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OSAS-related inflammatory mechanisms of liver injury in nonalcoholic fatty liver disease.

Paschetta E, Belci P, Alisi A, Liccardo D, Cutrera R, Musso G, Nobili V - Mediators Inflamm. (2015)

Bottom Line: Obstructive sleep apnoea syndrome (OSAS) is a common sleep disorder, affecting over 4% of the general population, and is associated with metabolic syndrome and cardiovascular disease, independent of obesity and traditional risk factors.OSAS has been recently connected to nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in the world, which can be found in 30% of the general adult population.In NAFLD patients, liver disease may be caused by hypoxia both indirectly by promoting inflammation and insulin resistance and directly by enhancing proinflammatory cytokine production and metabolic dysregulation in liver cells.

View Article: PubMed Central - PubMed

Affiliation: Gradenigo Hospital, University of Turin, Corso Regina Margherita, 10132 Turin, Italy.

ABSTRACT
Obstructive sleep apnoea syndrome (OSAS) is a common sleep disorder, affecting over 4% of the general population, and is associated with metabolic syndrome and cardiovascular disease, independent of obesity and traditional risk factors. OSAS has been recently connected to nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in the world, which can be found in 30% of the general adult population. Several studies suggest that the chronic intermittent hypoxia (CIH) of OSAS patients may per se trigger liver injury, inflammation, and fibrogenesis, promoting NAFLD development and the progression from steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In NAFLD patients, liver disease may be caused by hypoxia both indirectly by promoting inflammation and insulin resistance and directly by enhancing proinflammatory cytokine production and metabolic dysregulation in liver cells. In this review, we focus on molecular mechanisms linking OSAS to NAFLD, including hypoxia inducible factor (HIF), nuclear factor kappa B (NF-κB), YKL-40, unfolded protein response, and hypoxic adipose tissue inflammation, which all could provide novel potential therapeutic approaches for the management of NAFLD patients with OSAS.

No MeSH data available.


Related in: MedlinePlus

The relationship between nonalcoholic fatty liver disease (NAFLD) and chronic intermittent hypoxia (CIH). TNF: tumor necrosis factor. IL: interleukine. SREBP-1c: sterol-regulatory-element-binding protein-1c. PPAR: peroxisome proliferator-activated receptor. ER: endoplasmic reticulum.
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fig1: The relationship between nonalcoholic fatty liver disease (NAFLD) and chronic intermittent hypoxia (CIH). TNF: tumor necrosis factor. IL: interleukine. SREBP-1c: sterol-regulatory-element-binding protein-1c. PPAR: peroxisome proliferator-activated receptor. ER: endoplasmic reticulum.

Mentions: The duration of nocturnal haemoglobin desaturation independently predicted the number of liver-infiltrating leukocytes and activated Kupffer cells/macrophages, which are believed to play a key role in the pathogenesis of liver injury in NAFLD [29]. Furthermore, CIH directly activates hypoxia-inducible factor- (HIF-) 1a and HIF-2a, two key transcription factors regulating the expression of genes involved in hepatocyte de novo lipogenesis and free fatty acid oxidation and in Kupffer and hepatic stellate cell activation, eventually promoting hepatic steatosis, necroinflammation, and fibrogenesis [30, 31] (Figure 1).


OSAS-related inflammatory mechanisms of liver injury in nonalcoholic fatty liver disease.

Paschetta E, Belci P, Alisi A, Liccardo D, Cutrera R, Musso G, Nobili V - Mediators Inflamm. (2015)

The relationship between nonalcoholic fatty liver disease (NAFLD) and chronic intermittent hypoxia (CIH). TNF: tumor necrosis factor. IL: interleukine. SREBP-1c: sterol-regulatory-element-binding protein-1c. PPAR: peroxisome proliferator-activated receptor. ER: endoplasmic reticulum.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4383458&req=5

fig1: The relationship between nonalcoholic fatty liver disease (NAFLD) and chronic intermittent hypoxia (CIH). TNF: tumor necrosis factor. IL: interleukine. SREBP-1c: sterol-regulatory-element-binding protein-1c. PPAR: peroxisome proliferator-activated receptor. ER: endoplasmic reticulum.
Mentions: The duration of nocturnal haemoglobin desaturation independently predicted the number of liver-infiltrating leukocytes and activated Kupffer cells/macrophages, which are believed to play a key role in the pathogenesis of liver injury in NAFLD [29]. Furthermore, CIH directly activates hypoxia-inducible factor- (HIF-) 1a and HIF-2a, two key transcription factors regulating the expression of genes involved in hepatocyte de novo lipogenesis and free fatty acid oxidation and in Kupffer and hepatic stellate cell activation, eventually promoting hepatic steatosis, necroinflammation, and fibrogenesis [30, 31] (Figure 1).

Bottom Line: Obstructive sleep apnoea syndrome (OSAS) is a common sleep disorder, affecting over 4% of the general population, and is associated with metabolic syndrome and cardiovascular disease, independent of obesity and traditional risk factors.OSAS has been recently connected to nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in the world, which can be found in 30% of the general adult population.In NAFLD patients, liver disease may be caused by hypoxia both indirectly by promoting inflammation and insulin resistance and directly by enhancing proinflammatory cytokine production and metabolic dysregulation in liver cells.

View Article: PubMed Central - PubMed

Affiliation: Gradenigo Hospital, University of Turin, Corso Regina Margherita, 10132 Turin, Italy.

ABSTRACT
Obstructive sleep apnoea syndrome (OSAS) is a common sleep disorder, affecting over 4% of the general population, and is associated with metabolic syndrome and cardiovascular disease, independent of obesity and traditional risk factors. OSAS has been recently connected to nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in the world, which can be found in 30% of the general adult population. Several studies suggest that the chronic intermittent hypoxia (CIH) of OSAS patients may per se trigger liver injury, inflammation, and fibrogenesis, promoting NAFLD development and the progression from steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In NAFLD patients, liver disease may be caused by hypoxia both indirectly by promoting inflammation and insulin resistance and directly by enhancing proinflammatory cytokine production and metabolic dysregulation in liver cells. In this review, we focus on molecular mechanisms linking OSAS to NAFLD, including hypoxia inducible factor (HIF), nuclear factor kappa B (NF-κB), YKL-40, unfolded protein response, and hypoxic adipose tissue inflammation, which all could provide novel potential therapeutic approaches for the management of NAFLD patients with OSAS.

No MeSH data available.


Related in: MedlinePlus