Butyrate attenuated fat gain through gut microbiota modulation in db/db mice following dapagliflozin treatment

Tae Jung Oh, Woo Jun Sul, Han Na Oh, Yun Kyung Lee, Hye Li Lim, Sung Hee Choi, Kyong Soo Park, Hak Chul Jang

Research output: Contribution to journalArticle

Abstract

We investigated the effect of a combination treatment with dapagliflozin (Dapa), a sodium-glucose cotransporter-2 inhibitor and butyrate on weight change in db/db mice. Six-week-old male db/db mice were assigned to four groups: vehicle with normal chow diet (NCD), Dapa with NCD, vehicle with 5% sodium butyrate-supplemented NCD (NaB), or Dapa with 5% NaB. After six weeks of treatment, faecal microbiota composition was analysed by sequencing 16S ribosomal RNA genes. In the vehicle with NaB and Dapa + NaB groups, body weight increase was attenuated, and amount of food intake decreased compared with the vehicle with the NCD group. The Dapa + NaB group gained the least total and abdominal fat from baseline. Intestinal microbiota of this group was characterized by a decrease of the Firmicutes to Bacteroidetes ratio, a decrease of Adlercreutzia and Alistipes, as well as an increase of Streptococcus. In addition, the proportion of Adlercreutzia and Alistipes showed a positive correlation with total fat gain, whereas Streptococcus showed a negative correlation. Inferred metagenome function revealed that tryptophan metabolism was upregulated by NaB treatment. We demonstrated a synergistic effect of Dapa and NaB treatment on adiposity reduction, and this phenomenon might be related to intestinal microbiota alteration.

Original languageEnglish
Article number20300
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2019

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