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. 2016 Dec;60(12):2611-2621.
doi: 10.1002/mnfr.201600305. Epub 2016 Aug 30.

Importance of Propionate for the Repression of Hepatic Lipogenesis and Improvement of Insulin Sensitivity in High-Fat Diet-Induced Obesity

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Free PMC article

Importance of Propionate for the Repression of Hepatic Lipogenesis and Improvement of Insulin Sensitivity in High-Fat Diet-Induced Obesity

Karolin Weitkunat et al. Mol Nutr Food Res. .
Free PMC article

Abstract

Scope: The SCFA acetate (Ac) and propionate (Pr) are major fermentation products of dietary fibers and provide additional energy to the host. We investigated short- and long-term effects of dietary Ac and Pr supplementation on diet-induced obesity and hepatic lipid metabolism.

Methods and results: C3H/HeOuJ mice received high-fat (HF) diets supplemented with 5% SCFA in different Ac:Pr ratios, a high acetate (HF-HAc; 2.5:1 Ac:Pr) or high Pr ratio (HF-HPr; 1:2.5 Ac:Pr) for 6 or 22 weeks. Control diets (low-fat (LF), HF) contained no SCFA. SCFA did not affect body composition but reduced hepatic gene and protein expression of lipogenic enzymes leading to a reduced hepatic triglyceride concentration after 22 weeks in HF-HPr mice. Analysis of long-chain fatty acid composition (liver and plasma phospholipids) showed that supplementation of both ratios led to a lower ω6:ω3 ratio. Pr directly led to increased odd-chain fatty acid (C15:0, C17:0) formation as confirmed in vitro using HepG2 cells. Remarkably, plasma C15:0 was correlated with the attenuation of HF diet-induced insulin resistance.

Conclusion: Dependent on the Ac:Pr ratio, especially odd-chain fatty acid formation and insulin sensitivity are differentially affected, indicating the importance of Pr.

Keywords: Acetate; Energy metabolism; High-fat diet; Obesity; Propionate; SCFA.

Figures

Figure 1
Figure 1
Effects of dietary SCFA on body composition change (A, B) and hepatic triglyceride concentration (C, D) after 6 wks (A, C) and 22 wks (B, D) of intervention. C3H mice were fed a LF diet or HF diet supplemented with 5% SCFA, either with a high acetate ratio (Ac:Pr, 2.5:1, HF‐HAc), a high Pr ratio (Ac:Pr, 1:2.5, HF‐HPr), or without SCFA (HF). Data are mean + SEM, n = 7–10. Means with different letters are significantly different (ANOVA with Bonferroni post hoc test was performed between HF groups, p < 0.05).
Figure 2
Figure 2
Hepatic mRNA expression of enzymes involved in lipid metabolism (A), representative bands (B), and corresponding hepatic protein expression (C) after 6 wks of intervention. C3H mice were fed a HF diet supplemented with 5% SCFA, either with a high acetate ratio (Ac:Pr, 2.5:1, HF‐HAc), a high Pr ratio (Ac:Pr, 1:2.5, HF‐HPr), or without SCFA (HF). HF group was set to 1 and protein results are relative to α‐tubulin. Data are mean + SEM, n = 7–8. Means with different letters are significantly different (ANOVA with Bonferroni post hoc test, p < 0.05).
Figure 3
Figure 3
Effects of dietary SCFA on liver (A) and plasma (B) phospholipid LCFA profile. For detailed information on OCFA, ω3, and ω6 FA composition see Table 4. C3H mice were fed a HF diet with 5% SCFA, either with a high acetate ratio (Ac:Pr, 2.5:1, HF‐HAc), a high Pr ratio (Ac:Pr, 1:2.5, HF‐HPr), or without SCFA (HF) for 6 wks. Data are mean + SEM, n = 9–10. Means with different letters are significantly different (ANOVA with Bonferroni post hoc test, p < 0.05).
Figure 4
Figure 4
mRNA expression (A) and phospholipid fatty acid profile (B, C) of HepG2 cells after incubation with 500 μM acetate or propionate. Ac, acetate; Pr, propionate; M, control medium without SCFA. For detailed information on OCFAs, ω3, and ω6 FA composition see Table 4. Data are mean + SEM, n = 3–4. Means with different letters are significantly different (ANOVA with Bonferroni post hoc test, p < 0.05).
Figure 5
Figure 5
Oral glucose tolerance test in 6 h fasted C3H mice after 20 wks of intervention. Mice were fed a LF or HF diet with 5% SCFA, either with a high acetate ratio (Ac:Pr, 2.5:1, HF‐HAc), a high Pr ratio (Ac:Pr, 1:2.5, HF‐HPr), or without SCFA (HF) for 20 wks. Blood glucose and plasma insulin concentrations before (t = 0 min) and after oral glucose application (t = 15, 30, 60, 120, 180 min) (A) and the corresponding total AUC (B). Data are mean + SEM, n = 9–10. Means with different letters are significantly different (ANOVA with Bonferroni post hoc test was performed between HF groups, p < 0.05). (C) Correlation of C15:0 in plasma phospholipids and calculated AUC of insulin secretion during oGTT.

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References

    1. Zhao L., The gut microbiota and obesity: from correlation to causality. Nat. Rev. Microbiol. 2013, 11, 639–647. - PubMed
    1. Hartstra A. V., Bouter K. E., Backhed F., Nieuwdorp M., Insights into the role of the microbiome in obesity and type 2 diabetes Diabetes Care 2015, 38, 159–165. - PubMed
    1. Ley R. E., Backhed F., Turnbaugh P., Lozupone C. A. et al., Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. USA 2005, 102, 11070–11075. - PMC - PubMed
    1. Ridaura V. K., Faith J. J., Rey F. E., Cheng J. et al., Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 2013, 341, 1079–1089. - PMC - PubMed
    1. Turnbaugh P. J., Backhed F., Fulton L., Gordon J. I., Diet‐induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 2008, 3, 213–223. - PMC - PubMed

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