Research Article Details
| Article ID: | A13149 |
| PMID: | 30114411 |
| Source: | Life Sci |
| Title: | C-type natriuretic peptide (CNP) in endothelial cells attenuates hepatic fibrosis and inflammation in non-alcoholic steatohepatitis. |
| Abstract: | AIMS: Our previous study revealed that mice transgenic for endothelial-cell-specific overexpression of CNP (E-CNP Tg mice) are protected against the increased fat weight, inflammation, and insulin resistance associated with high-fat diet (HFD)-induced obesity. In addition, E-CNP overexpression prevented abnormal lipid profiles and metabolism and blocked inflammation in the livers of HFD-fed mice. Because obesity, dyslipidemia, and insulin resistance increase the risk of various liver diseases, including non-alcoholic steatohepatitis (NASH), we here studied the role of E-CNP overexpression in the livers of mice in which NASH was induced through feeding of either HFD or a choline-deficient defined l‑amino-acid diet (CDAA). MAIN METHODS: Wild-type (Wt) and E-CNP Tg mice were fed either a standard diet or HFD for 25 weeks or CDAA for 10 weeks. We then assessed hepatic and serum biochemistry; measured blood glucose during glucose tolerance test (GTT) and insulin tolerance test (ITT); evaluated hepatic fibrosis and inflammation; and performed hepatic histology and gene expression analysis. KEY FINDINGS: Serum triglycerides, total cholesterol, non-esterified fatty acids, asparagine transaminase, glucose tolerance, and insulin resistance were ameliorated by CNP overexpression in endothelial cells of HFD-fed E-CNP Tg mice. In addition, hepatic fibrosis and inflammation were decreased in HFD-fed E-CNP Tg mice compared with HFD-fed Wt mice. CDAA-fed E-CNP Tg mice showed improved glycemic control, but liver parameters, fibrosis, and inflammation were remained elevated and equivalent to those in CDAA-fed Wt mice. SIGNIFICANCE: The overexpression of CNP in endothelial cells has anti-fibrotic and anti-inflammatory effects in liver during HFD-induced NASH in mice. |
| DOI: | 10.1016/j.lfs.2018.08.031 |
| 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 |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| 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 |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D075 | Choline | Supplement | DB00122 | PLD2 product of; PLD1 product of | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |