Research Article Details
| Article ID: | A15888 |
| PMID: | 28670394 |
| Source: | Am J Transl Res |
| Title: | PFP alleviates nonalcoholic steatohepatitis fatty liver in both Apo E-/- mice and Changliver cell[S]. |
| Abstract: | High-calorie food leads to nonalcoholic fatty liver disease (NAFLD) through the dysregulation of genes involved in lipid metabolism, but the precise mechanism is still unknown. Pomegranate flowers are used to treat diabetes mellitus in traditional Uighur medicine. Here we sought to investigate the effect and mechanism of pomegranate flower polyphenols (PFP) on NAFLD Apo E-/- mice induced by a high-fat diet (HFD) and whether PFP improves NAFLD through decreasing oxidative stress. PFP supplementation in mice significantly reduced the HFD-induced gains in body weight compared with the mice fed only with HFD. It also significantly reduced HFD-induced increases in serum lipids, including cholesterol and triglyceride. Consistent with the reduced liver weight, hepatic lipid accumulation, and the size of lipid droplets in the epididymal fat pads were also reduced by PFP supplementation. To further investigate how PFP may reduce obesity, we analyzed lipid metabolism-related genes in the liver. PFP supplementation altered expression profiles of several lipid metabolism-related genes, including ACC, AMPK, CPT-1α, FAS, LDLR, Leptin, LXR, PON1, PPAR, SirT3, and SREBP, relative to those in HFD control mice. The expression patterns of these genes observed by quantitative reverse transcriptase-polymerase chain reaction and AMPK, SirT3, ACC2, and CPT-1A expression were confirmed by immunohistochemical assays. Collectively, our results indicate that PFP prevents HFD-induced obesity in Apo E-/- mice, and its anti-obesity effects may be related to the regulation of lipogenesis at the level of transcription. |
| DOI: |
| 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 |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| S07 | Anti-lipogenesis | de novo lipogenesis; de novo lipogenesis; DNL; anti-lipogenic mechanisms; adipogenesis; anti-obesity | stearoyl-CoA desaturase 1 (SCD-1); Acetyl-coenzyme carboxylase; acyl-CoA carboxylase inhibitor (ACC inhibitor); stearoyl Coenzyme A desaturase inhibitor (SCD inhibitor); THR-beta selective agonist; DGAT2 inhibitor; FASN inhibitor | Aramchol; Firsocostat (GS-0976); VK-2809; ION 224 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T01 | 5'-AMP-activated protein kinase subunit beta-1 | PRKAB1 | activator | Kinase | Q9Y478 | AAKB1_HUMAN | Details |
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T19 | Acetyl-CoA carboxylase 2 | ACACB | inhibitor | Enzyme | O00763 | ACACB_HUMAN | Details |
| T20 | Fatty acid synthase | FASN | inhibitor | Enzyme | P49327 | FAS_HUMAN | 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 |
| 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 |