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

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.

Obstructive Sleep Apnoea and Lipid Metabolism: The Summary of Evidence and Future Perspectives in the Pathophysiology of OSA-Associated Dyslipidaemia

“…However, CD36 expression is also upregulated by the peroxisome proliferator-activated receptor-gamma (PPAR-γ), the expression of which was reported to be decreased in OSA [ 106 ]. Nevertheless, intrahepatic CD36 was increased in mice exposed to IH [ 107 ].…”

Increased Oxygen Desaturation Time During Sleep Is a Risk Factor for NASH in Patients With Obstructive Sleep Apnea: A Prospective Cohort Study

“…The major novelty of the present study is that according to logistic regression analysis adjusted by confounders, a Tc90% equal or higher than 10% was the only polygraphic variable independently associated with NASH in patients with OSA (OR, 2.32; 95% CI: 1.12–4.81, p = 0.023). Because increased Tc90% and ODI are the best markers of nocturnal intermittent hypoxia ( 34 ), our findings showed herein suggest that nocturnal intermittent hypoxia could contribute to NASH development and progression in patients with OSA but, although there is increasing scientific evidence indicating that chronic intermittent hypoxia promotes NAFLD and liver fibrosis in rodents ( 35 – 37 ), further experimental studies are needed to fully elucidate this important issue.…”

Hypoxia and Non-alcoholic Fatty Liver Disease

“…Interestingly, silencing of hif-2α reduced lipid accumulation in hypoxic hepatocytes (20,22), pointing out to HIF2α as a key driver in hepatosteatosis setup. Recently, we have observed an upregulated expression of CD36, together with an increased triglyceride content, in livers from mice exposed to IH, pointing out that IH may also modulate FFA uptake (32).…”