Use of the fetal reprogramming of a PPAR delta agonist
A technology of reprogramming and agonist, applied in the direction of medical preparations containing active ingredients, applications, animal feed, etc.
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Embodiment 1
[0170] Mouse fetal reprogramming using PPARδ agonist
[0171] To study the role of PPARδ in fetal reprogramming during mammalian development, the inventors used a method of administering a PPARδ agonist to a pregnant mother (maternal treatment). For fetal reprogramming, at a concentration of 10 mg / kg per day ( concentration) Orally administered PPARδ agonist to pregnant mice, in figure 1 The specific experimental methods are summarized in .
[0172] (1) Confirm whether PPARδ agonists pass through the placenta
[0173]Pharmacokinetic experiments were performed to confirm whether the PPARδ agonist (CMDD1111) used in this study crossed the placenta. CMDD1111 was administered to mice on day 16 of gestation at a concentration of 10 mg / kg, after which the concentration of the compound distributed in the blood of the mother animals and fetuses was analyzed for 24 hours. As a result, the maximum plasma concentration of the compound (C max ) is 38μM, the time to reach its maximu...
Embodiment 2
[0176] Verification of the effect of slow muscle fiber increase in mice subjected to fetal reprogramming through PPARδ activation
[0177] Slow-twitch fibers have a lot of myoglobin (which is an oxygen transport protein) and therefore appear redder than fast-twitch fibers. When the skin of the fetus was removed and its muscles observed, it could be seen that the administered mouse group had redder muscles ( Figure 7 A and 7B). To confirm whether slow-twitch fiber production was increased due to the administration of the substance (CMDD1111), the hind legs of mice were excised and then frozen in OCT. The frozen muscle tissue was cut into 8 mm thick sections by using a cryostat, mounted on glass slides, after which the sections were subjected to metachromatic staining. Slow-twitch fibers are stained a darker blue than fast-twitch fibers by metachromatic staining. Such as Figure 7 C It can be confirmed that dark blue myofibers are increasingly produced in the gastrocnemius...
Embodiment 3
[0178] Verification of the increasing effect of slow muscle fibers regulated by calcium ions
[0179] The present inventors performed gene expression analysis to determine the cause of the increased slow-twitch fiber production in mice subjected to fetal reprogramming activated by PPARdelta.
[0180] (1) Gene expression analysis using microarray
[0181] Regarding the animals, the gastrocnemius muscle of 3-week-old mice fetally reprogrammed by a PPARδ agonist (CMDD1111) was excised, after which total RNA was extracted by using Trizol reagent (Gibco). The isolated RNA was subjected to a quantification and purification verification process before being used for gene expression analysis using a Mouse4302.0 (Affimatrix) chip.
[0182] In general, slow-twitch fibers have more mitochondria, increased fatty acid oxidation, and lower contraction rates than fast-twitch fibers. From the analysis results, it was confirmed that the expression of all genes related to the above three typ...
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