High-fat diet reduces the formation of butyrate, but increases succinate, inflammation, liver fat and cholesterol in rats, while dietary fibre counteracts these effects

Abstract

Introduction: Obesity is linked to type 2 diabetes and risk factors associated to the metabolic syndrome. Consumption of dietary fibres has been shown to have positive metabolic health effects, such as by increasing satiety, lowering blood glucose and cholesterol levels. These effects may be associated with short-chain fatty acids (SCFAs), particularly propionic and butyric acids, formed by microbial degradation of dietary fibres in colon, and by their capacity to reduce low-grade inflammation.

Objective: To investigate whether dietary fibres, giving rise to different SCFAs, would affect metabolic risk markers in low-fat and high-fat diets using a model with conventional rats for 2, 4 and 6 weeks.

Material and methods: Conventional rats were administered low-fat or high-fat diets, for 2, 4 or 6 weeks, supplemented with fermentable dietary fibres, giving rise to different SCFA patterns (pectin - acetic acid; guar gum - propionic acid; or a mixture - butyric acid). At the end of each experimental period, liver fat, cholesterol and triglycerides, serum and caecal SCFAs, plasma cholesterol, and inflammatory cytokines were analysed. The caecal microbiota was analysed after 6 weeks.

Results and discussion: Fermentable dietary fibre decreased weight gain, liver fat, cholesterol and triglyceride content, and changed the formation of SCFAs. The high-fat diet primarily reduced formation of SCFAs but, after a longer experimental period, the formation of propionic and acetic acids recovered. The concentration of succinic acid in the rats increased in high-fat diets with time, indicating harmful effect of high-fat consumption. The dietary fibre partly counteracted these harmful effects and reduced inflammation. Furthermore, the number of Bacteroides was higher with guar gum, while noticeably that of Akkermansia was highest with the fibre-free diet.

Figure 1. Study design.

Schematic illustration of the study design.

Figure 2. Serum concentration of butyric acid.

Serum concentration (µmol/L) of butyric acid in rats fed the three dietary fibre diets for 2, 4 and 6 weeks (means±SEM, n = 7, with exception of groups pectin and fibre-free diets for 4 and 6 weeks, respectively, n = 6).

Figure 3. Weight gain, caecal weight and pH.

A: Weight gain (g), B: weight of caecal content (g), C: caecal tissue weight (g) and D: pH in rats fed the four HFD for 2, 4 and 6 weeks (means ± SEM, n = 7). Values with different letters are significantly different, p<0.05.

Figure 4. Organ weight and analytical markers.

A: liver weight (g), B: spleen weight (g) C: liver fat content (g), D: liver cholesterol (g) and E: liver triglyceride (g) in rats fed the four HFD for 2, 4 and 6 weeks (means ± SEM, n = 7). Values with different letters are significantly different, p<0.05.

Figure 5. Serum concentration of SCFAs.

Serum concentration (µmol/L) of A: acetic acid, B: propionic acid and C: butyric acid in rats fed the four HFD for 2, 4 and 6 weeks (means ± SEM, n = 7, with exception of groups pectin and fibre-free diets for 4 and 6 weeks, respectively, n = 6). Values with different letters are significantly different, p<0.05.

Figure 6. Caecal pools of CAs.

Caecal pools (µmol) of A: acetic acid, B: propionic acid, C: butyric acid, D: lactic acid and E: succinic acid in rats fed the four HFD for 2, 4 and 6 weeks (means ± SEM, n = 7, with exception of group guar gum diet for 6 weeks, respectively, n = 6). Values with different letters are significantly different, p<0.05.

Figure 7. Serum concentration of succinic acid.

Concentration of succinic acid (µmol/L) in serum from rats fed the fibre-free LFD for 2 w and HFD for 2, 4 and 6 weeks (means ± SEM, n = 7, 6, 4 and 6 for LFD 2 w, HFD 2 w, 4 w and 6 w, respectively).

Figure 8. Serum concentration of MCP-1.

Concentration (ng/L) of MCP-1 in portal serum in rats fed the four LFD for 2 weeks and HFD for 2, 4 and 6 weeks (means ± SEM, n = 7, with exceptions of groups fed pectin, guar gum and mixture with low-fat content for 2 weeks, fibre-free with high-fat content for 4 weeks and fibre-free and pectin with high-fat content for 6 weeks, n = 6). Values with different letters are significantly different, p<0.05.

Figure 9. Grouping of the caecal microbiota.

Loading Bi plot of the grouping of the caecal microbiota and analytical markers in rats fed fibre-free (dots), pectin (triangles) and guar gum (squares) diets with high-fat content for 6 weeks (n = 7).

Figure 10. Akkermansia and Bacteroides.

Peak area of T-RFLP peaks for Akkermansia and Bacteroides in rats fed the fibre-free, pectin and guar gum diets for 6 weeks (n = 7). Values with different letters are significantly different, p<0.05.