Research Article Details
| Article ID: | A47292 |
| PMID: | 18722787 |
| Source: | Cytokine |
| Title: | Fat diet and alcohol-induced steatohepatitis after LPS challenge in mice: role of bioactive TNF and Th1 type cytokines. |
| Abstract: | Obesity with insulin resistance and alcohol are the most frequent causes of steatohepatitis. This work investigates the contribution of bioactive TNF and Th1 type cytokines in a mouse model of steatohepatitis induced by FAT alone or FAT+EtOH and endotoxin. The extent of liver injury and cytokine activation induced by endotoxin in chronic FAT-fed mice, FAT+EtOH-fed mice, or mice fed standard chow were analyzed. Endotoxin administration to either FAT-fed or FAT+EtOH-fed mice increased serum ALT and AST compared to standard chow mice. Immunoreactive TNF was strongly activated by LPS in FAT-fed and FAT+EtOH-fed mice which presented the highest levels, but low levels were found in standard chow mice. In contrast, bioactive TNF was only present in serum of FAT-fed and in particular the highest levels were found in FAT+EtOH-fed mice. Moreover, soluble TNFR2 but not TNFR1 was found in lower amounts in serum of FAT+EtOH-fed mice compared to FAT-fed mice. Steatohepatitis was associated with increased IL-6, IFN-gamma, and iNOS mRNA and proteins. Data show that a moderately FAT diet and low-dose EtOH concur to generate steatohepatitis and TNF liver expression after LPS. In this model, changes in the regulation of TNF are associated with increased expression of IL-6, IFN-gamma, and iNOS. |
| DOI: | 10.1016/j.cyto.2008.07.001 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | 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 |