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. / published_or_final_version / Biological Sciences / Master / Master of Philosophy
| Identifer | oai:union.ndltd.org:HKU/oai:hub.hku.hk:10722/182277 |
| Date | January 2012 |
| Creators | Yeung, Oi-yee., 楊藹怡. |
| 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/B47752671 |
| 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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