TABLE 3.
Effects of dietary sphingomyelin and its metabolites on human physiology and chronic metabolic diseases.
| Metabolic disorders | SM and its’ metabolites | Model | Treatment and duration | Results | References |
| Normal physiology | SLs from ox braina | ExHC rats | 0.5 and 2% (wt/wt) SLs for 2 weeks |
c↓ Serum TG and liver CE levels; ↑ serum SM and liver PLs levels — Liver TG and serum CE levels |
(116) |
| SLs from bovine brainb | Donryu rats at 4 weeks old | 1% (wt/wt) SLs during two generations | ↓ Plasma TC levels; ↑ liver TG levels — Liver TC and plasma TG levels, tissue SLs and PLs levels |
(117) | |
| Milk SM | SD rat | 6.5–25 μmol/L 3H-SM and 14C-cholesterol for 4 h | ↓ Cholesterol absorption | (118) | |
| Milk SM | Caco-2 cells C57L/J mice at 7 weeks old |
2% (wt/wt) SM for 4 days | ↓ Uptake and esterification of cholesterol in Caco-2 cells ↓ Cholesterol absorption in mice |
(119) | |
| Egg yolk SM | SD rat at 8 weeks old | 5 or 10 μmol/h SM and 14C-cholesterol for 8 h | ↓ Lymphatic absorption of cholesterol, α-tocopherol and fatty acid in a dose dependent manner | (120) | |
| Milk SM and egg yolk SM | SD rat at 8 weeks old | 80 μmol/h SM and 14C-cholesterol for 8 h | ↓ Lymphatic absorption of cholesterol, fat, and other lipids Milk SM is more is more effective in inhibiting cholesterol absorption than egg SM |
(121) | |
| Egg yolk SM | Caco-2 monolayer | 0.6 mmol/L and 3H-cholesterol for 2 h | ↓ Cholesterol transport in a dose dependent manner alter the physicochemical properties of mixed micelles ↓ NPC1L1, Caveolin 1, SREBP-1/2 mRNA expression |
(122) | |
| Milk SM | Ten healthy adult males and females (ages 18–45) | a randomized crossover study with 4-week washout period 1 g/day milk SM for 14 days |
— Serum TG, TC, non-HDL cholesterol levels — Cholesterol absorption and cholesterol fractional synthesis rate — Intraluminal cholesterol solubilization ↑ HDL cholesterol levels |
(123) | |
| So | Caco-2 and HT-29-D4 cells | 0–50 μmol/L So and 3H-cholesterol for 4 h | ↓ Cholesterol uptake in a dose dependent manner ↓ NPC1L1 mRNA expression |
(125) | |
| Obesity | Chicken skin SM | Zucker rats fed with HFD at 6 weeks old | 0.5 and 2% (wt/wt) SM for 45 days | ↓ Hepatic lipid, plasma TC and insulin levels ↑ Adipor2, PPARR and Pdk4 mRNA and ↓Scd1 mRNA |
(133) |
| Egg yolk SM | C57BL/6 mice fed with HFD | 0.3, 0.6, or 1.2% SM (wt/wt) with high-fat diet for 4 weeks | ↓ Intestinal cholesterol absorption ↓ Total liver lipids (TC, TG) via the LXR-SREBP-1c pathway ↑ Fecal lipid and cholesterol output |
(28) | |
| Milk SM Egg yolk SM |
C57BL/6 mice fed with HFD at 8 weeks old | 0.1% (wt/wt) milk or egg yolk SM for 10 weeks | ↓ Body weight, serum TC, fasting glucose and liver TC, TG levels ↓ PPARγ-related mRNA expression (Scd1, Pparg2, Cd36, Fabp4, Ccl2) ↓ Epididymal adipose tissue inflammation and skeletal muscle lipid accumulation |
(134) | |
| Milk SM Egg yolk SM |
C57BL/6 mice fed with HFD at 8 weeks old | 0.25% (wt/wt) milk or egg yolk SM for 4 weeks | ↓ Body weight, serum TC, and liver TG via lipid absorption and metabolism regulation ↓ Serum LPS via bifidogenic effects and alterations in distal gut microbiota |
(129) | |
| MPL with 25% SM | C57BL/6 mice fed with HFD at 8 weeks old | 1.1 or 1.6% (wt/wt) MPL for 8 weeks | ↓ Body weight gain – Plasma markers of inflammation 1.6% (wt/wt) MPL: ↓ hepatic gene expression of macrophage marker F4/80 and ↑ Bifidobacterium animalis in cecal microbiota 1.1% (wt/wt) MPL: ↓ Lactobacillus reuteri in cecal microbiota |
(135) | |
| Milk SM and Cer | KK-Ay mice at 3 weeks old | 1.7% (wt/wt) of LC-BS (0.13% SM; 0.18% Cer) or 0.5% (wt/wt) Cer-fraction (0.34% Cer) or 0.5% (wt/wt) SM-fraction (0.25% SM) for 4 weeks | LC-BS: ↓ plasma TC and LDL cholesterol and liver TG levels Cer-fraction: ↓ liver TC and TG levels ↓ Stearoyl-CoA desaturase-1 SM-fraction: –plasma and liver lipids |
(136) | |
| Diabetes | S1P | HIT-T 15 cells pancreatic islets from ICR mouse at 8 weeks old |
10 μmol/L S1P | ↑ Insulin secretion from isolated mouse islets ↓ Intracellular cyclic AMP levels in a dose dependent manner |
(139) |
| S1P | INS-1 cells pancreatic islets from SD rats |
100–400 nmol/L S1P or dihydro-S1P for 4.5–5 h | ↓ TUNEL analysis and caspase-3 activity ↑ PKC activity ↓ Cytochrome c release ↓ Nitric oxide synthase |
(140) | |
| Milk SM | Obese/diabetic KK-Ay mice at 4 weeks old | 1% (wt/wt) milk SM for 4 weeks | ↓ Serum TC, non-HDL cholesterol, PLs and LDL-cholesterol levels; liver TG, TC, neutral and total lipids levels – Serum neutral lipids and cholesterol levels ↑ Fecal lipids (total lipids, TC, total bile acid and PLs) ↑ SREBP-2, HMG-CoA, and Cyp7a1 mRNA expression ↓ Scd1, Elovl2, Elovl5, Fads2 mRNA expression |
(29) | |
| Sea cucumber Cer and GlcCer | SD rat fed with high-fructose-diet | 0.16 g/kg Cer and 0.21 g/kg GlcCer of diet for 6 weeks | ↓ Serum glucose levels and glycosylated hemoglobin ↓ Hypertension Cer ↑ glycogen levels, glycogen synthesis and insulin signal transduction in skeletal muscle GlcCer ↑ hepatic glycogen levels, glycogen synthesis and insulin signal transduction attenuated inflammation in adipose tissue |
(141) | |
| CVDs | Egg yolk SM | C57BL/6 mice fed with HFD at 4 weeks old | 0.3, 0.6, or 1.2% (wt/wt) egg yolk SM for 4 weeks | ↓ Serum TMAO level – Serum choline and betaine levels |
(30) |
| apoE–/– mice fed with HFD at 5 weeks old | 1.2% (wt/wt) egg yolk SM for 16 weeks | ↑ Body weight – Aortic lesions – Serum lipid levels (TC, TG, non-esterified fatty acid and SM) |
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| apoE–/– mice at 5 weeks old | 1.2% (wt/wt) egg yolk SM for 19 weeks | ↓ Aortic lesion area in the aortic arch ↓ Lesion composition – Serum lipid, TMAO, choline and betaine levels |
|||
| Egg yolk SM | apoE–/– mice fed with HFD at 6 weeks old | 0.1% (wt/wt) egg yolk SM for 8 weeks | ↓ Epididymal fat mass, alanine aminotransferase (ALT) activity ↓ Aortic root lipid accumulation ↑ Spleen weights – Serum TG, TC, HDL cholesterol, non-HDL cholesterol and non-esterified fatty acid levels |
(128) | |
| Milk PLs | LDLr–/– mice fed with AMF-rich diet at 6 weeks old | 0.2%, 0.4% (wt/wt) milk SM for 14 weeks | ↓ Serum TG, TC, HDL cholesterol, non-HDL cholesterol and non-esterified fatty acid levels – Serum HDL-C, TG, liver enzymes, insulin, glucose, TNF-α, IL-1β, adiponectin, and resistin ↓ Inflammatory markers in the serum, liver, adipose and aorta ↓ Atherosclerosis development in both the thoracic aorta and the aortic root ↑ Relative abundance of Bacteroidetes, Actinobacteria, and Bifidobacterium, and ↓ Firmicutes in cecal feces |
(31) | |
| Milk PLs | Fifty-eight overweight postmenopausal women (ages 56–62) | Multi-center double-blind randomized trial with 4–6 weeks washout period 0, 3, or 5 g of milk PLs for 4 weeks |
↓ Blood lipids and associated cardiometabolic risk markers (TC/HDL cholesterol, apoB/apoA1) ↑ Fecal loss of coprostanol – Major bacterial populations and fecal short-chain fatty acids ↓ Cholesterol absorption but ↑ cholesterol-ileal efflux |
(32) | |
| Milk PLs | Fifty-eight overweight postmenopausal women (ages 56–62) | Multi-center double-blind randomized trial with 4–6 weeks washout period 0, 3, or 5 g of milk PLs for 4 weeks |
↓ Serum TC, LDL cholesterol and apoB levels ↓ Serum atherogenic C24:1 Cer, C16:1 SM, and C18:1 SM species ↓ Chylomicron content in total SM and C24:1 Cer, but ↑ total Cer in feces |
(148) |
aSphingolipids contained 68.2% ceramide-monosaccharide, 27.8% sphingomyelin, 2.9% cholesterol. bSphingolipids contained 64.8 % cerebroside and cerebroside sulfate, 29.0% sphingomyelin and 5.4% cholesterol and free fatty acids. c↓ refers the significantly decreasing index, ↑ refers the significantly increasing index, and – refers no significant changes. SM, sphingomyelin; SLs, sphingolipids; ExHC, exogenous hypercholesterolemic; TG, triglyceride; CE, cholesterol esters; TC, total cholesterol; SD rat, Sprague-Dawley rat; So, sphingosine; NPC1L1, Niemann-Pick-Like Protein 1; SREBP-1/2, sterol regulatory element-binding transcription factor 1/2; HFD, high-fat diet; Adipor2, adiponectin receptor 2; PPARγ, peroxisome proliferator activated receptor alpha; Pdk4, pyruvate dehydrogenase kinase 4; Scd1, stearoyl CoA desaturase; LPS, lipopolysaccharide; MPL, milk polar lipids; LC-BS, lipid-concentrated butter serum; S1P, sphingosine-1-phosphate; PLs, phospholipids; SREBP-2, sterol regulatory element-binding protein-2; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A reductase; Cyp7a1, cholesterol 7α-hydroxylase; Elovl2, elongases of very long chain fatty acids 2; Fads2, fatty acyl desaturase 2; Cer, ceramide; GlcCer, glucosylceramide; TMAO, trimethylamine N-oxide; ALT, alanine aminotransferase; LDLr, LDL receptor; AMF, anhydrous milk fat.