NASH-related increases in plasma bile acid levels depend on insulin resistance
| Autor: | Grzych, Guillaume, Chavez-Talavera, Oscar, Descat, Amandine, Thuillier, Dorothee, Verrijken, An, Kouach, Mostafa, Legry, Vanessa, Verkindt, Helene, Raverdy, Violeta, Legendre, Benjamin, Caiazzo, Robert, Van Gaal, Luc, Goossens, Jean-Francois, Paumelle, Rejane, Francque, Sven, Pattou, Francois, Haas, Joel T., Tailleux, Anne, Staels, Bart |
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| Přispěvatelé: | Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Recherche translationnelle sur le diabète - U 1190 (RTD), University of Antwerp (UA), Antwerp University Hospital [Edegem] (UZA), ANR-16-RHUS-0006,PreciNASH,PreciNASH(2016), ANR-10-LABX-0046,EGID,EGID Diabetes Pole(2010), European Project: 694717,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) ,ImmunoBile(2016), European Project: 32591,HEPADIP, European Project: 305707,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,RESOLVE(2013), Derudas, Marie-Hélène, PreciNASH - - PreciNASH2016 - ANR-16-RHUS-0006 - RHUS - VALID, EGID Diabetes Pole - - EGID2010 - ANR-10-LABX-0046 - LABX - VALID, Bile acid, immune-metabolism, lipid and glucose homeostasis - ImmunoBile - - H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) 2016-09-01 - 2021-08-31 - 694717 - VALID, Hepatic and adipose tissue and functions in the metabolic syndrome - HEPADIP - 32591 - OLD, A systems biology approach to RESOLVE the molecular pathology of two hallmarks of patients with metabolic syndrome and its co-morbidities, hypertriglyceridemia and low HDL-cholesterol - RESOLVE - - EC:FP7:HEALTH2013-01-01 - 2017-12-31 - 305707 - VALID, Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
GHDCA
glycolithocholic acid taurohyodeoxycholic acid OGTT oral glucose tolerance test GUDCA glycoursodeoxycholic acid TCDCA FXR farnesoid-X-receptor UDCA ADA American Diabetes Association IR insulin resistance GCA glycocholic acid THDCA taurohyodeoxycholic acid HCA T2D LCA lithocholic acid HCA hyocholic acid DCA TCDCA taurochenodeoxycholic acid GCDCA glycochenodeoxycholic acid LCA NASH GCDCA GHCA glycohyocholic acid TCA cholic acid [SDV] Life Sciences [q-bio] FPG glycoursodeoxycholic acid FXR deoxycholic acid glycocholic acid non-alcoholic steatohepatitis TDCA taurodeoxycholic acid HbA1c NASH non-alcoholic steatohepatitis T2D type 2 diabetes Translational study oral glucose tolerance test digestive system BA UDCA ursodeoxycholic acid HDCA glycochenodeoxycholic acid TUDCA tauroursodeoxycholic acid NAFLD OGTT taurochenodeoxycholic acid NAFL non-alcoholic fatty liver GCA FPG fasting plasma glycaemia GDCA glycodeoxycholic acid GLCA glycolithocholic acid C4 bile acids glycodeoxycholic acid nutritional and metabolic diseases HOMA2 homeostatic model assessment 2 hyocholic acid digestive system diseases farnesoid-X-receptor DCA deoxycholic acid GUDCA IR TLCA taurolithocholic acid American Diabetes Association CDCA Human medicine ABOS Biological Atlas of Severe Obesity HDCA hyodeoxycholic acid [SDV]Life Sciences [q-bio] HOMA2 taurodeoxycholic acid taurolithocholic acid C4 7alpha-hydroxy-4-cholesten-3-one insulin resistance Biological Atlas of Severe Obesity taurohyocholic acid MAFLD metabolic associated fatty liver disease CA cholic acid CA THCA GHDCA glycohyodeoxycholic acid Diabetes TLCA glycohyocholic acid ursodeoxycholic acid TUDCA TDCA fasting plasma glycaemia lithocholic acid NAFL BA bile acids chenodeoxycholic acid non-alcoholic fatty liver type 2 diabetes ABOS Research Article NAFLD non-alcoholic fatty liver disease TCA taurocholic acid MAFLD taurocholic acid CDCA chenodeoxycholic acid metabolic associated fatty liver disease glycated haemoglobin homeostatic model assessment 2 Obesity lcsh:RC799-869 tauroursodeoxycholic acid 7alpha-hydroxy-4-cholesten-3-one non-alcoholic fatty liver disease THDCA hyodeoxycholic acid ADA GDCA lcsh:Diseases of the digestive system. Gastroenterology HbA1c glycated haemoglobin GHCA glycohyodeoxycholic acid THCA taurohyocholic acid GLCA |
| Zdroj: | JHEP Reports Innovation in Hepatology JHEP Reports Innovation in Hepatology, 2021, 3 (2), pp.100222. ⟨10.1016/j.jhepr.2020.100222⟩ JHEP Reports Innovation in Hepatology, Elsevier, 2021, 3 (2), pp.100222. ⟨10.1016/j.jhepr.2020.100222⟩ JHEP Reports JHEP Reports, Vol 3, Iss 2, Pp 100222-(2021) |
| ISSN: | 2589-5559 |
| DOI: | 10.1016/j.jhepr.2020.100222⟩ |
| Popis: | Background & Aims Plasma bile acids (BAs) have been extensively studied as pathophysiological actors in non-alcoholic steatohepatitis (NASH). However, results from clinical studies are often complicated by the association of NASH with type 2 diabetes (T2D), obesity, and insulin resistance (IR). Here, we sought to dissect the relationship between NASH, T2D, and plasma BA levels in a large patient cohort. Methods Four groups of patients from the Biological Atlas of Severe Obesity (ABOS) cohort (Clinical Trials number NCT01129297) were included based on the presence or absence of histologically evaluated NASH with or without coincident T2D. Patients were matched for BMI, homeostatic model assessment 2 (HOMA2)-assessed IR, glycated haemoglobin, age, and gender. To study the effect of IR and BMI on the association of plasma BA and NASH, patients from the HEPADIP study were included. In both cohorts, fasting plasma BA concentrations were measured. Results Plasma BA concentrations were higher in NASH compared with No-NASH patients both in T2D and NoT2D patients from the ABOS cohort. As we previously reported that plasma BA levels were unaltered in NASH patients of the HEPADIP cohort, we assessed the impact of BMI and IR on the association of NASH and BA on the combined BA datasets. Our results revealed that NASH-associated increases in plasma total cholic acid (CA) concentrations depend on the degree of HOMA2-assessed systemic IR, but not on β-cell function nor on BMI. Conclusions Plasma BA concentrations are elevated only in those NASH patients exhibiting pronounced IR. Lay summary Non-alcoholic steatohepatitis (NASH) is a progressive liver disease that frequently occurs in patients with obesity and type 2 diabetes. Reliable markers for the diagnosis of NASH are needed. Plasma bile acids have been proposed as NASH biomarkers. Herein, we found that plasma bile acids are only elevated in patients with NASH when significant insulin resistance is present, limiting their utility as NASH markers. Graphical abstract Highlights • Bile acids have been studied as pathophysiological actors and biomarkers in NASH. • Plasma BAs have been reported to be higher in NASH vs. No-NASH patients. • Plasma BAs are altered in patients with T2D, IR, and obesity, risk factors for NASH. • Thus, the independent association between plasma BA increases and NASH is unclear. • NASH-associated increases in plasma BA depend on the degree of insulin sensitivity. |
| Databáze: | OpenAIRE |
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