lncRNA TUG1 protects intestinal epithelial cells from damage induced by high glucose and high fat via AMPK/SIRT1

Abstract

The incidence of obesity and type 2 diabetes mellitus (T2dM) is increasing year by year and shows a trend towards younger age groups worldwide. it has become a disease that endangers the health of individuals all over the world. among numerous weight loss surgeries, sleeve gastrectomy (SG) has become one of the most common surgical strategies for the treatment of T2dM. However, SG-mediated alterations to the molecular mechanism of metabolism require further investigation. Thus, reverse transcription-quantitative Pcr was used to detect the expression levels of long non-coding (lnc)rna taurine-upregulated gene 1 (TuG1), Sirtuin 1 (SirT1), aMP-activated protein kinase (aMPK) and uncoupling protein 2 (ucP2) in the serum of T2dM patients, as well as in Hiec-6 and SW480 cells following treatment with high glucose and high fat (HGHF). Protein expression was detected by western blotting. cell counting Kit-8 assays were performed to analyze cell viability, and flow cytometry and a Tunel assay was performed to evaluate cell apoptosis. The secretion of ils in the culture medium was detected by conducting eliSas. The results showed that lncrna TuG1 and ucP2 expression was upregulated, SirT1 and aMPK expression levels were decreased by SG. under HGHF conditions, Hiec-6 and SW480 cell viability was inhibited, apoptosis was promoted, TuG1 expression was downregulated, and SirT1 and aMPK expression levels were upregulated. The secretory levels of il-1β, il-6 and il-8 were increased, whereas the secretion of il-10 was decreased under HGHF conditions. lncRNA TUG1 overexpression significantly reversed the effects of HGHF on cell viability, apoptosis and SirT1, aMPK, ucP2 and Bcl-2 expression levels. Together, the findings of the present study demonstrated that lncRNA TuG1 alleviated the damage induced by HGHF in intestinal epithelial cells by downregulating SirT1 and aMPK expression, and upregulating ucP2 expression. Thus, the lncrna TuG1/aMPK/SirT1/ucP2 axis may serve an important role in the treatment of T2dM.

Epigenetic modifications in obesity‐associated diseases

“…Following vertical sleeve gastrectomy, the expression of lncRNA Gm19619 is reduced, leading to improved glucose and lipid metabolism 275 . Sleeve gastrectomy can reverse the upregulation of lncRNA taurine‐upregulated gene 1 (TUG1) induced by high sugar and high fat intake, leading to decreased TUG1 levels which in turn help in regulating blood sugar levels in patients with T2D 276 . Hence, bariatric surgery presents a promising approach for preventing complications in obese patients.…”

Diabetes and diabetic associative diseases: An overview of epigenetic regulations of TUG1

“…TUG1 overexpression countered HGHF effects, suggesting its involvement in mitigating metabolic damage. The TUG1/AMPK/SIRT1/UCP2 axis could have implications for T2DM treatment ( Wei et al, 2022 ). LINC00657, a long non-coding RNA, is gaining prominence for its potential roles in numerous living processes and illnesses.…”

“…Diabetes-induced nephropathy, also known as diabetic kidney disease, develops due to prolonged high blood sugar levels damaging the kidneys' blood vessels and filtering units ( Wei et al, 2022 ). This leads to protein leakage into the urine, impaired filtration, and gradual kidney function decline.…”

H19 and TUG1 lncRNAs as Novel Biomarkers for Irritable Bowel Syndrome in Diabetic Patients

“…It was discovered that the lncRNA TUG1 reduced the apoptosis and inflammatory response generated by the tumor necrosis factor, which has been linked to the etiology of IBS [ 15 ]. Intestinal epithelial cells are protected by lncRNA TUG1 from the damage caused by high glucose and high fat levels [ 16 ].…”