- 學位論文
Offsetting the impacts of maternal and postnatal overnutrition: effects of maternal green tea extractsupplementation on expression of central metabolic regulators inoffspring
Offsetting the impacts of maternal and postnatal overnutrition: effects of maternal green tea extractsupplementation on expression of central metabolic regulators inoffspring
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並列摘要
The overall objective of this thesis was to test the hypothesis that maternal overnutrition has adverse effects on the expression of central metabolic regulators in offspring but could be offset by supplementing green tea extract (GTE) to the dams during gestation and/or lactation. This thesis focuses on two aspects of central metabolic regulation: the leptin signaling that links to appetite regulation and the sirtuin 1(SIRT1)/oxidative stress pathway that links to insulin sensitivity (IS). This study was initiated based on previous findings of this laboratory that via developmental programming energy intake of offspring born to dams given GTE during lactation was suppressed and that IS was improved in offspring of dams supplemented with GTE during gestation and/or lactation. The diets used included low fat (LF), high-fat (HF), and HF diet added with 0.75% or 1%GTE (GT1, GT2). In experiment 1, female rats were given the respective diet 8 weeks prior to mating till the end of lactation. Male offspring were weaned to the HF, GT1 or GT2 diet for 10 weeks forming the LF/HF, HF/HF, GT1/HF, GT2/HF, HF/GT1 and HF/GT2 groups. Maternal and postweaning GTE supplementation increased hypothalamic leptin receptor (OB-Rb) and signal transducer activator of transcription 3 (STAT3) mRNA suggestive of enhanced leptin signaling but pro-opiomelanocortin (POMC) mRNA expression, an appetite inhibitor was only elevated in the HF/GT1 group which was associated with reduction in food intake in this group. Central oxidative status was improved in GT1/HF and GT2/HF offspring through enhanced hypothalamic SIRT1 and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) expression compared with the HF/HF group. These improvements coincided with better IS in the HF offspring born of GTE supplemented dams. Experiment 2 was designed to determine the relative importance of gestation and lactation as the critical period for GTE supplementation. Female rats were assigned to LF, HF or GT1 diet 9 weeks prior to mating till the end of pregnancy. During lactation half of the HF and GT1 dams had the diet switched to GT1 and HF, respectively. Male offspring were fed the LF or HF diet until 22 weeks of age forming 10 offspring groups: LF/LF/LF, LF/LF/HF, HF/HF/LF, HF/HF/HF, HF/GT1/LF, HF/GT1/HF, GT1/HF/LF, GT1/HF/HF, GT1/GT1/LF, and GT1/GT1/HF. Consistent with a reduction in energy intake in offspring born to dams receiving GTE supplementation during lactation, there was an increase in melanocortin 4 receptor (MC4R) expression in the hypothalamus (P<0.05). Regardless of postweaning diet, offspring of dams given GTE during gestation and/or lactation had elevated hypothalamic PGC-1α and reduced protein phosphorylation of c-Jun N-terminal kinase-1 when compared with offspring of unsupplemented dams(P<0.05) which was associated with improved IS. Hence, leptin signaling and appetite regulators in the offspring were selectively affected by GTE supplementation during lactation whereas offspring exhibited improved ability to handle oxidative stress if dams received GTE supplementation during gestation and/or lactation. Collectively, these results support the notion that central mechanisms with roles in appetite control and oxidative status are susceptible to the programming phenomenon triggered by maternal nutritional status.