Targeting FFARs / GPRs using SCFAs for immune modulation and diet induced diabetic treatment

Abstract

High calorie Diet intake causes alteration in glucose and lipid metabolism along with gut flora. So, the elevated Gram Negative Bacteria are responsible for increase in Plasma lipopolysaccharide levels which causes inflammation leading to Insulin Resistance. During this condition there is an altered sensing of GPR41 and GPR43. These maintains plasma glucose and lipid homeostasis. The objective of our study was to understand How to reduce the Insulin Resistance and inflammation targeting GPRs by orally giving ligands as SCFAs.Insulin Resistance was induced in mice by giving High Fat Diet and High sugar diet for 60 days. They were subsequently treated by orally giving SCFAs like Acetate, Propionate and Butyrate respectively mixed in diet for 60 days. After treatment effect of SCFAs on GPR41 (FFAR3) and GPR43 (FFAR2) sensitivity, inflammation and gene expression of some receptors such as LXR, ChREBP, SREBP, PPARs and FFARs responsible for glucose and lipid metabolism were checked. When diabetic mice were treated with SCFAs the result showed a reduced plasma glucose and lipid levels as well as inflammation in host. So, decreased fat accumulation in adipose tissue, modulate immune system and normal gene expression of GPRs and also the above mentioned receptors help to improve or reduce insulin resistance in mice. According to our results it could be concluded that SCFAs helps in improvement of inflammation and insulin resistance by reducing fat accumulation in host. Mainly Acetate and Butyrate individually helps in reducing inflammation in mice but according to previous data on this study shows that butyrate is most probable SCFA for treatment against inflammation and insulin resistance. So further butyrate can be used for treatment of type 2 diabetes