XXXX leads to @entity1560 in @entity3392 that is reversed by mechanistic target of @entity3446 (mTOR) inhibition.

@entity1 @entity32 @entity1560 @entity948 @entity2425 @entity9942 @entity7093 @entity409 @entity3446 @entity1561 @entity413 @entity3392 @entity2383
@entity1561 ( @entity1561 ), the accumulation of lipid within hepatocytes, is increasing in prevalence. Increasing @entity948 consumption correlates with this increased prevalence, and rodent studies directly support @entity948 leading to @entity1561 . The mechanisms of @entity1561 and in particular @entity948 -induced lipid accumulation remain unclear, although there is evidence for a role for endoplasmic reticulum (ER) stress and oxidative stress. We have evidence that @entity1561 models demonstrate activation of the target of @entity3446 complex 1 ( @entity7093 ) pathway. We set out to assess the contribution of ER stress, oxidative stress, and @entity7093 up-regulation in the development of @entity1560 in @entity948 -treated larval @entity3392 . @entity3392 were treated with @entity948 or @entity413 as a calorie-matched control. We also treated larvae with @entity3446 , @entity2425 (ER stress), or @entity9942 (oxidative stress). Fish were stained with oil red O to assess @entity409 , and we also performed quantitative polymerase chain reaction (qPCR)and western blot analysis. We performed immunostaining on samples from @entity1 with @entity1561 and @entity1561 ( @entity1561 ). Treatment with @entity948 induced @entity409 , @entity2383 , and ER defects. In addition, @entity948 -treated fish showed activation of inflammatory and lipogenic genes. Treatment with @entity2425 or @entity9942 also induced @entity409 . Expression microarray studies of @entity3392 @entity1561 models showed an elevation of genes downstream of @entity7093 signaling. @entity3446 treatment of @entity948 -treated fish prevented development of @entity1560 , as did treatment of @entity2425 - or @entity9942 -treated fish. Examination of liver samples from @entity1 with @entity1560 demonstrated activation of @entity7093 signaling. CONCLUSION: @entity948 treatment of larval @entity3392 induces @entity409 , @entity32 , and oxidative stress. Our results indicate that @entity7093 activation is required for @entity409 across models of @entity1561 , and in @entity1 . (Hepatology 2014;60:1581-1592).
