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. 2020 Jul 9;12(7):2037.
doi: 10.3390/nu12072037.

Omega-3 Phospholipids from Krill Oil Enhance Intestinal Fatty Acid Oxidation More Effectively than Omega-3 Triacylglycerols in High-Fat Diet-Fed Obese Mice

Petra Kroupova  1 , Evert M van Schothorst  2 , Jaap Keijer  2 , Annelies Bunschoten  2 , Martin Vodicka  3 , Ilaria Irodenko  1 , Marina Oseeva  1 , Petr Zacek  4 , Jan Kopecky  1 , Martin Rossmeisl  1 , Olga Horakova  1
Affiliations

Omega-3 Phospholipids from Krill Oil Enhance Intestinal Fatty Acid Oxidation More Effectively than Omega-3 Triacylglycerols in High-Fat Diet-Fed Obese Mice

Petra Kroupova et al. Nutrients. .

Abstract

Antisteatotic effects of omega-3 fatty acids (Omega-3) in obese rodents seem to vary depending on the lipid form of their administration. Whether these effects could reflect changes in intestinal metabolism is unknown. Here, we compare Omega-3-containing phospholipids (krill oil; ω3PL-H) and triacylglycerols (ω3TG) in terms of their effects on morphology, gene expression and fatty acid (FA) oxidation in the small intestine. Male C57BL/6N mice were fed for 8 weeks with a high-fat diet (HFD) alone or supplemented with 30 mg/g diet of ω3TG or ω3PL-H. Omega-3 index, reflecting the bioavailability of Omega-3, reached 12.5% and 7.5% in the ω3PL-H and ω3TG groups, respectively. Compared to HFD mice, ω3PL-H but not ω3TG animals had lower body weight gain (-40%), mesenteric adipose tissue (-43%), and hepatic lipid content (-64%). The highest number and expression level of regulated intestinal genes was observed in ω3PL-H mice. The expression of FA ω-oxidation genes was enhanced in both Omega-3-supplemented groups, but gene expression within the FA β-oxidation pathway and functional palmitate oxidation in the proximal ileum was significantly increased only in ω3PL-H mice. In conclusion, enhanced intestinal FA oxidation could contribute to the strong antisteatotic effects of Omega-3 when administered as phospholipids to dietary obese mice.

Keywords: Omega-3 index; Omega-3 phospholipids; high-fat diet; krill oil; small intestine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The effect of high-fat diet (HFD) feeding and its supplementation by Omega-3 on body weight (A), body weight gain (B), mesenteric WAT (C), epididymal WAT (D) and subcutaneous WAT (E) in mice. Tissues were weighed after 8 weeks of dietary intervention, while body weight gain was calculated as difference between Week 7 and 0. Data are means ± SEM (n = 8). *, significantly different vs. HFD; #, significantly different vs. ω3TG; †, significantly different vs. ω3PL-L, $, significantly different vs. ω3PL-H. (p < 0.05, one-way ANOVA).
Figure 2
Figure 2
The effect of long-term Omega-3 supplementation on ectopic fat accumulation in dietary obese mice. After 8 weeks of dietary interventions, the level of TAG accumulation was assessed in the liver (A) and skeletal muscle (B). Data are means ± SEM (n = 8). *, significantly different vs. HFD; #, significantly different vs. ω3TG; †, significantly different vs. ω3PL-L, (p < 0.05, one-way ANOVA).
Figure 3
Figure 3
The long-term Omega-3 dietary supplementation affected FA composition of cell membranes. Distribution of FA in the phospholipid fraction of RBCs (A) and score plot as assessed by partial-least-squares discriminant analysis (PLS-DA) based on the FA composition in total phospholipids of RBC (B) from mice after 8 weeks of dietary intervention. Incorporation of Omega-3 in the RBC membranes expressed as the Omega-3 index (C) or relative content of individual Omega-3, ALA, EPA, DPA and DHA (D). Data are mean percentage of total FA in phospholipid fraction (A) or mean percentage ± SEM (C,D) (n = 8). *, significantly different vs. HFD; #, significantly different vs. ω3TG; †, significantly different vs. ω3PL-L (p < 0.05, one-way ANOVA). For detailed FA composition of RBCs phospholipids including Chow-fed mice, see Table S3.
Figure 4
Figure 4
Small intestine as target of Omega-3 dietary intervention in dietary obese mice. (A–D) Representative hematoxylin-eosin sections of proximal ileum from HFD (A), ω3TG (B), ω3PL-L (C) and ω3 PL-H (D) mice; original magnification, 100x; scale bar, 200 µm (E) Length of villi in proximal ileum and (F) length of small intestine of mice fed HFD with and without supplementation for 8 weeks. Data are means ± SEM (n = 8). *, significantly different vs. HFD; #, significantly different vs. ω3TG; †, significantly different vs. ω3PL-L (p < 0.05, one-way ANOVA). (G–I) The 12 most up- and down- regulated genes compared to HFD as assessed by microarray analysis in whole length of small intestine from mice fed ω3TG (G), ω3PL-L (H) or ω3PL-H (I) diet for 8 weeks (p < 0.05). (J) Venn diagram illustrating the overlap in differentially expressed genes compared to HFD mice as determined by microarray-based RNA analysis in the intestinal samples from ω3TG, ω3PL-L and ω3PL-H mice (p < 0.05). (K–M) Enrichment for Gene Ontology Process terms of genes differentially expressed comparing to HFD in (K) ω3TG, (L) ω3PL-L and (M) ω3PL-H small intestine samples identified by DAVID analysis. Gene Ontology (GO) terms were sorted based on p-values (p < 0.005). For detailed effects of HFD compared to chow-fed mice, see Figure S2.
Figure 5
Figure 5
The effect of Omega-3 supplementation on lipid metabolism in the small intestine of dietary obese mice. (A) Heatmap showing the gene expression of (A) FA oxidation genes, (B) ω-oxidation genes (includes also in A - for better resolution in different color scale compared to A) and (C) genes involved in different processes related to lipid metabolism (as indicated on right side) relative to HFD (p < 0.05). T, lipid transport; Glc, glucose/glycerol transport and metabolism; Chol BA; metabolism and transport of cholesterol and bile acids; O, oxidative phosphorylation; L, leptin signaling; K, ketogenesis. (D) The expression of selected genes of mitochondrial and peroxisomal FA oxidation in proximal ileum. Data were expressed as relative to HFD; HFD = 1. (E) Quantification of FA oxidation rate in proximal ileum. Data are means ± SEM (n = 8). *, significantly different vs. HFD; #, significantly different vs. ω3TG (p < 0.05, one-way ANOVA). For detailed effects of HFD compared to Chow-fed mice, see Figure S2.
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