Research Article Details
| Article ID: | A20699 |
| PMID: | 25790917 |
| Source: | Biochim Biophys Acta |
| Title: | Peroxisomes compensate hepatic lipid overflow in mice with fatty liver. |
| Abstract: | UNLABELLED: Major causes of lipid accumulation in liver are increased import or synthesis or decreased catabolism of fatty acids. The latter is caused by dysfunction of cellular organelles controlling energy homeostasis, i.e., mitochondria. Peroxisomes also appear to be an important organelle in lipid metabolism of hepatocytes, but little is known about their role in the development of non-alcoholic fatty liver disease (NAFLD). To investigate the role of peroxisomes alongside mitochondria in excessive hepatic lipid accumulation, we used leptin-resistant db/db mice on C57BLKS background, a mouse model that develops hyperphagia-induced diabetes with obesity and NAFLD. Proteome and gene expression analyses along with lipid analyses in the liver revealed differential expression of genes related to lipid metabolism and β-oxidation, whereas genes for peroxisomal proteins were predominantly regulated. CONCLUSION: Our investigations show that in fatty liver disease in combination with obesity and diabetes, the hepatocyte-protecting organelle peroxisome is altered. Hence, peroxisomes might indicate a stage of pre-NAFLD, play a role in the early development of NAFLD and appear to be a potential target for treatment and prevention of NAFLD. |
| DOI: | 10.1016/j.bbalip.2015.03.003 |
| 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 |
| 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 |