Research Article Details
| Article ID: | A12310 |
| PMID: | 30504232 |
| Source: | J Lipid Res |
| Title: | Hepatic transcriptome analysis from HFD-fed mice defines a long noncoding RNA regulating cellular cholesterol levels. |
| Abstract: | To elucidate the transcriptomic changes of long noncoding RNAs (lncRNAs) in high-fat diet (HFD)-fed mice, we defined their hepatic transcriptome by RNA sequencing. Aberrant expression of 37 representative lncRNAs and 254 protein-coding RNAs was observed in the livers of HFD-fed mice with insulin resistance compared with the livers from control mice. Of these, 24 lncRNAs and 179 protein-coding RNAs were upregulated, whereas 13 lncRNAs and 75 protein-coding RNAs were downregulated. Functional analyses showed that the aberrantly expressed protein-coding RNAs were enriched in various lipid metabolic processes and in the insulin signaling pathway. Genomic juxtaposition and coexpression patterns identified six pairs of aberrantly expressed lncRNAs and protein-coding genes, consisting of five lncRNAs and five protein-coding genes. Four of these protein-coding genes are targeted genes upregulated by PPARα. As expected, the corresponding lncRNAs were significantly elevated in AML12 cells treated with palmitic acid or the PPARα agonist, WY14643. In Hepa1-6 cells, knockdown of NONMMUG027912 increased the cellular cholesterol level, the expression of cholesterol biosynthesis genes and proteins, and the HMG-CoA reductase activity. This genome-wide profiling of lncRNAs in HFD-fed mice reveals one lncRNA, NONMMUG027912, which is potentially regulated by PPARα and is implicated in the process of cholesterol biosynthesis. |
| DOI: | 10.1194/jlr.M086215 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |