Lipid metabolism affected by high resistant starch

Already in the correlation studies some metabolites of the lipid metabolism appeared to be altered by RS. For that reason, the lipid metabolism was considered in detail. In several studies, the lipid metabolism or lipid profiles of plasma and/or blood samples were detected to be impacted by dietary fiber, including mainly lipoproteins (e.g. VLDL, HDL, LDL, cholesterol and serum TG) and other lipid markers (Kabir et al. 1998, Hashizume et al. 2012) (Behall et al. 1989, Zhou et al. 2015). Additionally, several studies investigating the impact of dietary fiber on mammals is nicely reviewed by Lattimer and Haub in 2010 (Lattimer and Haub 2010). Furthermore, one study was conducted to investigate the impact of dietary fiber (resistant maltodextrin, RM) on fecal metabolic signatures of donor and recipient fecal microbiota transplanted mice, which appeared to be associated with RM-mediated improvement in mouse metabolic disease models (He et al. 2015). Here, they detected fecal metabolites of cholesterol metabolism, such as mevalonate and coprostanol significantly decreased levels in donor and recipient mice, which indicated an essential role of RM in cholesterol control (He et al. 2015).

However, the impact of dietary fiber on the lipid metabolism of fecal samples, including metabolites involved in several pathways of the human lipid metabolism is rather unknown. Thus, the effect of RS on lipid metabolism should be carefully examined in human studies (Higgins et al. 2004).

Here, the lipid metabolism will be reviewed in detail, focusing on specific pathways of the lipid metabolism, including alpha-linolenic acid metabolism, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, fatty acid biosynthesis, steroid hormone biosynthesis, steroid biosynthesis, arachidonic acid metabolism, glycerolipids metabolism, primary bile acid biosynthesis, secondary bile acid biosynthesis and sphingolipid metabolism.

By running the MassTRIX webserver, the mass signals were not only assigned to compounds, but also to KEGG CIDs and specific pathway information. Therefore, the mass signals assigned to KEGG CIDs, including pathways information of the lipid metabolism, were selected for this analysis. This resulted in 66 metabolites of the lipid metabolism altered through diet. These changes were visualized in a heatmap, as shown in Figure 2.4-13.

Figure 2.4-13: Metabolites of the lipid metabolism impacted through diet.

Heatmap of 66 significant metabolites, displayed in m/z of the lipid metabolism impacted through the baseline, HRS or LRS diet. Pathways of the lipid metabolism, such as alpha-linolenic acid metabolism, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, fatty acid biosynthesis, steroid hormone biosynthesis, steroid biosynthesis, arachidonic acid metabolism, glycerolipids metabolism, primary bile acid biosynthesis, secondary bile acid biosynthesis and sphingolipid metabolism. Further details are listed in Table 6.1-11. From Maier, T. V.; Lucio, M.;

Lee, L. H.; VerBerkmoes, N. C.; Brislawn, C. J.; Bernhardt, J.; Lamendella, R.; McDermott, J. E.; Bergeron, N.;

Heinzmann, S. S.; Morton, J. T.; González, A.; Ackermann, G.; Knight, R.; Riedel, K.; Krauss, R. M.; Schmitt-Kopplin, P.; Jansson, J. K.: Impact of Dietary Resistant Starch on the Human Gut Microbiome, Metaproteome, and Metabolome. mBio vol. 8 no. 5 e01343-17 (2017). Reprinted and modified from (Maier et al. 2017). Copyright (2017) Maier et al.

The mass signals significantly changed were proven by the post hoc Kruskal-Nemenyi test, which is listed in the appendix in Table 6.1-11. Predominately three pathways seem to be highly impacted, which were the steroid hormone biosynthesis, arachidonic acid metabolism and primary bile acid biosynthesis (Maier et al. 2017). Thirteen metabolites of the lipid metabolism were significantly decreased in both

BASELINE HRS LRS

Linoleic acid metabolism; Biosynthesis of unsaturated fatty acids Fatty acid biosynthesis

Fatty acid biosynthesis ; Biosynthesis of unsaturated fatty acids Steroid hormone biosynthesis

Fatty acid biosynthesis ; Biosynthesis of unsaturated fatty acids Biosynthesis of unsaturated fatty acids

Biosynthesis of unsaturated fatty acids Biosynthesis of unsaturated fatty acids Steroid biosynthesis ; Primary bile acid biosynthesis Primary bile acid biosynthesis

Primary bile acid biosynthesis; Steroid hormone biosynthesis Primary bile acid biosynthesis

Steroid biosynthesis;Primary bile acid biosynthesis Primary bile acid biosynthesis ; Steroid hormone biosynthesis Steroid biosynthesis

RS diets compared to the baseline diet. This comprises octadecadienoic acid (C18:2), hexadecenoic acid (C16:1), octadecenoic acid (C18:1) (Maier et al. 2017) and ten metabolites classified as sterol lipids and involved in steroid hormone biosynthesis.

Further, three fatty acids, namely decanoic acid (C10:0), dodecanoic acid (C12:0) and tetradecanoic acid (C14:0), all involved in the fatty acid biosynthesis, were solely increased in fecal samples of the LRS diet compared to the baseline and the HRS diet (Maier et al. 2017). Vastly more metabolites of the lipid metabolism, in fact 50, were significantly increased in the HRS diet, compared to the baseline diet and the LRS diet. It was noticeable that the arachidonic acid metabolism, primary bile acid metabolism, secondary bile acid metabolism and steroid biosynthesis primarily were highly impacted through the HRS diet (Maier et al. 2017). Metabolites involved in the arachidonic acid metabolism impacted through RS were several oxylipins, like hydroxyeicosatetraenoic acid, hydroxyoxoeicosatetraenoic acid, hydroxyoctadecenoic acid, dihydroxyeicosatetraenoic acid, dihydroxyhexadecanoic acid, dihydroxyeicosatrienoic acid, dihydroxyoctadecadienoic acid, dihydroxyoctadecadienoic acid, dihydroxyoctadecenoic acid, trihydroxyeicosatrienoic acid, trihydroxyeicosatetraenoic acid, trihydroxyoctadecadienoic acid, trihydroxyoctadecenoic acid.

Additionally, several metabolites of the primary bile acid metabolism were found to be impacted through the HRS diet, such as trihydroxycholestanoic acid, tetrahydroxycholestane, dihydroxycholestenone, dihydroxycholestenoic acid, hydroxyoxocholestenoic acid, cholestanetriol, dihydroxycholesterol, trihydroxycholestanal, and hydroxycholesterol.

The secondary bile acid metabolism was not strongly affected to a lower extend, since only one metabolite involved was detected to be increased in the HRS diet samples, namely tetrahydroxycholanoic acid. Additionally, four metabolites of the steroid biosynthesis and eight ones of the steroid hormone biosynthesis, which were assigned as sterol lipids were found to be increased in the HRS diet. Further, several fatty acids, both saturated and unsaturated ones involved in the biosynthesis of unsaturated fatty acids were strongly increased in the fecal samples of the participants consuming the HRS diet. Those were octadecanoic acid (C18:0), icosanoic acid (C20:0), docosanoic acid (C22:0), tetracosanoic acid (C24:0), icosenoic acid (C20:1), icosapentanoic acid (C20:5), docosenoic acid (C22:1), docosadienoic acid (C22:2) and tetracosenoic acid (C24:1). Dodecenedioic acid, a metabolite of the alpha-linolenic acid metabolism was observed in the HRS diet.

To date, only little metabolomics research focusing on the impact of RS on a pathway-related level was found, especially in humans. To date, only one research group reported the effect of dietary RS intake in growing pigs (Lu et al. 2016). In accordance with our results, they also detected the lipid metabolism to be increased in pigs consuming a HRS diet (Lu et al. 2016). To conclude, metabolites of the lipid metabolism significantly affected by the baseline diet and by intake of RS were detected. This included a great number of metabolites that were highly impacted by the HRS diet. They were involved in e.g.

arachidonic acid metabolism, primary bile acid metabolism and steroid biosynthesis. Within this study novel links between a RS diet and lipid metabolism were observed.