Research Article Details
| Article ID: | A06239 |
| PMID: | 32957701 |
| Source: | Biomolecules |
| Title: | Rescue of Hepatic Phospholipid Remodeling Defectin iPLA2β-Null Mice Attenuates Obese but Not Non-Obese Fatty Liver. |
| Abstract: | Polymorphisms of group VIA calcium-independent phospholipase A2 (iPLA2β orPLA2G6) are positively associated with adiposity, blood lipids, and Type-2 diabetes. Theubiquitously expressed iPLA2β catalyzes the hydrolysis of phospholipids (PLs) to generate a fattyacid and a lysoPL. We studied the role of iPLA2β on PL metabolism in non-alcoholic fatty liverdisease (NAFLD). By using global deletion iPLA2β-null mice, we investigated three NAFLD mousemodels; genetic Ob/Ob and long-term high-fat-diet (HFD) feeding (representing obese NAFLD) aswell as feeding with methionine- and choline-deficient (MCD) diet (representing non-obeseNAFLD). A decrease of hepatic PLs containing monounsaturated- and polyunsaturated fatty acidsand a decrease of the ratio between PLs and cholesterol esters were observed in all three NAFLDmodels. iPLA2β deficiency rescued these decreases in obese, but not in non-obese, NAFLD models.iPLA2β deficiency elicited protection against fatty liver and obesity in the order of Ob/Ob › HFD »MCD. Liver inflammation was not protected in HFD NAFLD, and that liver fibrosis was evenexaggerated in non-obese MCD model. Thus, the rescue of hepatic PL remodeling defect observedin iPLA2β-null mice was critical for the protection against NAFLD and obesity. However, iPLA2βdeletion in specific cell types such as macrophages may render liver inflammation and fibrosis,independent of steatosis protection. |
| DOI: | 10.3390/biom10091332 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| 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 |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| 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 | |
|---|---|---|---|---|---|---|---|
| D258 | Omega 3 PUFA | Chemical drug | DB11133 | PPARG ligand; PPARA activator | Hypolipidemic drug | Under clinical trials | 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 |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D055 | Calcium | Chemical drug | DB01373 | CAST; COMP; CP; BMP4; MGP | -- | Under clinical trials | Details |
| D504 | Polyunsaturated Fatty Acids | Supplement | -- | -- | -- | Under clinical trials | Details |
| D125 | Epanova | Chemical drug | DB11133 | PPARG ligand; PPARA activator | Enhance lipid metabolism | Under clinical trials | Details |