Research Article Details
| Article ID: | A15378 |
| PMID: | 28938455 |
| Source: | J Clin Endocrinol Metab |
| Title: | Bile Acid Alterations Are Associated With Insulin Resistance, but Not With NASH, in Obese Subjects. |
| Abstract: | Context: Bile acids (BAs) are signaling molecules controlling energy homeostasis that can be both toxic and protective for the liver. BA alterations have been reported in obesity, insulin resistance (IR), and nonalcoholic steatohepatitis (NASH). However, whether BA alterations contribute to NASH independently of the metabolic status is unclear. Objective: To assess BA alterations associated with NASH independently of body mass index and IR. Design and Setting: Patients visiting the obesity clinic of the Antwerp University Hospital (a tertiary referral facility) were recruited from 2006 to 2014. Patients: Obese patients with biopsy-proven NASH (n = 32) and healthy livers (n = 26) were matched on body mass index and homeostasis model assessment of IR. Main Outcome Measures: Transcriptomic analyses were performed on liver biopsies. Plasma concentrations of 21 BA species and 7α-hydroxy-4-cholesten-3-one, a marker of BA synthesis, were determined by liquid chromatography-tandem mass spectrometry. Plasma fibroblast growth factor 19 was measured by enzyme-linked immunosorbent assay. Results: Plasma BA concentrations did not correlate with any hepatic lesions, whereas, as previously reported, primary BA strongly correlated with IR. Transcriptomic analyses showed unaltered hepatic BA metabolism in NASH patients. In line, plasma 7α-hydroxy-4-cholesten-3-one was unchanged in NASH. Moreover, no sign of hepatic BA accumulation or activation of BA receptors-farnesoid X, pregnane X, and vitamin D receptors-was found. Finally, plasma fibroblast growth factor 19, secondary-to-primary BA, and free-to-conjugated BA ratios were similar, suggesting unaltered intestinal BA metabolism and signaling. Conclusions: In obese patients, BA alterations are related to the metabolic phenotype associated with NASH, especially IR, but not liver necroinflammation. |
| DOI: | 10.1210/jc.2017-01397 |
| 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D387 | Vitamin D | Supplement | DB11094 | -- | Vitamin source drug | 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 |