The relationship between fructose consumption and metabolic
diseases has drawn substantial attention in recent years. Dietary fructose
consumption has climbed dramatically in the past 40 years, and this trend
coincides with the prevalence of obesity and diabetes worldwide. In
rodents, maternal obesogenic diets are associated with higher risks of
metabolic derangement later in life whereas bitter melon (BM)
supplementation has been shown to improve blood glucose and lipid
profiles. The overall objective of this thesis was to test the hypothesis that
through developmental programming metabolic derangement in offspring
born to rat dams fed a high-fructose (F) diet could be offset by the addition
of BM to the maternal diet.
Virgin female rats received a control (C), F (60%) or BM-supplemented
F (FBM,1%) diet 8 weeks before conception and throughout gestation and
lactation. Weaned male offspring consumed C diet (C/C,F/C,FBM/C) for 11
weeks. The concentrations of serum insulin, triglyceride, free fatty acid
(FFA), and hepatic lipids in FBM/C offspring matched that in C/C offspring
and were significantly lower than F/C offspring. These phenotypic changes
were accompanied with suppressed hepatic lipogenic gene expression but
enhanced expression of lipid oxidation-related genes.
In the second experiment, we extended the earlier findings by
examining whether adding BM to F-fed dams would still benefit offspring if
they continued to consume the F diet postweaning. This simulates the
scenario in affluent societies where fructose overconsumption may occur in
two consecutive generations. The dose-response effect of BM at doses of
0.85% (FBM1) and 1% (FBM2) was also examined. Male offspring born to
dams fed the C, F, FBM1 or FBM2 diet were weaned to C or F diet
(C/C,C/F,F/F,FBM1/F,FBM2/F) for 20 weeks. BM normalized the serum
FFA elevation observed in F/F offspring, although hyperinsulinemia
remained in FBM1/F and FBM2/F offspring. The altered liver lipid profile
and its molecular changes observed in F/F offspring were ameliorated by
maternal BM supplementation. Lower adipose expression of
mesoderm-specific transcript, hormone sensitive lipase, sterol regulatory
element-binding transcription factor 1, and peroxisome
proliferator-activated receptor-gamma (PPARγ) and PPARγ-target genes in
FBM1/F and FBM2/F offspring indicated that BM could reduce adipocyte
size as well as lower lipolysis and lipogenesis.
Since FFA stimulates reactive oxygen species generation that
enhances cellular stress, oxidative stress and inflammation in offspring of
two-generation F exposure with or without maternal BM supplementation
were examined. FBM1/F and FBM2/F offspring showed reduced lipid
peroxidation but enhanced antioxidant capacity in the liver. BM suppressed
the expression of proinflammatory genes and phosphorylation of c-Jun
amino terminal kinase1, as well as promoted insulin receptor substrate 1
protein expression. These BM-mediated antioxidant and anti-inflammatory
effects may be associated with a reduction of circulating FFA.
Taken together, the data support the concept of developmental
programming as maternal fructose clearly induced dyslipidemia, adipocyte
dysfunction, oxidative stress and inflammation in offspring. That these
abnormalities were largely reversed by adding BM to the maternal diet
suggests that perinatal BFC supplementation could alter the course of
maternal malnutrition-induced metabolic defects later in life. / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy
| Identifer | oai:union.ndltd.org:HKU/oai:hub.hku.hk:10722/180926 |
| Date | January 2012 |
| Creators | Ching, Hiu-ha., 程曉霞. |
| 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/B47752555 |
| 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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