Bacteriocin PJ4 from probiotic lactobacillus reduced adipokine and inflammasome in high fat diet induced obesity

Abstract

One of the characteristic features of obesity is increased body weight and accumulation of adipose tissue. It is associated with low grade inflammation and gut dysbiosis. Probiotics and its products could be an ideal strategy to prevent or treat diabetes. In the present study, animals were induced obesity by providing them with high fat diet. Three purified bacteriocins i.e., DT24, PJ4 and TSU4, previously isolated and purified from various probiotic strains, were given as treatment strategies, following the induction of obesity. Upon the completion of the study, animals were sacrificed and were checked for their tissue expression of inflammatory mediators and adipokines. Serum hormone and cytokines analysis were performed to check their inflammatory state. Treatment with purified bacteriocin DT24 did not show any therapeutic effect in any of the parameter studied. Bacteriocin TSU4 on the other hand showed better reversal compared to DT24. Bacteriocin PJ4 showed the most promising results by reversing all the altered parameters significantly. It significantly reversed all the biochemical, immunological in terms of serum cytokines as well as altered morphological characteristics. PJ4 can be further explored to determine its mode of action. The anti-microbial proteins or to be more specific, bacteriocins, which shows broad spectrum efficacy, could be a better alternative in modulating gut microflora for the treatment of obesity and diabetes characteristics. The efficacy of bacteriocin PJ4 may also be due to the source of the host of Lactobacillus.

Keywords: Adipose; Bacteriocin; High fat diet; Lactobacillus; Obesity.

Fig. 1

Gut microflora Analysis of Major Phyla and Species expressed as % difference between five study groups. a % Difference in three major phyla; (b) % difference in four major species. Values are expressed as Mean ± SD of four independent values. Graphpad prism V.6 was used to perform statistical analysis. Significant was compared with % difference obtained in Control-HFD group. * p < 0.05, ** p < 0.01, **** p < 0.0001

Fig. 2

Estimation of Microbial metabolites, i.e., short-chain fatty acids (SCFAs) in different animal groups. (a) Acetate, (b) Propionate, (c) Butyrate. Values are expressed as Mean ± SD of four independent values. Graphpad prism V.6 was used to perform statistical analysis. *when compared with control or #when compared with HFD group, in all figure indicates significance level, ** p < 0.01, **** p < 0.0001 **** p < 0.0001; #### p < 0.0001

Fig. 3

Histopathological analysis of Adipose tissue in different animal groups. (a) control, (b) high fat diet group, (c) high fat diet group treated with DT24, (d) high fat diet group treated with PJ4, (e) high fat diet group treated with TSU4

Fig. 4

Estimation of (a) LPS, (b) insulin, (c) glucagon and (d) free fatty acids in different animal groups. Values are expressed as Mean ± SD of four independent values. Graphpad prism V.6 was used to perform statistical analysis. *when compared with control or #when compared with HFD group, in all figure indicates significance level, **** p < 0.0001**** p < 0.0001; ## p < 0.01, #### p < 0.0001

Fig. 5

Serum Cytokines Analysis in different animal groups. Values are expressed as Mean ± SD of four independent values. Graphpad prism V.6 was used to perform statistical analysis. *when compared with control or #when compared with HFD group, in all figure indicates significance level, * p < 0.05, ** p < 0.01, **** p < 0.0001 * p < 0.05, ** p < 0.01, *** p < 0.001 and **** p < 0.0001; ## p < 0.01, ### p < 0.001 and #### p < 0.0001

Fig. 6

Estimation of (a) TLR-2, (b) TLR-4, (c) NLR-1, (d) NF-kB, (e) NLRP3, (f) GLUT-4, (g) GLP-1 and (h) Caspase-1 in different animal groups. Values are expressed as Mean ± SD of four independent values. Graphpad prism V.6 was used to perform statistical analysis. *when compared with control or #—when compared with HFD group, in all figure indicates significance level, ** p < 0.01, **** p < 0.0001 ** p < 0.01, **** p < 0.0001; # p < 0.05, ## p < 0.01, ### p < 0.001 and #### p < 0.0001

Fig. 7

Estimation of (a) Resistin, (b) Adiponectin, (c) Leptin, (d) PPAR-, (e) PPAR- and (f) Zonal Occludin (ZO-1) in different animal groups. Values are expressed as Mean ± SD of four independent values. Graphpad prism V.6 was used to perform statistical analysis. *when compared with control or #when compared with HFD group, in all figure indicates significance level, * p < 0.05, ** p < 0.01, *** p < 0.001 and **** p < 0.0001* p < 0.05, ** p < 0.01, *** p < 0.001 and **** p < 0.0001; # p < 0.05, ## p < 0.01, #### p < 0.0001