RT Journal Article
SR Electronic
T1 Adipose tissue dysfunction and visceral fat are associated to hepatic insulin resistance and severity of NASH even in lean individuals
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.19.476711
DO 10.1101/2022.01.19.476711
A1 Chiara Saponaro
A1 Silvia Sabatini
A1 Melania Gaggini
A1 Fabrizia Carli
A1 Chiara Rosso
A1 Vincenzo Positano
A1 Angelo Armandi
A1 Gian Paolo Caviglia
A1 Riccardo Faletti
A1 Elisabetta Bugianesi
A1 Amalia Gastaldelli
YR 2022
UL http://biorxiv.org/content/early/2022/01/21/2022.01.19.476711.abstract
AB Background & Aims Nonalcoholic fatty liver disease (NAFLD) is a heterogeneous disorder, but the factors that determine this heterogeneity remain poorly understood. Adipose tissue (AT) dysfunction is causally linked to NAFLD since it causes intrahepatic triglyceride (IHTG) accumulation through increased hepatic lipid flow, due to insulin resistance (IR) and pro-inflammatory adipokines release. While many studies in NAFLD have looked at total adiposity (that is mainly subcutaneous fat, SC-AT), it is still unclear the impact of visceral fat (VF). Thus, we investigated how VF vs. SC-AT were related to NAFLD in lean, overweight, and obese individuals compared to lean controls.Methods Thirty-four non-diabetic NAFLD with liver biopsy and eight lean control individuals (CT) were enrolled in this study. We measured fat distribution (VF, SC-AT and IHTG) by magnetic resonance imaging (MRI), adiponectin concentration, free fatty acids (FFAs) and triglyceride (TAG) concentration and composition by mass spectrometry (MS), lipolysis and IR by tracer infusion.Results IHTG was positively associated with lipolysis, adipose tissue IR, TG concentrations, and increased ratio of saturated/unsaturated fatty acids. VF was higher in NAFLD (including lean individuals) compared to controls, was increased with fibrosis stage and was associated with IR in liver, muscle and adipose tissue, increased lipolysis, and decreased adiponectin levels. Collectively, our results suggest that VF accumulation, given its location close to the liver, is one of the major risk factors for NAFLD.Conclusions These findings propose VF as an early indicator of NAFLD independently of BMI, which may allow for evidence-based prevention and intervention strategies.Competing Interest StatementThe authors have declared no competing interest.NAFLDNonalcoholic fatty liver diseaseATAdipose tissueIHTGIntrahepatic triglycerideIRInsulin resistanceSC-ATSubcutaneous fatVFVisceral fatFFAsFree fatty acidsTAGTriglycerideMSMass spectrometryNASHNon-alcoholic steatohepatitisMRIMagnetic resonance imagingHDLHigh density lipoproteinLDLLow density lipoproteinLFTsLiver function testsAPO-BApolipoprotein BAPO-A1Apolipoprotein A1NASNAFLD activity scoreROIRegion of interestLFFLiver fat fractionEGPEndogenous glucose productionHep-IRHepatic insulin-resistanceMuscle-IRMuscle insulin-resistanceAdipo-IR and Lipo-IRAdipose tissue insulin-resistanceALTAlanine aminotransferaseASTAspartate aminotransferaseGGTGamma-glutamyltransferase