Research Article Details
| Article ID: | A07475 |
| PMID: | 32481590 |
| Source: | Cells |
| Title: | Deletion of Perilipin 5 Protects Against Hepatic Injury in Nonalcoholic Fatty Liver Disease via Missing Inflammasome Activation. |
| Abstract: | Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver diseases with an increasing prevalence due to rising rates of obesity, metabolic syndrome and type II diabetes. Untreated NAFLD may progress to steatohepatitis (NASH) and ultimately liver cirrhosis. NAFLD is characterized by lipid accumulation, and when sufficient excess lipids are obtained, irreversible liver injury may follow. Perilipin 5 (PLIN5), a known lipid droplet coating protein and triglyceride metabolism regulator, is highly expressed in oxidatively modified tissues but it is still unclear how it affects NAFLD/NASH progress. We here studied how PLIN5 affects NAFLD development induced by a 30-week high-fat diet (HFD) administration in wild type and PLIN5 knock out (Plin5-/-) mice. The disruption of PLIN5 induced differences in lipid metabolism during HFD feeding and was associated with reduced hepatic fat accumulation. Surprisingly, Plin5-/- mice showed mitigated activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome, leading to minor hepatic damage. We conclude that PLIN5 is a pleiotropic regulator of hepatic homeostasis in NASH development. Targeting the PLIN5 expression appears critical for protecting the liver from inflammatory activation during chronic NAFLD. |
| DOI: | 10.3390/cells9061346 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | 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 | |
|---|---|---|---|---|---|
| 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 |