M-16: Inhibition of Interferon-Gamma or Palmitate-Induced Inflammation in Type 2 Diabetes by Prebiotic Dietary Metabolites

Poster Presenter

Millicent Yeboah-Awudzi

Graduate Assistant and PhD Student
Louisiana State University
United States

Objectives

To compare the inhibitory activity of prebiotic metabolites including sodium butyrate, sodium propionate or protocatechuic acid against IFN-?- or palmitate-induced inflammation in Type 2 Diabetes.

Method

INS-1cells or human PBMCs from diabetic patients (N=10) were cultured with IFN-? or palmitate with or without sodium butyrate, sodium propionate, a mixture of butyrate/propionate, or protocatechuic acid. Anti-inflammatory biomarkers were measured by ELISA, Western blot and/or RT-PCR.

Results

We hypothesized that short chain fatty acid butyrate or propionate at concentrations that can be found in human plasma will improve insulin sensitivity and inhibit IFN-?- or palmitate-induced inflammation in T2D better than prebiotic anthocyanin metabolite protocatechuic acid. IFN-? (100 ng/ml) induced indoleamine 2,3-dioxygenase (IDO) and transglutaminase-2 (TGAse) in INS-1 cells or human PBMCs after 48 h. Palmitate (400 µM) induced lipotoxicity in INS-1 or human PBMCs after 48 h. IFN-? or palmitate reduced insulin secretion. Butyrate at concentrations that can be found in the human plasma (0-5 mM) dose-dependently suppressed IFN-? or palmitate toxicity while enhancing insulin secretion in INS-1 cells better than propionate at concentrations that can be found in the human plasma (0-10 mM). Propionate (0-10 mM) was more efficient than protocatechuic acid at concentrations (1-100 µM) that can be found in human plasma after regular consumption of large amounts of anthocyanin-rich foods. Butyrate better than propionate better than protocatechuic acid dose-dependently inhibited the expression of IDO, TGAse, and NF-?B genes. Butyrate better than propionate better than protocatechuic acid inhibited the secretion of TNF-a, IL-1ß, IL-6, IL-8, IL-12, and MCP-1 in PBMCs.

Conclusion

Short chain fatty acid butyrate or propionate derived from the fermentation of prebiotic dietary fiber inhibited a wide range of pro-inflammatory biomarkers commonly found in type 2 diabetic individuals better than anthocyanin metabolite protocatechuic acid. Butyrate was more efficient than propionate or protocatechuic acid. Regular consumption of prebiotic dietary fiber-rich foods, which can ferment into short chain fatty acids butyrate and propionate in the distal gastrointestinal tract, will be effective in improving insulin sensitivity and reducing inflammation in T2DM patients.