Adipose tissue dysfunction and visceral fat are associated with hepatic insulin resistance and severity of NASH even in lean individuals

胰岛素抵抗 内科学 内分泌学 脂肪组织 脂解 脂肪因子 甘油三酯 脂联素 脂肪肝 医学 胰岛素 胆固醇 疾病
作者
Chiara Saponaro,Silvia Sabatini,Melania Gaggini,Fabrizia Carli,Chiara Rosso,Vincenzo Positano,Angelo Armandi,Gian Paolo Caviglia,Riccardo Faletti,Elisabetta Bugianesi,Amalia Gastaldelli
出处
期刊:Liver International [Wiley]
卷期号:42 (11): 2418-2427 被引量:48
标识
DOI:10.1111/liv.15377
摘要

Abstract Background & Aims Non‐alcoholic fatty liver disease (NAFLD) is a heterogeneous disorder, but the factors that determine this heterogeneity remain poorly understood. Adipose tissue dysfunction is causally linked to NAFLD since it causes intrahepatic triglyceride (IHTG) accumulation through increased hepatic lipid flow, due to insulin resistance and pro‐inflammatory adipokines release. While many studies in NAFLD have looked at total adiposity (i.e. mainly subcutaneous fat, SC‐AT), it is still unclear the possible impact of visceral fat (VF). Thus, we investigated how VF versus SC‐AT was related to NAFLD severity in lean, overweight and obese individuals versus lean controls. Methods Thirty‐two non‐diabetic NAFLD with liver biopsy (BMI 21.4–34.7 kg/m 2 ) and eight lean individuals (BMI 19.6–22.8 kg/m 2 ) were characterized for fat distribution (VF, SC‐AT and IHTG by magnetic resonance imaging), lipolysis and insulin resistance by tracer infusion, free fatty acids (FFAs) and triglyceride (TAG) concentration and composition (by mass spectrometry). Results Intrahepatic triglyceride was positively associated with lipolysis, adipose tissue insulin resistance (Adipo‐IR), TAG concentrations, and increased saturated/unsaturated FFA ratio. Compared to controls VF was higher in NAFLD (including lean individuals), increased with fibrosis stage and associated with insulin resistance 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 progression independently of BMI, which may allow for evidence‐based prevention and intervention strategies.
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