Back to Search
Start Over
Knockdown of long non-coding RNA Gm10804 suppresses disorders of hepatic glucose and lipid metabolism in diabetes with non-alcoholic fatty liver disease.
- Source :
-
Cell biochemistry and function [Cell Biochem Funct] 2020 Oct; Vol. 38 (7), pp. 839-846. Date of Electronic Publication: 2020 Mar 24. - Publication Year :
- 2020
-
Abstract
- Deregulated glucose and lipid metabolism are the primary underlying manifestations associated with diabetes mellitus (DM) and non-alcoholic fatty liver disease (NAFLD). This study aims to investigate the role of Gm10804, a novel long non-coding RNA (lncRNA), in regulating hepatic glucose and lipid metabolism in DM complicated with NAFLD (DM-NAFLD). Mouse primary hepatocytes exposed to high glucose (HG) were used as a cell model. A mouse DM-NAFLD model was established by high-energy feeding combined with intraperitoneal injection of streptozotocin. The results showed that Gm10804 expression was upregulated in HG-treated hepatocytes and livers from DM-NAFLD mice. Results in hepatocytes in vitro demonstrated that Gm10804 overexpression aggravated, whereas Gm10804 silencing abrogated HG-induced increase in intracellular triglyceride (TG) content, lipid accumulation and expression of hepatic lipogenic proteins (sterol regulatory element-binding proteins 1-c [SREBP-1c] and fatty acid synthase [FAS]) and enzymes for gluconeogenesis (phosphoenolpyruvate carboxykinase [PEPCK] and glucose-6-phosphatase [G6Pase]). Further in vivo assays showed that lentivirus-mediated hepatic knockdown of Gm10804 alleviated hepatic steatosis and lipid accumulation, and decreased expression of hepatic PEPCK, G6Pase, SREBP-1c and FAS in DM-NAFLD mice. In summary, Gm10804 knockdown attenuates hepatic lipid accumulation by ameliorating disorders of hepatic glucose and lipid metabolism in DM-NAFLD. SIGNIFICANCE OF THE STUDY: We first discovered that Gm10804 knockdown attenuated hepatic lipid accumulation by ameliorating disorders of hepatic glucose and lipid metabolism in DM-NAFLD. These results help to understand the pathogenesis and development of DM-NAFLD and provide some clues for further understanding the regulation of lncRNAs in glucose and lipid metabolism.<br /> (© 2020 John Wiley & Sons Ltd.)
- Subjects :
- Animals
Diabetes Mellitus, Experimental complications
Diabetes Mellitus, Experimental genetics
Disease Models, Animal
Down-Regulation drug effects
Glucose pharmacology
Hepatocytes cytology
Hepatocytes drug effects
Hepatocytes metabolism
Liver metabolism
Male
Mice
Non-alcoholic Fatty Liver Disease complications
Non-alcoholic Fatty Liver Disease genetics
Phosphoenolpyruvate Carboxykinase (ATP) genetics
Phosphoenolpyruvate Carboxykinase (ATP) metabolism
RNA Interference
RNA, Long Noncoding antagonists & inhibitors
RNA, Long Noncoding genetics
RNA, Small Interfering metabolism
Sterol Regulatory Element Binding Protein 1 genetics
Sterol Regulatory Element Binding Protein 1 metabolism
Triglycerides metabolism
Up-Regulation drug effects
Diabetes Mellitus, Experimental pathology
Glucose metabolism
Lipid Metabolism drug effects
Non-alcoholic Fatty Liver Disease pathology
RNA, Long Noncoding metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1099-0844
- Volume :
- 38
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cell biochemistry and function
- Publication Type :
- Academic Journal
- Accession number :
- 32212193
- Full Text :
- https://doi.org/10.1002/cbf.3495