Research Article Details
| Article ID: | A25347 |
| PMID: | 21940337 |
| Source: | Hepatogastroenterology |
| Title: | Impaired activation of phosphatidylinositol 3-kinase by leptin is a novel mechanism of hepatic leptin resistance in NAFLD. |
| Abstract: | BACKGROUND/AIMS: The aim of this study was to detect the levels of leptin in serum and the expression of leptin, obesity receptor (OB-R), phosphatidylinositol 3-Kinase (p85) (PI3-K p85) and phospho-Akt-kinase (Akt) in non-alcoholic fatty liver disease (NAFLD). METHODOLOGY: The expressions of leptin, OB-R and PI3-K/ Akt kinase pathway were examined by immunohistochemistry. The level of leptin in serum was measured by radioimmunoassay. RESULTS: In agreement with significantly elevated serum leptin levels in NAFLD patients (p<0.05), expression of leptin, OB-R and PI3-K (p85) was significant higher in NAFLD patients (p<0.05) compared with the control patients. In contrast, expression of Akt was significantly down-regulated in the NAFLD patients (p<0.05). Moreover, PI3-K (p85) expression was significantly, positively correlated with leptin (r= 0.365, p<0.05) but negatively correlated with Akt (r=-0.854, p<0.01). CONCLUSIONS: Leptin may be involved in NAFLD pathogenesis by activating the PI3-K/Akt kinase pathway via OB-R and the defective leptin activation of PI3-K is a novel mechanism of leptin resistance in NAFLD. |
| DOI: | 10.5754/hge11005 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs |
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| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
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| 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |