Research Article Details
| Article ID: | A22091 |
| PMID: | 24828988 |
| Source: | Eur J Clin Invest |
| Title: | Hepatic steatosis and PNPLA3 I148M variant are associated with serum Fetuin-A independently of insulin resistance. |
| Abstract: | BACKGROUND & AIMS: Fetuin-A is a liver-derived peptide associated with insulin resistance. Aim of this cross-sectional study was to evaluate whether Fetuin-A is increased in patients with nonalcoholic fatty liver disease (NAFLD) vs. healthy subjects without metabolic abnormalities and the association with insulin resistance and liver damage. To investigate the causal relationship between fatty liver and Fetuin-A, we also analysed whether the inherited I148M PNPLA3 variant modulates Fetuin-A. METHODS: In 137 patients with histological NAFLD, complete metabolic characterization, PNPLA3 genotype, and in 260 healthy subjects without metabolic alterations, Fetuin-A was measured by enzyme-linked immunoabsorbent assay. RESULTS: Serum Fetuin-A was higher in NAFLD patients than in controls (P < 0·0001), independently of age, sex, BMI, insulin resistance, dyslipidemia, adiponectin, PNPLA3 I148M and ALT levels (OR 1·006 95% CI 1·003-1·11; P = 0·003). In NAFLD patients, Fetuin-A was associated with steatosis severity (P = 0·03) and metabolic syndrome features, but not with hepatic inflammation. At multivariate analysis, Fetuin-A levels were associated with BMI, triglycerides, hyperglycemia and PNPLA3 I148M (P = 0·034) independently also of age, sex and ALT levels. As PNPLA3 I148M is a strong and inherited determinant of liver fat without affecting insulin resistance and lipid levels, these data suggest that steatosis has a causal role in determining serum Fetuin-A levels. CONCLUSIONS: Liver fat accumulation and the I148M variant of PNPLA3 are associated with serum Fetuin-A levels independently of insulin resistance. Fetuin-A may be implicated in the pathogenesis of metabolic complications associated with NAFLD. |
| DOI: | 10.1111/eci.12280 |
| 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 |
| 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 |
| 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| 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 |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |