NASH-related increases in plasma bile acid levels depend on insulin resistance

Introduction: Plasma bile acids (BA) 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. Materials and Methods: Four groups of patients from the ABOS cohort (Clin Trials NCT01129297) were included based on presence or absence of histologically evaluated NASH with or without coincident T2D. Patients were matched for BMI, HOMA2-assessed IR, HbA 1c , 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 to 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 -cell function nor on BMI.

Mots clés

ABOS Biological Atlas of Severe Obesity ADA American Diabetes Association BA bile acids Bile acids C4 7alpha-hydroxy-4-cholesten-3-one CA cholic acid CDCA chenodeoxycholic acid DCA deoxycholic acid Diabetes FPG fasting plasma glycaemia FXR farnesoid-X-receptor GCA glycocholic acid GCDCA glycochenodeoxycholic acid GDCA glycodeoxycholic acid GHCA glycohyocholic acid GHDCA glycohyodeoxycholic acid GLCA glycolithocholic acid GUDCA glycoursodeoxycholic acid HCA hyocholic acid HDCA hyodeoxycholic acid HOMA2 homeostatic model assessment 2 HbA1c glycated haemoglobin IR insulin resistance Insulin resistance LCA lithocholic acid MAFLD metabolic associated fatty liver disease NAFL non-alcoholic fatty liver NAFLD non-alcoholic fatty liver disease NASH non-alcoholic steatohepatitis OGTT oral glucose tolerance test Obesity T2D type 2 diabetes TCA taurocholic acid TCDCA taurochenodeoxycholic acid TDCA taurodeoxycholic acid THCA taurohyocholic acid THDCA taurohyodeoxycholic acid TLCA taurolithocholic acid TUDCA tauroursodeoxycholic acid Translational study UDCA ursodeoxycholic acid.

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Sciences du Vivant [q-bio]

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https://inserm.hal.science/inserm-03173334

Soumis le : jeudi 18 mars 2021-13:50:27

Dernière modification le : mardi 1 octobre 2024-15:26:06

Archivage à long terme le : lundi 21 juin 2021-08:45:51

Dates et versions

inserm-03173334 , version 1 (18-03-2021)

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Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

HAL Id : inserm-03173334 , version 1
DOI : 10.1016/j.jhepr.2020.100222
PUBMED : 33615207
PUBMEDCENTRAL : PMC7878982

Citer

Guillaume Grzych, Oscar Chávez-Talavera, Amandine Descat, Dorothée Thuillier, An Verrijken, et al.. NASH-related increases in plasma bile acid levels depend on insulin resistance. JHEP Reports Innovation in Hepatology, 2021, 3 (2), pp.100222. ⟨10.1016/j.jhepr.2020.100222⟩. ⟨inserm-03173334⟩

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