Saponaro Chiara, Sabatini Silvia, Gaggini Melania, Carli Fabrizia, Rosso Chiara, Positano Vincenzo, Armandi Angelo, Caviglia Gian Paolo, Faletti Riccardo, Bugianesi Elisabetta, Gastaldelli Amalia
Cardiometabolic Risk Unit, Institute of Clinical Physiology, CNR, Pisa, Italy.
University of Lille, CHU Lille, Inserm U1190, EGID, Lille, France.
Liver Int. 2022 Nov;42(11):2418-2427. doi: 10.1111/liv.15377. Epub 2022 Aug 18.
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.
Thirty-two non-diabetic NAFLD with liver biopsy (BMI 21.4-34.7 kg/m ) and eight lean individuals (BMI 19.6-22.8 kg/m ) 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).
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.
These findings propose VF as an early indicator of NAFLD progression independently of BMI, which may allow for evidence-based prevention and intervention strategies.
非酒精性脂肪性肝病（NAFLD）是一种异质性疾病，但决定这种异质性的因素仍知之甚少。脂肪组织功能障碍与NAFLD存在因果关系，因为它通过增加肝脏脂质流量导致肝内甘油三酯（IHTG）蓄积，这是由于胰岛素抵抗和促炎脂肪因子释放所致。虽然许多关于NAFLD的研究关注的是总体肥胖（即主要是皮下脂肪，SC-AT），但内脏脂肪（VF）的潜在影响仍不清楚。因此，我们研究了在瘦、超重和肥胖个体与瘦对照组中，VF与SC-AT如何与NAFLD严重程度相关。
对32例经肝活检的非糖尿病NAFLD患者（BMI 21.4 - 34.7kg/m²）和8例瘦个体（BMI 19.6 - 22.8kg/m²）进行脂肪分布（通过磁共振成像测量VF、SC-AT和IHTG）、通过示踪剂输注测定脂解和胰岛素抵抗、游离脂肪酸（FFA）和甘油三酯（TAG）浓度及组成（通过质谱分析）的特征分析。
肝内甘油三酯与脂解、脂肪组织胰岛素抵抗（Adipo-IR）、TAG浓度以及饱和/不饱和FFA比值增加呈正相关。与对照组相比，NAFLD患者（包括瘦个体）的VF更高，随纤维化阶段增加而升高，并且与肝脏、肌肉和脂肪组织的胰岛素抵抗、脂解增加和脂联素水平降低相关。总体而言，我们的结果表明，鉴于VF的位置靠近肝脏，其蓄积是NAFLD的主要危险因素之一。
这些发现表明VF是NAFLD进展的早期指标，独立于BMI，这可能有助于制定基于证据的预防和干预策略。
