5.1 Overall Discussion and Conclusions
5.1.4 Recommendation for Future Research
Based on the findings of the current series of studies, recommendation for future research are
Yizhen Wu 103 listed as follows:
1. In the current study treatment of obese mice with Rb1 restored leptin induced activation of STAT3 phosphorylation, but not phosphorylation of FOXO1 in the mediobasal hypothalamus.
Therefore, in the hypothalamus, Rb1 acted on the STAT3 signaling pathways rather than the FOXO1 pathway to restore leptin signaling and sensitivity. The precise mechanisms need further examination.
2. In the current study, we demonstrated Rb1 elevated circulating PYY in the treated obese mice. PYY is a gut-brain anorexigenic hormone that promotes negative energy balance by reducing appetite (Boey et al., 2008). The increased plasma PYY in Rb1 treated obese mice may have contributed to the negative energy balance, lower body weight gain and fat accumulations in these animals. The mechanism by which Rb1 treatment increased circulating PYY levels requires to be further determined.
3. This study demonstrated that Rb1 increased leptin sensitivity in the prefrontal cortex of obese mice, and in prefrontal cortical neurons treated with palmitic acid, as well as reversed the alterations of leptin downstream signaling molecules (pJAK2, STAT3, BDNF, and PSD95).
However, further study needs to be carried out to determine if Rb1 directly interacts with the leptin receptor.
4. This study illustrated that Rb1 treatment ameliorated alteration of leptin-JAK2-STAT3 and leptin-BDNF in the prefrontal cortex of obese mice and improves hyperleptinemia. Rb1 treatment also promoted leptin’s effect on neurite branching and elongation, and synaptogenesis in prefrontal cortical neurons. As high-fat diet-induced obesity has been implicated in the progression of neurodegenerative diseases, such as vascular dementia. Rb1treatent may have therapeutic effects in attenuating the progression of cognitive declines in obese patients and reducing the risk of neurodegenerative diseases. This will be the next work to further validate using obese mice model.
5. This study presented teasaponin improved leptin sensitivity in the prefrontal cortex of obese mice and primary cortical neurons treated with palmitic acid, and reversed the alterations of leptin downstream signaling. According to the amphiphilic nature and able to intercalated into
Yizhen Wu 104 the plasma membrane, replacing membrane cholesterol and increasing membrane fluidity, and thus this molecule could change the immediate environment of cell membrane proteins.
However, it is required to further investigate if teasaponin directly interacts with the leptin receptor.
6. This study present oral teasaponin improved the recognition memory in treated obese mice.
Since high fat diet-induced obesity has been implicated in the progression of neurodegenerative diseases, such as vascular dementia, teasaponin supplementation may have beneficial effects in attenuating the progression of cognitive decline in obese patients and reducing the risk of neurodegenerative diseases. However, the eventual toxicicity of long-lasting exposition to elevated concentrations of teasaponin should be examined before teasaponin supplementation to be recommended.
Yizhen Wu 105
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Dendritically targeted Bdnf mRNA is essential for energy balance and response to leptin. Nat
Dendritically targeted Bdnf mRNA is essential for energy balance and response to leptin. Nat