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J Clin Biochem Nutr. 2014 Jul;55(1):40-7. doi: 10.3164/jcbn.13-100. Epub 2014 May 13.

Maternal protein restriction induces alterations in hepatic tumor necrosis factor-α/CYP7A1 signaling and disorders regulation of cholesterol metabolism in the adult rat offspring.

Author information

1
Key Laboratory of Health Ministry for Congenital Malformations, Shengjing Hospital of China Medical University, 36th, Sanhao Street, Heping district, Shenyang 110004, China.
2
Virus Laboratory, Shengjing Hospital of China Medical University, 36th, Sanhao Street, Heping district, Shenyang 110004, China.
3
Department of Pathology, Shengjing Hospital of China Medical University, 36th, Sanhao Street, Heping district, Shenyang 110004, China.
4
Department of Pediatrics, Shengjing Hospital of China Medical University, 36th, Sanhao Street, Heping district, Shenyang 110004, China.

Abstract

It is well recognized that adverse events in utero impair fetal development and lead to the development of obesity and metabolic syndrome in adulthood. To investigate the mechanisms linking impaired fetal growth to increased cholesterol, an important clinical risk factor characterizing the metabolic syndrome and cardiovascular disease, we examined the impact of maternal undernutrition on tumor necrosis factor-α (TNF-α)/c-jun N-terminal kinase (JNK) signaling pathway and the cholesterol 7α-hydroxylase (CYP7A1) expression in the livers of the offspring with a protein restriction model. The male offspring with intrauterine growth restriction (IUGR) caused by the isocaloric low-protein diet showed decreased liver weight at birth and augmented circulation and hepatic cholesterol levels at 40 weeks of age. Maternal undernutrition significantly upregulated cytokine TNF-α expression and JNK phospholytion levels in the livers from fetal age to adulthood. Elevated JNK phospholytion could be linked to downregulated hepatocyte nuclear factor-4α and CYP7A1 expression, subsequently led to higher hepatic cholesterol. This work demonstrated that intrauterine malnutrition-induced IUGR might result in intrinsic disorder in hepatic TNF-α/CYP7A1 signaling, and contribute to the development of hypercholesterolemia in later life.

KEYWORDS:

CYP7A1; JNK; TNF-α; cholesterol; perinatal nutrition

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