TY - JOUR
T1 - Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism
AU - Sato, Fabio Takeo
AU - Yap, Yu Anne
AU - Crisma, Amanda Rabello
AU - Portovedo, Mariana
AU - Murata, Gilson Masahiro
AU - Hirabara, Sandro Massao
AU - Ribeiro, Willian Rodrigues
AU - Marcantonio Ferreira, Caroline
AU - Cruz, Maysa Mariana
AU - Pereira, Joice Naiara Bertaglia
AU - Payolla, Tanyara Baliani
AU - Guima, Suzana Eiko Sato
AU - Thomas, Andrew Maltez
AU - Setubal, João Carlos
AU - Alonso-Vale, Maria Isabel Cardoso
AU - Santos, Marinilce Fagundes
AU - Curi, Rui
AU - Marino, Eliana
AU - Vinolo, Marco A.R.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Obesity is linked with altered microbial short-chain fatty acids (SCFAs), which are a signature of gut dysbiosis and inflammation. In the present study, we investigated whether tributyrin, a prodrug of the SCFA butyrate, could improve metabolic and inflammatory profiles in diet-induced obese mice. Mice fed a high-fat diet for eight weeks were treated with tributyrin or placebo for another six weeks. We show that obese mice treated with tributyrin had lower body weight gain and an improved insulin responsiveness and glucose metabolism, partly via reduced hepatic triglycerides content. Additionally, tributyrin induced an anti-inflammatory state in the adipose tissue by reduction of Il-1β and Tnf-a and increased Il-10, Tregs cells and M2-macrophages. Moreover, improvement in glucose metabolism and reduction of fat inflammatory states associated with tributyrin treatment were dependent on GPR109A activation. Our results indicate that exogenous targeting of SCFA butyrate attenuates metabolic and inflammatory dysfunction, highlighting a potentially novel approach to tackle obesity.
AB - Obesity is linked with altered microbial short-chain fatty acids (SCFAs), which are a signature of gut dysbiosis and inflammation. In the present study, we investigated whether tributyrin, a prodrug of the SCFA butyrate, could improve metabolic and inflammatory profiles in diet-induced obese mice. Mice fed a high-fat diet for eight weeks were treated with tributyrin or placebo for another six weeks. We show that obese mice treated with tributyrin had lower body weight gain and an improved insulin responsiveness and glucose metabolism, partly via reduced hepatic triglycerides content. Additionally, tributyrin induced an anti-inflammatory state in the adipose tissue by reduction of Il-1β and Tnf-a and increased Il-10, Tregs cells and M2-macrophages. Moreover, improvement in glucose metabolism and reduction of fat inflammatory states associated with tributyrin treatment were dependent on GPR109A activation. Our results indicate that exogenous targeting of SCFA butyrate attenuates metabolic and inflammatory dysfunction, highlighting a potentially novel approach to tackle obesity.
KW - butyrate
KW - dysbiosis
KW - insulin resistance
KW - microbiota
UR - http://www.scopus.com/inward/record.url?scp=85090320109&partnerID=8YFLogxK
U2 - 10.3390/cells9092007
DO - 10.3390/cells9092007
M3 - Article
C2 - 32882837
AN - SCOPUS:85090320109
SN - 2073-4409
VL - 9
JO - Cells
JF - Cells
IS - 9
M1 - 2007
ER -
