Dataset Information

Ultraconserved element uc.333 increases insulin sensitivity by binding to miR-223.

ABSTRACT: Insulin resistance (IR) contributes to diabetes and aging. Ultraconserved elements (UCEs) are a class of long noncoding RNAs (lncRNAs) that are 100% conserved in humans, mice, and rats. We identified the lncRNA uc.333 using an lncRNA microarray and then used quantitative real-time polymerase chain reaction to analyze its expression in the livers of nonalcoholic fatty liver disease (NAFLD) patients, db/db mice, high-fat diet-fed mice, IL-6-treated mice, and TNF-?-treated mice. The underlying mechanisms of uc.333 in IR were investigated using fluorescence in situ hybridization, Western blot, and miRNA microarray analyses. The results revealed that uc.333 expression was decreased in liver tissues from NAFLD patients and treated mice. Furthermore, overexpression of uc.333 decreased IR, whereas knocking down uc.333 increased IR. We also confirmed that uc.333 binds to miR-223 and that the levels of miR-223 were increased in the livers of patients and treated mice. These findings showed that uc.333 improves IR by binding to miR-223; thus, uc.333 may be a useful target for the treatment and prevention of IR.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC7202487 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ultraconserved element uc.333 increases insulin sensitivity by binding to miR-223.

Zhang Yang Y Sun Jingyu J Yao He H Lin Yajun Y Wei Jie J Hu Gang G Guo Jun J Li Jian J

Aging 20200417 8

Insulin resistance (IR) contributes to diabetes and aging. Ultraconserved elements (UCEs) are a class of long noncoding RNAs (lncRNAs) that are 100% conserved in humans, mice, and rats. We identified the lncRNA uc.333 using an lncRNA microarray and then used quantitative real-time polymerase chain reaction to analyze its expression in the livers of nonalcoholic fatty liver disease (NAFLD) patients, db/db mice, high-fat diet-fed mice, IL-6-treated mice, and TNF-α-treated mice. The underlying mech ...[more]

PMID: 32303004

Similar Datasets

Project description:OBJECTIVE:Carbohydrate response element binding protein (ChREBP) is a transcription factor that responds to glucose and activates genes involved in the glycolytic and lipogenic pathways. Recent studies have linked adipose ChREBP to insulin sensitivity in mice. However, while ChREBP is most highly expressed in the liver, the effect of hepatic ChREBP on insulin sensitivity remains unknown. To clarify the importance of hepatic ChREBP on glucose homeostasis, we have generated a knockout mouse model that lacks this protein specifically in the liver (Liver-ChREBP KO). METHODS:Using Liver-ChREBP KO mice, we investigated whether hepatic ChREBP deletion influences insulin sensitivity, glucose homeostasis and the development of hepatic steatosis utilizing various dietary stressors. Furthermore, we determined gene expression changes in response to fasted and fed states in liver, white, and brown adipose tissues. RESULTS:Liver-ChREBP KO mice had impaired insulin sensitivity as indicated by reduced glucose infusion to maintain euglycemia during hyperinsulinemic-euglycemic clamps on both chow (25% lower) and high-fat diet (33% lower) (p < 0.05). This corresponded with attenuated suppression of hepatic glucose production. Although Liver-ChREBP KO mice were protected against carbohydrate-induced hepatic steatosis, they displayed worsened glucose tolerance. Liver-ChREBP KO mice did not show the expected gene expression changes in liver in response to fasted and fed states. Interestingly, hepatic ChREBP deletion also resulted in gene expression changes in white and brown adipose tissues, suggesting inter-tissue communication. This included an almost complete abolition of BAT ChREBP? induction in the fed state (0.15-fold) (p = 0.015) along with reduced lipogenic genes. In contrast, WAT showed inappropriate increases in lipogenic genes in the fasted state along with increased PEPCK1 in both fasted (3.4-fold) and fed (5.1-fold) states (p < 0.0001). CONCLUSIONS:Overall, hepatic ChREBP is protective in regards to hepatic insulin sensitivity and whole body glucose homeostasis. Hepatic ChREBP action can influence other peripheral tissues and is likely essential in coordinating the body's response to different feeding states.

Dataset Information

Ultraconserved element uc.333 increases insulin sensitivity by binding to miR-223.

Publications

Ultraconserved element uc.333 increases insulin sensitivity by binding to miR-223.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets