Research Article Details
| Article ID: | A52498 |
| PMID: | 26337697 |
| Source: | Obes Surg |
| Title: | Changes in Bile Acid Profile After Laparoscopic Sleeve Gastrectomy are Associated with Improvements in Metabolic Profile and Fatty Liver Disease. |
| Abstract: | BACKGROUND: Bile acids (BA) modulate lipid and glucose metabolism in a feedback loop through production of fibroblast growth factor (FGF) 19 in the terminal ileum. Changes in BA after bariatric surgery may lead to improvements in the metabolic syndrome, including fatty liver disease. This study investigated the relationship between BA and metabolic and inflammatory profiles after laparoscopic sleeve gastrectomy (LSG). METHODS: Patients undergoing LSG had fasting blood samples taken pre-operatively and 6 months post-surgery. Liver injury was measured using cytokeratin (CK) 18 fragments. BA were measured using liquid chromatography tandem-mass spectrometry. FGF-19 was measured using enzyme-linked immunosorbent assay. RESULTS: The study included 18 patients (12 females), with mean age 46.3 years (SEM ± 2.9) and BMI 60.1 kg/m(2) (±2.6). After 6 months, patients lost 39.8 kg (±3.1; p < 0.001). Fourteen patients (78 %) had steatosis. FGF-19 increased from median 128.1 (IQR 89.4-210.1) to 177.1 (121.8-288.9, p = 0.045) at 6 months. Although total BA did not change, primary glycine- and taurine-conjugated BA, cholic acid decreased, and secondary BA, glycine-conjugated urodeoxycholic acid increased over the study period. These changes are associated with reduction in insulin resistance, pro-inflammatory cytokines and CK-18 levels. CONCLUSIONS: The profile of individual BA is altered after LSG. These changes occur in the presence of reductions in inflammatory cytokines and markers of liver injury. This study supports evidence from recent animal models that LSG may have an effect on fatty liver through changes in BA metabolism. |
| DOI: | 10.1007/s11695-015-1878-1 |
| 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 |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| S09 | Bariatric surgery | Metabolic surgery | -- | -- | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T20 | Fatty acid synthase | FASN | inhibitor | Enzyme | P49327 | FAS_HUMAN | Details |
| T29 | Fibroblast growth factor 19 | FGF19 | variant | Secreted | O95750 | FGF19_HUMAN | Details |
| T07 | Bile acid receptor | NR1H4 | agonist | Nuclear hormone receptor | Q96RI1 | NR1H4_HUMAN | 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 | |
|---|---|---|---|---|---|---|---|
| D082 | CK-18 | Miscellany | -- | -- | -- | 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 |