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

Author:

Klein Rachael J.1ORCID,Viana Rodriguez Gracia M.2ORCID,Rotman Yaron2ORCID,Brown Rebecca J.1ORCID

Affiliation:

1. 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

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

Abstract

AbstractBackground and AimsFatty 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).MethodsIn 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.ResultsInsulin 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).ConclusionLiver 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.

Funder

National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

Wiley

Subject

Hepatology

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