Table 2.
Animal studies examining the effects of dietary sphingolipids on inflammation.
| Sphingolipid Source | Animal Model | Diet and Duration | Results | Ref |
|---|---|---|---|---|
| Sphingomyelin | Male JcI:ICR mice ( n = 10/group) | Mice were acclimated to AIN-76 diet for 3 days before the addition of 0.1% SM ( wt/wt; unspecified source). Three days following SM in diet, 2% DSS added to drinking water for 1 week | SM: ↓weight of intestine, disease activity score, intestinal MPO activity, weight loss, histological damage of the mucosa, ↑IgA in large intestine without DSS treatment | Furuya et al. 2008 [180] |
| Sphingomyelin | Male and female epithelial and hematopoietic cell specific PPARγ−/− mice (MMTV-LTR-promoter) ( n = 10/group) | AIN-76A diets ± 0.1% ( wt/wt) milk SM (MSM) with 7 days of diet. Day 8: Injection of azoxymethane (10 mg/kg). Day 13: 2% DSS added to drinking water | PPARγ+/+ Mice: MSM: ↓ recovery time from DSS, ↑ mRNA of pro- and anti- inflammatory genes | Mazzei et al. 2011 [12] |
| PPARγ−/− Mice: MSM: ↓recovery time from DSS, ↑survival, ↑mRNA of pro- and anti- inflammatory genes | ||||
| Sphingomyelin | C57BL/6J mice (
n = 17/group); IL-10−/− mice (n = 5/group) |
Colitis was induced in C57BL/6J mice using 0.2% DSS in drinking water.
IL-10−/− develop spontaneous colitis. Mice were gavaged with either water, 4 mg, or 8 mg egg-derived SM (ESM) suspended in water |
4 mg ESM C57BL/6: ↑ intestinal epithelial cell ceramide, colitis score, weight loss, epithelial damage score, apoptotic cells, cathepsin D, caspase-3 activity | Fischbeck et al. 2011 [183] |
| 8 mg ESM C57BL/6: ↑sphingosine in IECs with no DSS, ↑SM in IECs with DSS treatment, ↔ colitis score, weight loss, epithelial damage score, apoptosis | ||||
| 4 mg ESM IL-10−/−: ↑ colitis score and weight loss | ||||
| Sphingomyelin | Male C57BL/6J mice ( n = 10/group) | Mice were fed HFD (45% kcal from fat) ± 0.25% ( wt/wt) egg- or milk-derived SM (ESM or MSM) for 4 week | MSM: ↓serum LPS, ↓fecal % Gram-negative bacteria, ↑fecal % Bifidobacterium, ↔ FITC-dextran gut permeability | Norris et al.. 2016 [10] |
| ESM: ↔ serum LPS | ||||
| Sphingomyelin | Male C57BL/6 mice ( n = 14) | Mice were fed HFD (60% kcal from fat; 0.15% cholesterol by weight) ± 0.1% ( wt/wt) egg- or milk-derived SM (ESM or MSM) for 10 week | MSM: ↓serum CCL2, ↓adipose inflammatory mRNA (F4/80, TNF-α) | Norris et al. 2017 [131] |
| ESM: ↓serum CCL2, ↓adipose crown-like structures, ↓adipose inflammatory mRNA (F4/80, CD68, CD11c, CCL2, TNF-α), ↓ hepatic CCL2 mRNA | ||||
| Glucosylceramide | Female BALB/c mice ( n = 10–20/group) | Mice were acclimated to AIN-76 test diet ± GluCer (0.1% wt/wt) for 10 days. Drinking water was supplemented with 0.2% DSS for 15 days | GluCer: ↓weight loss, ↓colonic MPO, TIMP-1, MIG, IP-10, IL-16, IL-1β, IL-1α, sICAM-1 | Arai et al. 2015 [182] |
| Glucosylceramide | Male BALB/c mice ( n = 8/group) | Mice fed AIN-76A diet ± 0.1% ( wt/wt) maize GluCer for 7 week with weekly IP injection of DMH | GluCer treatment: ↓aberrant crypt foci, ↓ colonic IP-10, I-TAC, MIG, RANTES, TNF-α, IL-23, M-CSF | Yamashita et al. 2017 [181] |
| Ganglioside | Male Sprague-Dawley rats ( n = 16/group) | Rats fed a 20% wt/wt HFD containing 0.1% ganglioside (GG) for 2 week before LPS IP injections (3 mg/kg) and samples collected 6 h later | GG: ↓ intestinal cholesterol, PAF, PGE2, LTB4, interleukin (IL)-1β, TNF-α and ↓ plasma LTB4, TNF-α, IL-1β, ↑ intestinal GG content | Park et al. 2007 [174] |
| Milk Fat Globule Membrane (MFGM) | Male BALB/c mice ( n = 6/group) | Mice fed AIN-76A or modified AIN-76A to include 12.5% MFGM for 5 week. Mice were IP injected with LPS (10 mg/kg) and gut leakiness and serum cytokines were measured at 24 and 48 h | MFGM 24 h: ↓ gut permeability to FITC-dextran ↓ IFNγ, CCL2, TNF-α, IL-3, IL-17, IL-12p70 compared to control diet at 24 h | Snow et al. 2011 [173] |
| MFGM 48 h: Similar to MFGM 24 h with RANTES, IL-5, and IL-1β compared to 24 h controls, as control mice did not survive 48 h | ||||
| Mixed Phospholipids | C57BL/6J mice ( n = 12/group) | Mice were fed 40% kcal from fat (mostly palm oil) for 8 week on one of three diets: HFD control, HFD-soy phospholipids (SPL), HFD-milk phospholipids (MPL) | MPL: ↑ Muc2 staining in colon, ↓ adipose CD68 mRNA compared, ↓ jejunal goblet cell count SPL: ↑ epididymal adipose MCP-1, TNF-α, LBP, leptin mRNA | Lecomte et al. 2015 [184] |
Abbreviations and symbols: CCL2, C-C motif chemokine ligand 2; DSS, dextran sulfate sodium; FITC, fluorescein isothiocyanate; GluCer, glucosylceramide; HFD, high fat diet; IECs, intestinal epithelial cells; IFNγ, interferon gamma; IgA, immunoglobulin A; IP, intraperitoneal; IP-10, interferon gamma-induced protein 10; ITAC, interferon-inducible T-cell alpha chemoattractant; LTB4, leukotriene B4; LPS, lipopolysaccharide; M-CSF, macrophage colony-stimulating factor; MFGM, milk fat globule membrane; MIG, monokine induced by gamma interferon; MPO, myeloperoxidase; PAF, platelet-activating factor; PGE2, prostaglandin E2; PPARγ, peroxisome proliferator-activated receptor gamma; RANTES, regulated on activation, normal T cell expressed and secreted; sICAM-1, soluble intercellular adhesion molecule 1; SM, sphingomyelin; TIMP-1, TIMP metallopeptidase inhibitor 1; TNF-α, tumor necrosis factor-alpha; ↑, increase; ↓ decrease; ↔ no change.