SOCS3
信号转导
蛋白激酶A
磷酸化
激酶
生物
内科学
内分泌学
生物化学
化学
车站3
医学
作者
Laia Vilà,Núria Roglans,Marta Alegret,Rosa María Galán Sánchez,Manuel Vázquez‐Carrera,Juan C. Laguna
出处
期刊:Hepatology
[Wiley]
日期:2008-07-10
卷期号:48 (5): 1506-1516
被引量:81
摘要
There is controversy regarding whether fructose in liquid beverages constitutes another dietary ingredient of high caloric density or introduces qualitative changes in energy metabolism that further facilitate the appearance of metabolic diseases. Central to this issue is the elucidation of the molecular mechanism responsible for the metabolic alterations induced by fructose ingestion. Fructose administration (10% wt/vol) in the drinking water of Sprague-Dawley male rats for 14 days induced hyperleptinemia and hepatic leptin resistance. This was caused by impairment of the leptin-signal transduction mediated by both janus-activated kinase-2 and the mitogen-activated protein kinase pathway. The subsequent increase in activity in the liver of the unphosphorylated and active form of the forkhead box O1 nuclear factor, which transrepresses peroxisome proliferator-activated receptor alpha activity, and a lack of activation of the adenosine monophosphate-activated protein kinase, led to hypertriglyceridemia and hepatic steatosis. These alterations are attributable to two key events: (1) an increase in the amount of suppressor of cytokine signaling-3 protein, which blocks the phosphorylation and activation of janus-activated kinase-2 and Tyr(985) on the long form of the leptin receptor; and (2) a common deficit of phosphorylation in serine/threonine residues of key proteins in leptin-signal transduction pathways. The latter is probably produced by the early activation of protein phosphatase 2A, and further sustained by the accumulation in liver tissue of ceramide, an activator of protein phosphatase 2A, due to incomplete oxidation of fatty acids.Our data indicate that fructose ingestion as a liquid solution induces qualitative changes in liver metabolism that lead to metabolic diseases.
科研通智能强力驱动
Strongly Powered by AbleSci AI