期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 128, 期 9, 页码 3692-3703出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI120846
关键词
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资金
- University of Colorado Department of Pediatrics Child Health Research Career Development Award [K12-HD068372]
- Colorado Nutrition and Obesity Research Center (NORC) [P30DK048520]
- Colorado Clinical and Translational Science Institute (CCTSI) pilot grant
- [NIH-R24DK090964]
Nonalcoholic fatty liver disease (NAFLD) is a global epidemic in obese children and adults, and the onset might have fetal origins. A growing body of evidence supports the role of developmental programming, whereby the maternal environment affects fetal and infant development, altering the risk profile for disease later in life. Human and nonhuman primate studies of maternal obesity demonstrate that risk factors for pediatric obesity and NAFLD begin in utero. The pathologic mechanisms for NAFLD are multifactorial but have centered on altered mitochondrial function/dysfunction that might precede insulin resistance. Compared with the adult liver, the fetal liver has fewer mitochondria, low activity of the fatty acid metabolic enzyme carnitine palmitoyl-CoA transferase-1, and little or no gluconeogenesis. Exposure to excess maternal fuels during fetal life uniquely alters hepatic fatty acid oxidation, tricarboxylic acid cycle activity, de novo lipogenesis, and mitochondrial health. These events promote increased oxidative stress and excess triglyceride storage, and, together with altered immune function and epigenetic changes, they prime the fetal liver for NAFLD and might drive the risk for nonalcoholic steatohepatitis in the next generation.
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