The overall objective of this thesis was to test the hypothesis that through developmental programming maternal overnutrition-induced metabolic derangements in the offspring could be offset by supplementing the maternal diet with green tea epigallocatechin gallate (GTEG).
The obesogenic diet was a high-fat (HF, 30%) diet. Female Sprague-Dawley rats were fed the HF, low-fat (LF, 7%) or HF diet containing 0.75% or 1.0% GTEG (GT1, GT2) from before conception and throughout gestation and lactation. Both doses of GTEG significantly improved metabolic control of the HF-fed lactating dams. The weaned male pups received the HF, GT1 or GT2 diet forming 6 dam/pup groups: LF/HF, HF/HF, HF/GT1, HF/GT2, GT1/HF and GT2/HF. At wk 13 they had similar weight but insulin resistance index (IRI), serum non-esterified fatty acid (NEFA) and liver triglyceride of rats born to GTEG dams was 57, 23 and 26% lower and accompanied by improved gene/protein expressions related to lipid and glucose metabolism compared to HF/HF rats (P < 0.05). Although the HF/GT1 and HF/GT2 rats had lower serum NEFA, their serum insulin and IRI remained comparable with the HF/HF rats.
To determine if there is a critical time period for the actions of GTEG, in the second experiment female rats were fed the LF, HF, or GT1 diet prior to conception and throughout gestation. During lactation, half of the dams had their diet switched from HF to GT1 and vice versa. Pups were weaned to the HF or LF diet, forming the LF/LF/LF, LF/LF/HF, HF/HF/LF, HF/HF/HF, HF/GT1/LF, HF/GT1/HF, GT1/GT1/LF, GT1/GT1/HF, GT1/HF/LF and GT1/HF/HF groups. Metabolic controls of dams given GT1 during gestation or lactation were improved compared with the HF/HF dams (P < 0.05). Three-way ANOVA revealed that 22 wk old offspring born to dams fed the HF diet during gestation had higher serum and muscle triglyceride (TG) concentration and lower ferric reducing ability of plasma (FRAP) (P < 0.05), all of which were reversed by supplementing GT1 to the gestational diet. Oral glucose tolerance at wk 15 was improved in those offspring born to dams given GT1 supplementation during lactation (P < 0.05). The increased serum NEFA concentration and IRI in offspring of dams fed the HF diet during gestation or lactation were reversible upon GT1 supplementation during either time period (P < 0.05). These rats (HF/GT1/HF, GT1/GT1/HF and GT1/HF/HF) had similar level of hepatic insulin receptor gene expression as well as protein abundance for muscle glucose transporter 4 and hepatic sterol regulatory element binding protein-1c but lower protein mass for hepatic glucose-6-phosphatase (P < 0.05) compared with the LF/LF/HF rats.
Hence, maternal overnutrition-induced metabolic derangements in male offspring are reversible through supplementing GTEG to the maternal diet during gestation or lactation and this approach is more effective than giving GTEG to offspring born to overnourished mothers. Offspring metabolism could be programmed via manipulations of the maternal diet. / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy
| Identifer | oai:union.ndltd.org:HKU/oai:hub.hku.hk:10722/180056 |
| Date | January 2012 |
| Creators | Li, Shiying, 李诗盈 |
| Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
| Source Sets | Hong Kong University Theses |
| Language | English |
| Detected Language | English |
| Type | PG_Thesis |
| Source | http://hub.hku.hk/bib/B47156132 |
| Rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works., Creative Commons: Attribution 3.0 Hong Kong License |
| Relation | HKU Theses Online (HKUTO) |
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