Research Article Details

Article ID: A25658
PMID: 21570653
Source: Eur J Intern Med
Title: Alterations in lipid, carbohydrate and iron metabolism in patients with non-alcoholic steatohepatitis (NASH) and metabolic syndrome.
Abstract: BACKGROUND: NASH (non-alcoholic steatohepatitis) is considered the hepatic manifestation of the metabolic syndrome (MS). We aimed to analyze lipid, carbohydrate, and iron metabolism in NASH. PATIENTS, METHODS: 37 patients with MS (17 M/20 F, 51+/-15 years), elevated transaminases; 25 patients had histologically proven NASH (NAS score&#8805;5), 12 patients had toxic background (nonNASH). 37 age, sex, BMI-matched healthy controls. Lipid variables, LDL-subfractions, iron, ferritin, transferrin (T), transferrin saturation (TS), and hepcidin (H) were measured in patients/controls. Oral glucose tolerance tests were performed. RESULTS: NASH patients with steatosis gr. 2 and 3 (>33% hepatic fat) had higher sd-LDL (mg/dl) concentrations than patients with steatosis gr. 1 (<33%) (p=0.002), nonNASH patients (p=0.03) and controls (p=0.001). Sd absolute (mg/dl) correlated directly with the steatosis grade only in patients with NASH and steatosis >33% (p=0.04). NASH-patients showed higher insulin, C-peptide and IRI values than nonNASH patients (p=0.034; 0.032; 0.04). H was increased in patients versus controls (p<0.001). H correlated with ferritin in MS-patients (p=0.01), correlated directly with sd-LDL (mg/dl) (p=0.017) and IRI (p<0.001) and indirectly with HDL (p=0.05) in NASH. No associations between hepatic inflammation/iron content on liver biopsy and variables of lipid metabolism were found but hepcidin correlated with hepatic inflammation in all patients and with NAS scores in NASH. CONCLUSIONS: NASH-patients show insulin resistance and increased sd-LDL subfractions, suggesting an atherogenic profile. The correlation of H with sd-LDL and IRI, without relation to hepatic iron content suggests a putative link between inflammation, carbohydrate and lipid metabolism in NASH.
DOI: 10.1016/j.ejim.2011.01.011

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

Target ID Target Name GENE Action Class UniProtKB ID Entry Name

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

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
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