脂肪营养不良与肥胖相关的非酒精性脂肪性肝病中肝脏脂肪堆积、氧化和分泌的不同途径。

Divergent pathways of liver fat accumulation, oxidation, and secretion in lipodystrophy versus obesity-associated NAFLD.

机构信息

Section on Translational Diabetes and Metabolic Syndromes, Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.

Liver & Energy Metabolism Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.

出版信息

Liver Int. 2023 Dec;43(12):2692-2700. doi: 10.1111/liv.15707. Epub 2023 Aug 25.

DOI:10.1111/liv.15707

PMID:37622286

Abstract

BACKGROUND AND AIMS

Fatty liver is common in obesity as well as in partial lipodystrophy (PL) syndromes, characterized by deficient adipose tissue. Insulin resistance is key to fatty liver pathogenesis in both entities. We aimed to compare the contributions of insulin resistance and adipose tissue to hepatic steatosis in PL and non-syndromic, obesity-associated non-alcoholic fatty liver disease (NS-NAFLD).

METHODS

In a cross-sectional comparison of people with NS-NAFLD (N = 73) and PL (N = 27), liver fat was measured by FibroScan controlled attenuation parameter (CAP) and insulin resistance by HOMA-IR, Adipo-IR, and NMR-based LP-IR.

RESULTS

Insulin resistance was greater in PL versus NS-NAFLD by HOMA-IR (p = 0.005), Adipo-IR (p = 0.01) and LP-IR (p = 0.05) while liver fat was comparable (304 vs. 324 dB/m, p = 0.12). Liver fat correlated with HOMA-IR in both groups, but CAP values were lower by 32 dB/m in PL compared with NS-NAFLD for any given HOMA-IR. In contrast, Adipo-IR and LP-IR correlated with CAP only in the NS-NAFLD group, suggesting different pathways for fat accumulation. Plasma free fatty acids, reflecting substrate input from the adipose tissue, were comparable between groups. However, the levels of β-hydroxybutyrate, a marker of β-oxidation, and large triglyceride-rich lipoprotein particles, a marker of VLDL secretion, were both higher in PL (p < 0.001 for both).

CONCLUSION

Liver fat content was comparable in subjects with PL-associated NAFLD and NS-NAFLD, despite worse insulin resistance in partial lipodystrophy. Our data demonstrate higher triglyceride oxidation and export in PL, suggesting a compensatory shift of fat from liver storage into the circulation that does not occur in NS-NAFLD.

摘要

背景和目的

脂肪肝在肥胖症以及部分脂肪营养不良（PL）综合征中很常见，其特征为脂肪组织不足。胰岛素抵抗是这两种疾病发生脂肪肝的关键。我们旨在比较胰岛素抵抗和脂肪组织对 PL 和非综合征性、肥胖相关的非酒精性脂肪性肝病（NS-NAFLD）患者肝脂肪变性的贡献。

方法

在 NS-NAFLD（N=73）和 PL（N=27）患者的横断面比较中，通过 FibroScan 受控衰减参数（CAP）测量肝脂肪，通过 HOMA-IR、Adipo-IR 和基于 NMR 的 LP-IR 测量胰岛素抵抗。

结果

PL 患者的胰岛素抵抗（通过 HOMA-IR、Adipo-IR 和 LP-IR）明显大于 NS-NAFLD 患者（p=0.005、p=0.01 和 p=0.05），而肝脂肪相似（304 与 324 dB/m，p=0.12）。两组患者的肝脂肪均与 HOMA-IR 相关，但 PL 患者的 CAP 值比 NS-NAFLD 患者低 32 dB/m，且具有相同的 HOMA-IR。相比之下，Adipo-IR 和 LP-IR 仅与 NS-NAFLD 组的 CAP 相关，表明脂肪堆积的途径不同。反映脂肪组织底物输入的血浆游离脂肪酸在两组间相似。然而，β-羟丁酸（β-氧化的标志物）和大的富含甘油三酯的脂蛋白颗粒（VLDL 分泌的标志物）的水平在 PL 中均更高（均 p<0.001）。