Effect of yeast beta-glucan on bile acid signaling pathway and its potential effect on high-fat diet induced obesity and related metabolic alteration

Abstract

Obesity is a worldwide health problem and increases risk of other diseases, including cardiovascular disease and diabetes. Researchers have been focusing on the role of bile acids (BA) in obesity. Yet, contradicting results were reported on the association between bile acid and obesity. Through conducting meta-analysis and systematic review of available clinical data, it was found that BA metabolism is altered in obese patients. Fibroblast growth factor (FGF19) was significantly reduced while BA excretion and synthesis was suggested to be increased in obesity. Current available obesity interventions, especially bariatric surgery, affect BA metabolism. Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) modulated BA metabolism, i.e., increased BA and FGF19 level. The results revealed the correlation between obesity and bile acid, which led to the other parts of the study, the effect of yeast beta-glucans on obesity and BA metabolism.

Yeast beta-glucans (Y-BG) are polysaccharides from yeast, and can be classified as particulate yeast beta-glucans (P Y-BG) and soluble yeast beta-glucans (S Y-BG). Previous studies showed that Y-BG alleviate metabolic alterations, including the reduction of blood glucose, TG in high fat diet (HFD)-fed mice. Based on the evidence of the association between bile acid and obesity, as well as the beneficial effect of Y-BG on metabolism, the study investigated the effect of P Y-BG and S Y-BG on HFD-induced obesity in mice, as well as their effect on BA metabolism and signalling pathway in healthy and HFD-fed mice.

The study found no significant beneficial effect of Y-BG on metabolic parameters. Low dose of P Y-BG slightly alleviated HFD-induced metabolic alteration while S Y-BG slightly worsened it. High dose of P Y-BG did not exert more pronounced beneficial effect, only slight improvement on insulin sensitivity was found. Despite the ineffectiveness of Y-BG on obesity and metabolic alterations, Y-BG modulated BA metabolism and Farnesoid X Receptor (FXR) signalling pathway in both healthy and HFD-mice. In healthy mice, P Y-BG was found to be FXR inhibiting, as reflected by the reduced SHP and FGF15 expression. As a result, BA reabsorption and synthesis was increased, leading to elevated liver BA level and reduced fecal BA excretion. S Y-BG behaved similarly in healthy mice as P Y-BG, but did not suppress small heterodimer partner (SHP) and fibroblast growth factory (FGF15) expression in ileum. The inhibition of FXR/FGF15 pathway was found in low dose of P Y-BG in HFD-fed mice, and was suggested to contribute to slightly improved metabolic parameters. Unexpectedly, higher dose of P Y-BG did not amplify the inhibition and metabolic improvements in HFD-fed mice. However, as the effect of HFD differed in the two studies, dose comparison may not be accurate. Apart from BA metabolism, Y-BG affected gut microbiota composition and reduced abundance of secondary BA-producing bacteria in healthy mice, possibly due to the increased BA reabsorption in ileum thus reduced BA level in colon. P Y-BG had slightly different effect on the composition in HFD-fed mice, including the increase of Clostridium hylemonae abundance, possibly due to the alteration of gut microbiota by HFD.