International Journal of Molecular Sciences Review Dietary Sphingolipids Contribute to Health via Intestinal Maintenance Shinji Yamashita 1, Mikio Kinoshita 1,* and Teruo Miyazawa 2 1 Department of Life and Food Sciences, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan; [email protected] 2 Food and Biotechnology Platform Promoting Project, New Industry Creation Hatchery Center (NICHe), Tohoku University, Sendai 980-8579, Japan; [email protected] * Correspondence: [email protected]; Tel.: +81-155-49-5545 Abstract: As sphingolipids are constituents of the cell and vacuole membranes of eukaryotic cells, they are a critical component acquired from our daily diets. In the present review, we highlight the knowledge regarding how dietary sphingolipids affect our health, particularly our intestinal health. Animal- and plant-derived foods contain, respectively, sphingomyelin (SM) and glucosylce- ramide (GlcCer) as their representative sphingolipids, and the sphingoid base as a specific structure of sphingolipids also differs depending upon the source and class. For example, sphingosine is predominant among animal sphingolipids, and tri-hydroxy bases are present in free ceramide (Cer) from plants and fungi. Dietary sphingolipids exhibit low absorption ratios; however, they possess various functions. GlcCer facilitates improvements in intestinal impairments, lipid metabolisms, and skin disorders, and SM can exert both similar and different effects compared to those elicited by GlcCer. We discuss the digestion, absorption, metabolism, and function of sphingolipids while focused on the structure. Additionally, we also review old and new classes in the context of current advancements in analytical instruments. Citation: Yamashita, S.; Kinoshita, M.; Miyazawa, T. Dietary Keywords: ceramide; glucosylceramide; inflammation; intestine; sphingomyelin; sphingosine Sphingolipids Contribute to Health via Intestinal Maintenance. Int. J. Mol. Sci. 2021, 22, 7052. https://doi.org/ 10.3390/ijms22137052 1. Introduction The intestine digests food materials and absorbs nutrients and water and is also Academic Editor: Paola Giussani deeply implicated in human health maintenance via the immune and nervous systems [1]. However, intestinal impairments, such as colon cancer and inflammatory bowel disease Received: 15 June 2021 (IBD), are becoming increasingly problematic pathologies that affect both sexes world- Accepted: 26 June 2021 wide. Despite advances in the diagnosis and treatment of these diseases, their incidence Published: 30 June 2021 rates have steadily increased in East Asian countries, including Japan, and their incidence rates in Western countries also remain high [2,3]. Epidemiological studies indicate that Publisher’s Note: MDPI stays neutral intestinal impairments are strongly associated with diet [4], and dietary compounds di- with regard to jurisdictional claims in published maps and institutional affil- rectly interact with the colonic epithelium cells and may affect growth, differentiation, iations. and cell death within the tissue [5]. Endogenous sphingolipids are known to play key roles in inflammation-related diseases, including intestinal impairment [6,7]. Although dietary sphingolipids are also believed to be implicated in these diseases, food-derived sphingolipids differ from endogenous sphingolipids in regard to their different structures among plants, fungi, and invertebrates and their differing routes into the body, which can Copyright: © 2021 by the authors. include digestion and absorption [8]. In this review, we introduce sphingolipids as foods Licensee MDPI, Basel, Switzerland. or supplements that can facilitate various functions, such as influencing intestinal health, This article is an open access article distributed under the terms and and we focus primarily on sphingolipid structure in this context. conditions of the Creative Commons 2. Diversity of Sphingolipid Classes and Base Composition in Foods Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ Sphingolipids are primarily located within the cell and vacuole membranes of most 4.0/). eukaryotes and some prokaryotes, and, based on this, we consume sphingolipids daily in Int. J. Mol. Sci. 2021, 22, 7052. https://doi.org/10.3390/ijms22137052 https://www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2021, 22, x FOR PEER REVIEW 2 of 19 Int. J. Mol. Sci. 2021, 22, 7052 2. Diversity of Sphingolipid Classes and Base Composition in Foods 2 of 18 Sphingolipids are primarily located within the cell and vacuole membranes of most eukaryotes and some prokaryotes, and, based on this, we consume sphingolipids daily in our diets. S Sphingolipidsphingolipids present in most foods primarily exist as complexcomplex sphingolipidssphingolipids thatthat areare composedcomposed of of a sphingoida sphingoid base base (SB) with(SB) anwith amide-linked an amide fatty-linked acid fatty (i.e., acid ceramide, (i.e., ceramide,Cer) and aCer) polar and head a polar group, head rather group than, rather a free than Cer a [ 8free]. Throughout Cer [8]. Throughout nature, there nature, are therediverse are compositions diverse compositions of sphingolipid of sphingolipid classes and classes sphingoid and sphingoid bases (Figure bases1). (Figure 1). Figure 1. Structures of sphingolipids and diversity of sphingoid bases depend on food sources. Abbreviations: C, carbon number; c, cis; d, dihydroxy; h,h, α-hydroxy;-hydroxy; Me, methyl;methyl; tt,, transtrans;; t,t, trihydroxy.trihydroxy. SSphingolipidsphingolipids are typically classified as neutralneutral andand acidicacidic sphingolipids.sphingolipids. Neutral sphingolipid classes in animal-derived foods such as meats and egg yolk primarily con- sphingolipid classes in animal-derived foods such as meats and egg yolk primarily con- sist of sphingomyelin (SM; a phosphocholine as the polar head group) and also include sist of sphingomyelin (SM; a phosphocholine as the polar head group) and also include glucosylceramide (GlcCer; a glucose) and Cer, while the acidic sphingolipid classes are glucosylceramide (GlcCer; a glucose) and Cer, while the acidic sphingolipid classes are gangliosides that contain more than one sialic acid within the sugar chain [9,10]. Milk and gangliosides that contain more than one sialic acid within the sugar chain [9,10]. Milk dairy products contain GlcCer and lactosylceramide (LacCer) in addition to SM, and they and dairy products contain GlcCer and lactosylceramide (LacCer) in addition to SM, and are rich in gangliosides [10,11]. The sphingolipid composition of offal (variety meats, e.g., they are rich in gangliosides [10,11]. The sphingolipid composition of offal (variety brain, spinal cord, liver, and intestine) is unique. For example, the brain and spinal cord, meats, e.g., brain, spinal cord, liver, and intestine) is unique. For example, the brain and both of which are abundant in sphingolipids, contain large amounts of galactocylceramide spinal cord, both of which are abundant in sphingolipids, contain large amounts of (GalCer) and sulfatides that are represented by GalCer 3-sulfate. The neutral sphingolipids galactocylceramide (GalCer) and sulfatides that are represented by GalCer 3-sulfate. The from fish-derived foods are primarily SM and monoglycosylceramides (e.g., GalCer and nGlcCer)eutral sphingolipids [12,13], while from foods fish from-derived invertebrates foods are such primarily as Mollusca SM and contain monoglycosylcer- Cer phospho- amidesethanolamine (e.g., GalCer and Cer and 2-aminoethylphosphonate GlcCer) [12,13], while foods (CAEP) from instead invertebrates of SM [14 such]. The as polarMol- luscahead groupcontain of Cer CAEP phosphoethanolamine possesses a C-P bond thatand consistsCer 2-aminoethylphosphonate of a phosphorus atom that (CAEP) is directly in- steadbound of to SM a carbon [14]. The atom. polar In contrast,head group neutral of CAEP sphingolipid possesses classes a C-P present bond that in foods consists derived of a from plants are primary composed of GlcCer and Cer, and rice and wheat grains contain small amounts of oligo-glycosyl Cer that possess sugar chains that are composed of glucose and mannose [15]. Plant acidic sphingolipids comprise inositol phosphoceramide (IPC) and glycosyl IPC (GIPC), both of which are markedly more abundant than is GlcCer [16]. Foods Int. J. Mol. Sci. 2021, 22, 7052 3 of 18 derived from fungi such as mold and mushrooms possess GlcCer, GalCer, and LacCer as neutral classes and IPC and GIPC as acidic classes [17]. Although general eukaryotes can possess higher or lower levels of GlcCer, yeasts (Saccharomyces cerevisiae) used for panary fermentation and sake brewing do not contain GlcCer, while yeasts contain Cer, IPC, and GIPC [18]. Additionally, sphingolipids do not exist in general prokaryotes, but Cer and the specific derivatives, such as Cer glucuronide, are present in certain prokaryotes, including acetic acid bacteria (Acetobacter)[19–21]. Fermented foods such as sake lees, a by-product of sake (rice wine) brewing, contain markedly high levels of free Cer and free SBs [22,23]. In regard to animal sphingoid bases, trans-4-sphingenine (sphingosine, d18:14t) is the most prevalent, and sphinganine (d18:0) and 4-hydroxysphinganine (phytosphingosine, t18:0) also occur frequently in small amounts (Table1). However, the small intestine, kidney, and skin, which exhibit C4-hydroxylase activity, are abundant in t18:0 [24]. Plant sphin- golipids exhibit a highly diverse SB composition due to having