<p>Hypoxia Suppresses High Fat Diet-Induced Steatosis And Development Of Hepatic Adenomas</p>

Abstract

PurposeNonalcoholic fatty liver disease (NAFLD) is considered the most common form of silent liver disease in the United States and obesity is associated with increased risk of NAFLD. Obstructive sleep apnea (OSA) which is common in obese individuals is associated with a greater incidence of NAFLD, which in turn, increases the risk for hepatocellular carcinoma (HCC). It is unclear how obesity, OSA and NAFLD interrelate nor how they collectively contribute to an increased risk for developing HCC.Patients and methodsMale BALB/c mice were exposed to diethylnitrosamine and phenobarbital followed by 48 weeks of either standard chow diet (chow), chow with hypoxia, high-fat diet, or a combination of hypoxia and high-fat diet. We noninvasively monitored tumor development using micro-CT imaging. We tracked the total weight gained throughout the study. We evaluated liver histology, fat accumulation, carbonic anhydrase 9 (CA9) and hypoxia-inducible factor 1-alpha (HIF-1α) expression, as well as, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT).ResultsA high-fat diet without hypoxia led to the development of obesity that induced hepatic steatosis and promoted tumorigenesis. Animals on a high-fat diet and that were also exposed to hypoxia had lower total weight gain, lower steatosis, lower serum AST and ALT levels, and fewer number of hepatic adenomas than a high-fat diet without hypoxia.ConclusionThese findings suggest that hypoxia abrogates obesity, hepatic steatosis, and hepatic tumorigenesis related to a high-fat diet.

The Effects of Naringenin on miRNA-mRNA Profiles in HepaRG Cells

“…These 19 DEGs enriched to metabolism are primarily involved in insulin sensitivity, lipid accumulation, glycogen storage, and energy expenditure. Previous studies reported that the down-regulation of ALOX15 in alcohol-induced mice liver damage [ 18 ], CA9 in BALB/c mice [ 19 ], TH in nonalcoholic fatty liver disease (NAFLD) [ 20 ], HKDC1 [ 21 ], and the up-regulation of UGDH [ 22 ] can significantly relieve oxidative stress, lipid accumulation, and liver damage. Knockdown of NDUFA4L2 suppressed ROS accumulation and apoptosis in hepatocellular carcinoma (HCC) cells [ 23 ].…”

Sleep apnea 20/20: a 20-year cohort that continues to inform the next 20 years

“…6 Such perspective calls for a more in-depth understanding of the molecular and cellular mechanisms that underpin the relationship between OSA and cancer biology before embarking on a large and expensive cohort. 11,12 While limitations of space and competence in the area of cancer biology prevent us from delving deeper, it would suffice to say that the work by Marshall et al has spurred intense investigation into this important area.…”