Altered Colonic Mucosal Polyunsaturated Fatty Acid (PUFA) Derived Lipid Mediators in Ulcerative Colitis: New Insight into Relationship with Disease Activity and Pathophysiology

Abstract Objectives Assess the differences in triacylglycerol (TAG) and cholesterol ester (CE) species in the plasma of individuals displaying heterogeneous lipid responses following long chain n-3 (LCn-3) polyunsaturated fatty acid supplementation. Methods We performed a targeted, mass spectrometry (MS), infusion-based lipidomic analysis on plasma samples obtained from a clinical study in which participants were supplemented with 3 g/day of LCn-3 in the form of fish oil capsules over a 6-week period. Triacylglycerol (TAG) species and cholesteryl esters (CE) were quantified for 130 participants pre- and post-supplementation. Results Based on the change of total TAG concentrations following supplementation, participants were segregated into three response phenotypes: (1) positive responders (R+; TAG decrease < 10%), (2) non-responders (NR; TAG changes +/− 10%), and (3) negative responders (R−; TAG increase > 10%) representing 87/130 (67%), 24/130 (18%), and 19/130 (15%) of the study samples, respectively. There were no phenotypic differences for age, sex, body-mass index, glycemia, or ApoB concentrations. Sparse partial least squares discriminant analysis separated the three phenotypes with component 1 attributed to changes in TAG 50–53: X with 0–3 desaturations with R + having reductions in these TAG. Separation along component 2 identified lower mass TAG 46–48: X with 1–3 desaturations likely containing 14:0. This latter effect impacted mostly NR and R- phenotypes. Analysis of individual TAG species per response phenotype revealed TAG species that did not align with the overall TAG response phenotype. Using the TAG response phenotype for grouping, we performed SPLDA analysis for CE responses. We observed that distinction of the TAG response phenotypes qualitatively applies to CE in which separation along component 1 (65% of variance) was due to differences in CE 18:0, 18:1, and 14:0. CE 20:5 was elevated equally (>300%) between all phenotypes indicating LCn-3 intake. However, CE 22:6 was elevated R− (86%) to a greater extent vs. Res+ (55%) and NR (49%) phenotypes. Conclusions Our data identify lipidomic signatures (TAG and CE) associated with LCn-3 response phenotypes in humans and provide insight into the variability of lipid metabolism in humans. Funding Sources USDA-NIFA, USDA-ARS and CIHR MOP-229,488.

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Influence of cellular incorporation of Omega 3 and 6 polyunsaturated fatty acid on colonic cell restitution: A possible mechanism of clinical efficacy of eicosapentaenoic acid on ulcerative colitis

Gastroenterology ◽

10.1016/s0016-5085(03)81310-0 ◽

2003 ◽

Vol 124 (4) ◽

pp. A262

Author(s):

Morio Takahashi ◽

Ryoko Hanazawa ◽

Shinobu Kataoka ◽

Ryoichi Soma ◽

Hiroshi Takada ◽

...

Keyword(s):

Ulcerative Colitis ◽

Fatty Acid ◽

Eicosapentaenoic Acid ◽

Polyunsaturated Fatty Acid ◽

Clinical Efficacy ◽

Omega 3 ◽

Cellular Incorporation

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Adjunct n-3 Long-Chain Polyunsaturated Fatty Acid Treatment in Tuberculosis Reduces Inflammation and Improves Anemia of Infection More in C3HeB/FeJ Mice With Low n-3 Fatty Acid Status Than Sufficient n-3 Fatty Acid Status

Frontiers in Nutrition ◽

10.3389/fnut.2021.695452 ◽

2021 ◽

Vol 8 ◽

Author(s):

Frank E. A. Hayford ◽

Robin C. Dolman ◽

Mumin Ozturk ◽

Arista Nienaber ◽

Cristian Ricci ◽

...

Keyword(s):

Fatty Acid ◽

Polyunsaturated Fatty Acid ◽

Post Infection ◽

Lipid Mediators ◽

Chain Polyunsaturated Fatty Acid ◽

Lung Pathology ◽

Fatty Acid Status ◽

Populations At Risk ◽

Acid Status ◽

Long Chain

Populations at risk for tuberculosis (TB) may have a low n-3 polyunsaturated fatty acid (PUFA) status. Our research previously showed that post-infection supplementation of n-3 long-chain PUFA (LCPUFA) in TB without TB medication was beneficial in n-3 PUFA sufficient but not in low-status C3HeB/FeJ mice. In this study, we investigated the effect of n-3 LCPUFA adjunct to TB medication in TB mice with a low compared to a sufficient n-3 PUFA status. Mice were conditioned on an n-3 PUFA-deficient (n-3FAD) or n-3 PUFA-sufficient (n-3FAS) diet for 6 weeks before TB infection. Post-infection at 2 weeks, both groups were switched to an n-3 LCPUFA [eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA)] supplemented diet and euthanized at 4- and 14- days post-treatment. Iron and anemia status, bacterial loads, lung pathology, lung cytokines/chemokines, and lung lipid mediators were measured. Following 14 days of treatment, hemoglobin (Hb) was higher in the n-3FAD than the untreated n-3FAS group (p = 0.022), whereas the n-3FAS (drug) treated control and n-3FAS groups were not. Pro-inflammatory lung cytokines; interleukin-6 (IL-6) (p = 0.011), IL-1α (p = 0.039), MCP1 (p = 0.003), MIP1- α (p = 0.043), and RANTES (p = 0.034); were lower, and the anti-inflammatory cytokine IL-4 (p = 0.002) and growth factor GMCSF (p = 0.007) were higher in the n-3FAD compared with the n-3FAS mice after 14 days. These results suggest that n-3 LCPUFA therapy in TB-infected mice, in combination with TB medication, may improve anemia of infection more in low n-3 fatty acid status than sufficient status mice. Furthermore, the low n-3 fatty acid status TB mice supplemented with n-3 LCPUFA showed comparatively lower cytokine-mediated inflammation despite presenting with lower pro-resolving lipid mediators.

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