The Impact Of Short Chain Fatty Acids(SCFAs) On Glycomic Control And Epigenetics In Type 2 Diabetes Mellitus(T2DM) Mice And HepG2 Cells

Type 2 diabetes mellitus(T2DM)is a widespread metabolic disorder characterized by insulin resistance precipitating abnormally high blood glucose levels,genetics and lifestyle have a profound impact on it.Periodontal diseases(PDs)is the destruction of the tissues that support the tooth by accumulation and maturation of oral bacteria on teeth,resulting in tissue autoimmune response.T2DMs and PDs are both common,chronic disease.As already mentioned show that a two-way relationship between T2DM and PDs,with more serious of periodontal tissue were infection in T2DM patients and poorer glycemic control with PDs.Short chain fatty acids(SCFAs)are fatty acid,C atoms is less than 6,also known as volatile fatty acids.The main secondary metabolites of periodontal pathogens include acetic acid,propionic acid,butyric acid,isobutyric and isovaleric.In our studies,SCFAs are the secondary metabolites of periodontal pathogen that as external stimuli to treat mouse to explore their impact on T2DM mice and normal mice.We found that SCFAs cause blood glucose of T2DM mice significantly increased,while the lipid metabolism of T2DM mice become more disordered.However,This phenomenon occured only on T2DM mice,not normal mice.On the other hand,both T2DM mice or normal mice were no significant weight change.Enhancer of zeste homolog 2(EZH2)as a catalytic subunit of PRC,can repress its target gene transcriptionally by trimethylation of lysine 27 on histone H3(H3K27).Silent information regulator 1(SIRT1)is the mammalian homologue of a yeast silencing factor regulating lifespan that is involved in many cellular functions encompassing stress resistance,genomic stability,tumorigenesis,energy metabolism.In the studies of SIRT1 and EZH2,we found that SCFAs could cause the expression of EZH2 gene SIRT1 gene expression increased and decreased respectively in liver of T2DM mice and HepG2 cells.As can be seen from there results,SCFAs had affect the blood glucose changes of T2DM mice,but the weight of T2DM mice did not change,we suspect the elevated of blood glucose in T2DM mice because the glucose tolerance improved,rather than the lack of insulin secretion.SCFAs can increased expression of EZH2 and reduce expression of SIRT1 to repress target gene expression and aggravated diabetes in T2DM mice.