Offsetting the impacts of maternal and postnatal overnutrition: effects of maternal green tea extractsupplementation on expression of central metabolic regulators inoffspring

Abstract

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.