The Crosstalk between Hypoxia and Innate Immunity in the Development of Obesity-Related Nonalcoholic Fatty Liver Disease.
Nonalcoholic fatty liver disease (NAFLD) has become a major health issue in western countries in parallel with the dramatic increase in the prevalence of obesity and all obesity related conditions, including respiratory diseases as obstructive sleep apnea-hypopnea syndrome (OSAHS). Interestingly, the severity of the liver damage in obesity-related NAFLD has been associated with the concomitant presence of OSAHS. In the presence of obesity, the proinflammatory state in these patients together with intermittent episodes of hypoxia, characteristic of OSAHS pathogenesis, may lead to an enhanced inflammatory response mediated by a positive feedback loop mechanism that implicates HIF-1 and NFκB. Thus, the severity of liver involvement in obese NAFLD patients with a concomitant diagnosis of OSAHS could be explained. In this review, we focus on the molecular mechanisms underlying the hepatic response to chronic intermittent hypoxia and its interaction with innate immunity in obesity-related NAFLD.
Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, 39008 Santander, Spain ; Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), 39008 Santander, Spain.
María Teresa
MT
Arias-Loste
Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, 39008 Santander, Spain ; Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), 39008 Santander, Spain.
Emilio
E
Fábrega
Transplant and Autoimmunity Group, Research Institute Marqués de Valdecilla (IDIVAL), 39008 Santander, Spain ; Immunology Department, Marqués de Valdecilla University Hospital, 39008 Santander, Spain.
Marcos
M
López-Hoyos
Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, 39008 Santander, Spain ; Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), 39008 Santander, Spain.
Javier
J
Crespo
D000818:Animals; D006801:Humans; D000860:Hypoxia / Q000276:immunology* / Q000473:pathology; D051793:Hypoxia-Inducible Factor 1 / Q000276:immunology; D007113:Immunity, Innate; D008099:Liver / Q000276:immunology* / Q000473:pathology; D016328:NF-kappa B / Q000276:immunology; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000276:immunology* / Q000473:pathology; D020181:Sleep Apnea, Obstructive / Q000209:etiology / Q000276:immunology / Q000473:pathology
D051793:Hypoxia-Inducible Factor 1; D016328:NF-kappa B