Bifidobacterium animalis subsp. lactis GCL2505 modulates host energy metabolism via the short-chain fatty acid receptor GPR43.

Ryo Aoki,Kohei Kamikado,Hiroko Horiuchi,Ikuo Kimura,Tomohiko Nishijima,Akiho Nakatani,Natsuki Suganuma

doi:10.1038/s41598-020-60984-6

Ryo Aoki, Kohei Kamikado + Show 5 more

Open Access

https://doi.org/10.1038/s41598-020-60984-6

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Abstract

Short-chain fatty acids (SCFAs), which are metabolites derived from the fermentation of dietary fibre by the gut microbiota, are important for host metabolic health. There is interest in probiotics for their beneficial effects on metabolic disorders, such as obesity, but the underlying mechanisms remain largely unknown. In this study, we evaluated whether Bifidobacterium animalis subsp. lactis GCL2505 (GCL2505), a probiotic strain capable of proliferating and increasing SCFA levels in the gut, exerts anti-metabolic syndrome effects via the SCFA receptor G protein-coupled receptor 43 (GPR43). A GCL2505 treatment suppressed body fat accumulation, improved glucose tolerance, and enhanced systemic fatty acid oxidation in high-fat diet (HFD)-fed wild type (WT) mice, whereas these effects were not observed in HFD-fed Gpr43 knockout (Gpr43−/−) mice. Caecal and plasma acetate levels were elevated by GCL2505 in WT and Gpr43−/− mice, but the negative correlation between plasma acetate levels and body fat accumulation was observed only in WT mice. We further demonstrated that GCL2505 suppressed insulin signalling in the adipose tissue via GPR43. These results suggested that increases in SCFA levels in response to GCL2505 enhance host energy expenditure, which decreases fat accumulation via activated GPR43.

Highlights

Metabolic syndrome, which has emerged as a worldwide epidemic and a major public health issue[1], is primarily characterised by obesity, insulin resistance, hyperlipidaemia, and hypertension
We previously reported that acetate suppresses insulin signalling in adipocytes, thereby inhibiting the accumulation of fat induced by a high-fat diet (HFD) as well as promoting the metabolism of unincorporated lipids and glucose in other tissues[10]
The GCL2505 treatment improved glucose tolerance (Fig. 1b,c). Since both the trend of lowered blood glucose levels and the significant decrease in the area under the curve (AUC) during insulin tolerance test were observed in GCL2505-treated mice compared with saline-treated mice, insulin tolerance was improved by GCL2505 treatment (Fig. 1d,e)

Summary

Introduction

Metabolic syndrome, which has emerged as a worldwide epidemic and a major public health issue[1], is primarily characterised by obesity, insulin resistance, hyperlipidaemia, and hypertension. Changes in gut microbiota, such as decreases in the abundance of beneficial bacteria—for example, short-chain fatty acid (SCFA)-producing bacteria—and increases in the abundance of pro-inflammatory/pathogenic bacteria, are associated with the development of host metabolic abnormalities[4,5] These observations suggest that modulating the gut microbiota is an effective approach for treating obesity and metabolic syndrome. We previously reported that acetate suppresses insulin signalling in adipocytes, thereby inhibiting the accumulation of fat induced by a high-fat diet (HFD) as well as promoting the metabolism of unincorporated lipids and glucose in other tissues[10] These effects are not observed in Gpr[43] knockout (Gpr43−/−) mice, suggesting that SCFA-activated GPR43 is important for the storage of fat in white adipose tissue and the metabolism of lipids and glucose in other tissues. To elucidate the involvement of increased SCFA abundance in the anti-metabolic syndrome effects of GCL2505, we assessed the effects of GCL2505 on metabolic parameters and SCFA levels in Gpr43−/− and wild type (WT) mice

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