【Introduction】
AMPK (AMP-activated protein kinase), which is involved in overall energy metabolism, suppresses lipid synthesis through its downstream gene expression. Lactobacillus and β-glucan have each been shown to activate AMPK *1, *2. There are reports that the synbiotic effect of Bifidobacteria and Lactobacillus with β-glucan in oats improved the intestinal microflora, weight gain, and reduced metabolic complications of obese mice *3.
In this study, we investigated the synbiotics effect of Lactobacillus plantarum S58 (LP.S58) isolated from kimchi and barley β-glucan on obese mice and its mechanism of action.
【Materials and Methods】
LP.S58 and barley β-glucan were given via oral gavage.
・NC: Normal control diet
・HFD: High-fat diet
・LP.S58: High-fat diet + LP.S58 (1×1010 CFU/kg body weight)
・β-G: High-fat diet + barley β-glucan (500 mg/kg body weight)
・LP.S58 + β-G: LP.S58 (1 × 1010 CFU/kg body weight) + barley β-glucan (500 mg/kg body weight)
Bodyweight was recorded weekly, and feces were collected before the end of the rearing period.
The animals were dissected after fasting overnight, and the following items were measured. Various biochemical tests, measurement of liver and adipose tissue weight in the epididymis, measurement of lipid metabolism-related hormones and inflammatory indices in serum, expression of lipid metabolism-related genes and proteins in liver and adipose tissue, and expression of inflammation-related and tight junction-related genes and proteins in colon tissue. In addition, 16S rRNA analysis of intestinal bacteria in the feces was also performed.
【Results】
Bodyweight, lipid concentration, and fat weight
Compared to NC, HFD showed increased body weight, various lipid concentrations in serum and liver tissue, and obesity-related liver and adipose tissue weight worsening. Compared to HFD, LP.S58 and β-G have suppressed these exacerbations (no significant difference in total cholesterol and LDL-cholesterol levels only with β-G), LP.S58 + β-G have synergistically suppressed.
Expression levels of mRNA and protein in liver and adipose tissues
Compared with NC, mRNA expression levels of PPAR-γ, LPL, C /EBPα, SREBP-1c, FAS, and SCD1 were significantly higher, CPT-1 and HSL were significantly lower in HFD.
In LP.S58 + β-G, the mRNA expression levels of PPAR-γ, LPL, C /EBPα, SREBP-1c, FAS, and SCD1 were significantly suppressed, HSL was significantly increased. The expression levels of some genes were also improved in LP.S58 or β-G, but not as much as the synergistic effect of LP.S58 + β-G.
Compared to NC, the expression level of protein pAMPK was significantly suppressed in HFD, synergistically increased in LP.S58 + β-G, no significant difference in LP.S58 and β-G. The expression levels of PPAR-γ and C /EBPα were significantly higher in HFD, LP.S58 + β-G synergistically suppressed. LP.S58 and β-G also suppressed PPAR-γ in the liver and adipose tissue, and LP.S58 suppressed C /EBPα in adipose tissue.
Lipid metabolism-related hormones in serum
Compared with NC, HFD showed significantly lower levels of adiponectin, GLP-1, and PYY. Compared with HFD, LP.S58 + β-G showed significantly higher levels of adiponectin, LP.S58 and LP.S58 + β-G showed significantly higher GLP-1 and PYY.
Indicators of inflammation in serum and colonic tissue
Compared to NC, HFD had higher concentrations of LPS and four inflammatory cytokines (IL-6, IL-1β, TNF-α, and IFN-γ) in serum and higher gene expression levels of those cytokines in colon tissues. Nevertheless, in LP.S58, β-G, and LP.S58 + β-G, those inflammatory cytokines were suppressed.
Expression levels of tight junction-related mRNAs and proteins
The mRNA expression levels of four tight junction-related proteins (ZO-1, occludin, claudin-7, and Muc2) were lower in HFD than in NC. However, LP.S58 restored the expression of occludin and claudin-7, and LP.S58 + β-G synergistically restored all four. Regarding protein expression levels, LP.S58 + β-G synergistically suppressed the induced decrease in expression of ZO-1, occludin, and claudin-7 by HFD.
Effect on intestinal microflora
Principal component analysis (PCA) showed that NC and HFD had very different microbiomes. HFD and β-G were similar, and LP.S58 and LP.S58+β-G were different from the microbiome of HFD. The relative abundance ratio at the genus level, Lactobacillus, Dubosiella, Allobaculum, Akkermansia, Turicibacter, Faecalibaculum were higher, Helicobacter Ruminococcaceae-UCG-014 and Bacteroides were lower in LP.S58 + β-G compared with HFD.
【Discussion and Conclusion】
We demonstrate that the synbiotics effect of LP.S58 and β-G suppressed lipid accumulation in high-fat diet mice. The following is a summary of the mechanism of action.
・Reduction lipid synthesis via modulating signaling by activating AMPK.
・AMPK activation by increased adiponectin associated with increased GLP-1 and PYY.
・Alleviation of high-fat diet-induced inflammation via the barrier function of colonic mucosa improved by enhancing the expression of tight junction-related proteins.
・Reduction metabolic inflammation induced by a high-fat diet via the expression of genes involved in colonic inflammation suppressed by reducing serum LPS and inflammatory cytokines.
・Suppression changing intestinal microbiome caused by a high-fat diet.
In summary, LP.S58 and β-G can be used as functional food ingredients to prevent lipid accumulation associated with obesity.
【Research institution】
Chongqing University (China)
Chengdu University (China)
*1 Appl Microbiol Biotechnol 103, 14, 5843-50, 2019
*2 Food Chem 145, 198-204, 2014
*3 Mol Metab, 22, 96-109, 2019
A synbiotic consisting of Lactobacillus plantarum S58 and hull-less barley β-glucan ameliorates lipid accumulation in mice fed with a high-fat diet by activating AMPK signaling and modulating the gut microbiota
Carbohydr Polym 243, 116398, 2020
