Research Article Details
| Article ID: | A48338 |
| PMID: | 16181372 |
| Source: | Am J Gastroenterol |
| Title: | Hepatic steatosis in Dunnigan-type familial partial lipodystrophy. |
| Abstract: | OBJECTIVES: Characterization of familial clusters of subjects with metabolic derangements predisposing to hepatic steatosis and nonalcoholic steatohepatitis could facilitate genomic studies to identify risk factors for their development. Dunnigan-type familial partial lipodystrophy (FPLD) is an autosomal dominantly inherited disorder caused by mutations in the LMNA gene. Affected subjects have loss of subcutaneous fat from the extremities and symptoms similar to those characterizing the metabolic syndrome, including insulin resistance and dyslipidemia. The goal of this study was to determine the prevalence of steatosis in subjects with FPLD. METHODS: We examined 18 subjects from six families with FPLD for mutations in LMNA and analyzed plasma lipid and serum glucose concentrations. Liver ultrasound and serum aminotransferase activities were used as indicators of steatosis or steatohepatitis. In two subjects, histological examination of hepatic tissue was performed. RESULTS: All subjects had FPLD-causing mutations in LMNA. Plasma lipids were measured in 17 subjects, 16 of whom had hyperlipidemia and 14 presented with either documented insulin resistance or diabetes mellitus. Hepatic steatosis was present in 15 subjects who had ultrasound examinations and 9 of these had elevated serum aminotransferase activities. Liver biopsy confirmed steatosis in 2 subjects. CONCLUSIONS: Hepatic steatosis is part of the clinical phenotype of FPLD. This familial disorder may provide a human metabolic model system to facilitate genomic and environmental studies to determine risk factors for hepatic steatosis and nonalcoholic steatohepatitis. |
| DOI: | 10.1111/j.1572-0241.2005.00234.x |
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| 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 |
| 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 |
| I06 | 811 | Lipodystrophy | A connective tissue disease that is characterized by marked reduction, absence, and/or the redistribution of adipose tissue. https://www.ncbi.nlm.nih.gov/pubmed/25690482, https://www.ncbi.nlm.nih.gov/pubmed/25833179 | disease of anatomical entity/ musculoskeletal system disease/ connective tissue disease | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | 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 |