Dataset Information


The long non-coding RNA Gm10768 activates hepatic gluconeogenesis by sequestering microRNA-214 in mice.

ABSTRACT: Overactivated hepatic gluconeogenesis contributes to the pathogenesis of metabolic disorders, including type 2 diabetes. Precise control of hepatic gluconeogenesis is thus critical for maintaining whole-body metabolic homeostasis. Long non-coding RNAs (lncRNAs) have been shown to play key roles in diseases by regulating diverse biological processes, but the function of lncRNAs in maintaining normal physiology, particularly glucose homeostasis in the liver, remains largely unexplored. We identified a novel liver-enriched long non-coding RNA, Gm10768, and examined its expression patterns under pathophysiological conditions. We further adopted gain- and loss-of-function strategies to explore the effect of Gm10768 on hepatic glucose metabolism and the possible molecular mechanism involved. Our results showed that the expression of Gm10768 was significantly increased in the liver of fasted mice and was induced by gluconeogenic hormonal stimuli. Functionally, overexpression of Gm10768 activated hepatic gluconeogenesis in a cell-autonomous manner. In contrast, depletion of Gm10768 suppressed hepatic glucose production both in vitro and in vivo Adenovirus-mediated hepatic knockdown of Gm10768 improved glucose tolerance and hyperglycemia of diabetic db/db mice. Mechanistically, Gm10768 sequestrated microRNA-214 (miR-214) to relieve its suppression on activating transcription factor 4 (ATF4), a positive regulator of hepatic gluconeogenesis. Taken together, we identified Gm10768 as a new lncRNA activating hepatic gluconeogenesis through antagonizing miR-214 in mice.

PROVIDER: S-EPMC5857995 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC5559625 | BioStudies
| S-EPMC9121396 | BioStudies
| S-EPMC3609554 | BioStudies
| S-EPMC4290036 | BioStudies
| S-EPMC3331773 | BioStudies
| S-EPMC3795838 | BioStudies
| S-EPMC3137022 | BioStudies
| S-EPMC8262479 | BioStudies
| S-EPMC8344001 | BioStudies
| S-EPMC6786289 | BioStudies