Research Article Details
| Article ID: | A50418 |
| PMID: | 35398611 |
| Source: | Biochem Biophys Res Commun |
| Title: | Abietic acid alleviates endoplasmic reticulum stress and lipid accumulation in human primary hepatocytes through the AMPK/ORP150 signaling. |
| Abstract: | Abietic acid (AA), the main component of pine resin that has been traditionally used as Asian medicine, has been reported to demonstrate anti-inflammatory activities. Despite this, little is known about the effects of AA on hepatic endoplasmic reticulum (ER) stress and lipid metabolism. This study investigated the impacts of AA on ER stress and steatosis in in vitro obesity models. We found that Treatment with AA reduced lipid deposition and lipogenesis-related proteins expression in human primary hepatocytes. Augmented expression of ER stress markers (phospho-eukaryotic initiation factor-2α (eIF2α) and C/EBP homologous protein (CHOP)) in palmitate-treated hepatocytes were reversed by AA treatment. Further, AA treatment increased the expression of phospho-AMPK and oxygen-regulated protein 150 (ORP150) in hepatocytes. siRNA-associated knockdown of AMPK or ORP150 expression reduced the effects of AA on not only hepatic ER stress but also lipogenesis and apoptosis. These results denote that AA attenuates lipid accumulation in hepatocytes in the presence of palmitate through the suppression of ER stress by AMPK/ORP150 signaling. AA could be a potential candidate for treating non-alcoholic fatty liver disease. |
| DOI: | 10.1016/j.bbrc.2022.04.010 |
| 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 |
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | 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 |
| 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 |