Obstructive Sleep Apnea-Hypopnea Syndrome and Nonalcoholic Fatty Liver Disease: Emerging Evidence and Mechanisms

Musso, Giovanni; Olivetti, C; Cassader, Maurizio; Gambino, Roberto

doi:10.1055/s-0032-1306426

Cited by 76 publications

(65 citation statements)

References 108 publications

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“…Inappropriate HIF-1a activation following such stimuli as chronic intermittent hypoxia and cholesterol overload has been found to be involved in NASH pathogenesis (22,62), whereas chronic hypoxia has been implicated in renal injury in early diabetic and obesity-related CKD (63,64) (Fig. 2B).…”

Section: Role Of Cellular Energy Oxygen and Nutrient Sensorsmentioning

confidence: 99%

Fatty Liver and Chronic Kidney Disease: Novel Mechanistic Insights and Therapeutic Opportunities

et al. 2016

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Chronic kidney disease (CKD) is a risk factor for end-stage renal disease (ESRD) and cardiovascular disease (CVD). ESRD or CVD develop in a substantial proportion of patients with CKD receiving standard-of-care therapy, and mortality in CKD remains unchanged. These data suggest that key pathogenetic mechanisms underlying CKD progression go unaffected by current treatments. Growing evidence suggests that nonalcoholic fatty liver disease (NAFLD) and CKD share common pathogenetic mechanisms and potential therapeutic targets. Common nutritional conditions predisposing to both NAFLD and CKD include excessive fructose intake and vitamin D deficiency. Modulation of nuclear transcription factors regulating key pathways of lipid metabolism, inflammation, and fibrosis, including peroxisome proliferatoractivated receptors and farnesoid X receptor, is advancing to stage III clinical development. The relevance of epigenetic regulation in the pathogenesis of NAFLD and CKD is also emerging, and modulation of microRNA21 is a promising therapeutic target. Although single antioxidant supplementation has yielded variable results, modulation of key effectors of redox regulation and molecular sensors of intracellular energy, nutrient, or oxygen status show promising preclinical results. Other emerging therapeutic approaches target key mediators of inflammation, such as chemokines; fibrogenesis, such as galectin-3; or gut dysfunction through gut microbiota manipulation and incretin-based therapies. Furthermore, NAFLD per se affects CKD through lipoprotein metabolism and hepatokine secretion, and conversely, targeting the renal tubule by sodium-glucose cotransporter 2 inhibitors can improve both CKD and NAFLD. Implications for the treatment of NAFLD and CKD are discussed in light of this new therapeutic armamentarium. EPIDEMIOLOGICAL EVIDENCE LINKING NAFLD AND CKDChronic kidney disease (CKD) affects up to 8% of the world's adult population, with its prevalence increasing in an aging population beset by lifestyle-associated diseases such as obesity, the metabolic syndrome, diabetes, hypertension, and smoking (1). CKD may progress to end-stage renal disease (ESRD) and is an important cardiovascular disease (CVD) risk factor. Importantly, most patients with CKD die as a result of CVD before renal replacement therapy is initiated (1).There is potential for improving recognition and treatment of CKD. In the Third National Health and Nutrition Survey, awareness among patients with stage 3 CKD was ,8% (1). Furthermore, ESRD or CVD develop in a substantial proportion of patients with CKD receiving standard-of-care therapy, and all-cause mortality remains unchanged in the CKD population (2). These data suggest that key pathogenetic mechanisms underlying

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Section: Role Of Cellular Energy Oxygen and Nutrient Sensorsmentioning

confidence: 99%

Fatty Liver and Chronic Kidney Disease: Novel Mechanistic Insights and Therapeutic Opportunities

et al. 2016

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“…34 Finally, CIH decreases the liver gene expression of peroxisome proliferatoractivated receptor-a and carnitine palmitoyltransferase 1, which are both involved in b -oxydation. 35 Altogether, among which is an elevation of plasma free fatty acids. This leads to lipid accumulation in both muscle and liver, thus, increasing the already existing insulin resistance and possibly worsening liver injury.…”

Section: Fatty Liver Diseases and Association With Metabolic Phenotypmentioning

confidence: 99%

“…42 Collectively, our actual study and previous animal data suggest that associated or preexisting obesity is required for nocturnal hypoxemia to trigger a shift from already existing hepatic steatosis to an infl ammatory and fi brogenic response in the liver . 35 The endothelium is the key regulator of vascular homeostasis. Alteration in endothelial function precedes the development of morphologic atherosclerotic changes and afterward, clinical complications.…”

Section: Fatty Liver Diseases and Association With Metabolic Phenotypmentioning

confidence: 99%

Nonalcoholic Fatty Liver Disease, Nocturnal Hypoxia, and Endothelial Function in Patients With Sleep Apnea

Minville

Hilleret

Tamisier

et al. 2014

Chest

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“…This process may not only contribute to the increased insulin resistance seen in patients with NAFLD but also it may accelerate the process of liver fibrosis leading to the progression to steatohepatitis, cirrhosis and its complications. 15 In regards to clinical practice, this study provides important insights in evaluating both patients with NAFLD and sleep disorders. First, when assessing the overall cardiovascular and metabolic risk profile of a NAFLD patient, signs and symptoms of sleep disorders should be illicited.…”

Section: Discussionmentioning

confidence: 98%

Association of Sleep Disorders with Nonalcoholic Fatty Liver Disease (NAFLD): A Population-based Study

Mir

Stepanova

Afendy

et al. 2013

Journal of Clinical and Experimental Hepatology

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Background: Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease. In smaller studies, sleep apnea has been previously associated with NAFLD. The aim of this study was to assess the prevalence and independent associations of sleep disorders in patients with NAFLD using recent population-based data. Methods: Three cycles of the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2010 were used. The diagnosis of NAFLD was established as elevated liver enzymes in the absence of all other causes of chronic liver disease. Sleep disorders were diagnosed using sleep disorder questionnaires completed by NHANES participants, and included self-reported history of sleep apnea, insomnia, and restless leg syndrome. The prevalence of sleep disorders was compared between those with and without NAFLD. Results: A total of 10,541 adult NHANES participants with complete demographic, clinical, and laboratory data were included. Of those, 15.0% had NAFLD and 7.2% reported having sleep disorders. Of those with sleep disorders, 64.7% reported history of sleep apnea, 16.0% had history of insomnia, and 4.0% had restless leg syndrome. Individuals with NAFLD were more likely to be male (53.8% vs. 45.7%, P < 0.0001), obese (50.1% vs. 33.4%, P < 0.0001) and had higher prevalence of sleep disorders (9.1% vs. 6.9%, P = 0.0118). In multivariate analysis, having any sleep disorder, sleep apnea and insomnia were all independently associated with NAFLD [OR (95% CI) = 1.40 (1.11-1.76), OR = 1.39 (0.98-1.97), and OR = 2.17 (1.19-3.95); respectively)]. Conclusions: This large population-based data suggests that NAFLD is associated with sleep disorders. Although the exact mechanism is unknown, this association is most likely through metabolic conditions associated with NAFLD. ( J CLIN EXP HEPATOL 2013;3:181-185)

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Obstructive Sleep Apnea-Hypopnea Syndrome and Nonalcoholic Fatty Liver Disease: Emerging Evidence and Mechanisms

Cited by 76 publications

References 108 publications

Fatty Liver and Chronic Kidney Disease: Novel Mechanistic Insights and Therapeutic Opportunities

Fatty Liver and Chronic Kidney Disease: Novel Mechanistic Insights and Therapeutic Opportunities

Nonalcoholic Fatty Liver Disease, Nocturnal Hypoxia, and Endothelial Function in Patients With Sleep Apnea

Association of Sleep Disorders with Nonalcoholic Fatty Liver Disease (NAFLD): A Population-based Study

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