Intrahepatic Expression of Fatty Acid Translocase CD36 Is Increased in Obstructive Sleep Apnea.

Carmelo García-Monzón,Ramón Farré,Elvira del Pozo-Maroto,Patricia Marañón,Brittany Beeler,Águeda González-Rodríguez,Stephania C. Isaza,Yaiza García-García,Esther Rey,Pedro Landete,Isaac Almendros

doi:10.3389/fmed.2020.00450

Abstract

Nocturnal intermittent hypoxia (IH) featuring obstructive sleep apnea (OSA) dysregulates hepatic lipid metabolism and might contribute to the development of non-alcoholic fatty liver disease (NAFLD) observed in OSA patients. However, further research is required to better understanding the molecular mechanisms underlying IH-induced hepatic lipid accumulation. Therefore, the aim of the present study was to determine the effects of OSA on hepatic CD36 expression and the impact of IH by using a mouse model of OSA. Histological analysis, lipid content and CD36 expression were assessed in livers from subjects who underwent liver biopsy and polygraphic study during sleep, and in livers from mice submitted to chronic IH mimicking OSA. Among those who presented OSA features, NAFLD were significantly more frequent than in control subjects with normal respiratory function (77.8 vs. 36.4%, respectively), and showed more severe liver disease. Interestingly, CD36 expression was significantly overexpressed within the liver of OSA patients with respect to controls, and a significant positive correlation was observed between hepatic levels of CD36 and the values of two well-known respiratory parameters that characterized OSA: apnea/hypopnea index (AHI) and oxygen desaturation index (ODI). Moreover, hepatic lipid accumulation as well as induction of hepatic lipogenic genes, and CD36 mRNA and protein expression were significantly higher in livers from mice exposed to IH conditions for 8 weeks than in their corresponding littermates. This study provides novel evidence that IH featuring OSA could contribute to NAFLD setup partly by upregulating hepatic CD36 expression.

Highlights

Non-alcoholic fatty liver disease (NAFLD) is characterized by metabolic dysfunction and accumulation of lipid deposits in the livers of patients in whom alcohol abuse is not the causal agent of disease onset [1]
Distinct clinical studies have reported that obstructive sleep apnea (OSA) is significantly associated with NAFLD severity [26] and there is an increasing experimental evidence that chronic intermittent hypoxia (IH), the best characterized OSA manifestation, is a major trigger for oxidative stress and inflammatory liver injury leading to NAFLD progression [17]
Our findings showed that there were no differences regarding body mass index (BMI) between the two study groups, but waist circumference was significantly higher in patients with OSA, suggesting that is abdominal obesity, but not overall obesity, what has a clinical impact on the features of metabolic syndrome, including OSA and NAFLD

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is characterized by metabolic dysfunction and accumulation of lipid deposits in the livers of patients in whom alcohol abuse is not the causal agent of disease onset [1]. It is well-known that the liver maintains bodily lipid homeostasis by regulating hepatic free fatty acid (FFA) uptake, lipid synthesis, lipid oxidation, and lipid export; an imbalance between these metabolic pathways can lead to an excessive lipid accumulation within the liver [4], being an increased de novo lipogenesis and largely an enhanced uptake of FFAs released from insulin resistant-adipocytes the main sources of these lipid accumulates [5]. Different clinical studies have convincingly shown that the amount of both CD36 mRNA and protein was higher in the livers of biopsy-proven NAFLD patients than in subjects with histologically normal liver [12,13,14]

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