Genetically Engineered Escherichia coli Nissle 1917 Secreting GLP-1 Analog Exhibits Potential Antiobesity Effect in High-Fat Diet-InducedObesity Mice.

Abstract

This study aimed to investigate the potential antiobesity effect of genetically modified Escherichia coli Nissle 1917 (EcN-GM) in mice fed a high-fat diet (HFD). The mice were randomly divided into six groups: a normal diet group (ND), a HFD group, a HFD + EcN group, and three HFD + EcN-GM groups. The effects of EcN-GM on body weight, food intake, fat pad and organ weight, and an oral glucose tolerance test were measured, in addition to hepatic biochemistry and histological analysis. The mRNA expression of neuropeptides related to food intake regulation in thehypothalamus was also detected. The results showed that EcN-GM decreased body weight, body weight gain, food intake, fat pad weight, and hepatic weight of HFD mice. There were beneficial effects of EcN-GM on blood glucose, hepatic biochemistry, and hepatic histological alterations. A dramatic switch of foodintake-regulating gene expression in thehypothalamus was also observed in mice. This work has revealed that a modified live bacterial therapeutic, EcN-GM, has potential beneficial effects on obesity. This effect may be related to the regulating of the neuropeptide expression of energy intake and expenditure in thehypothalamus. This study demonstrates a successful example of engineered EcN-GM as a novel approach for weight management.