The Depot-specific Androgen-like Effects of Wild Bitter Gourd on the Adipose Tissues of Orchidectomized Mice

Autor: Yu-Jen Wang, 王昱仁
Rok vydání: 2018
Druh dokumentu: 學位論文 ; thesis
Popis: 106
It has been shown that androgen status can affect white adipose tissues (WAT) through the cognate receptor, androgen receptor (AR). Although epidemiological and clinical studies observed an association between metabolic disorder and hypogonadism, conflicting results have been reported in animal studies. Previous results in our lab showed that bitter gourd extract interacted with AR in vitro. This experiment was designed to examine effects of wild bitter gourd powder (lyophilized whole fruit powder of Momordica Charantia, BGP) on various WAT depots in androgen deficiency using the orchidectomized mouse model. Male C57BL/6J mice were sham-operated or castrated and fed a high sucrose diet (HS, modified from AIN-93G comprising 50% w/w sucrose). Castrated mice were supplemented without (Cast) or with 5% BGP (Cast+BGP) or 0.007% testosterone propionate (Cast+TP). After 23 weeks of feeding, the Cast+BGP group had significantly lower body weight than Sham and Cast groups, and the latter two groups did not differ. The Cast+BGP group also showed significantly lower RWAT and IWAT weights (absolute and relative) compared to the Cast group. Cast+BGP and Cast+TP groups had significantly lower feed efficiency and energy efficiency compared to Sham and Cast groups. Sham mice had significantly higher serum triglyceride (TG) than the Cast group, while the Cast+BGP group showed significantly lower TG than Sham and Cast+TP groups. Cast, Cast+BGP, and Cast+TP groups had comparable serum insulin and total cholesterol levels, which were significantly lower than those of the Sham group. The Sham group had significantly higher AR downstream gene expressions, especially Fkbp5, than that of the Cast group in all three WAT depots. The mRNA expressions of Srebf1 and Cd36 also tended to follow androgen status and showed higher level in the Sham group than in the Cast in all depots. The mRNA expressions of Fkbp5, Srebf1, Cd36 in the RWAT and that of Ar, Igf1, Srebf1, Cd36 in EWAT of the Cast+BGP group were comparable to those of the Sham group. In RWAT and IWAT, Ccl2 mRNA expression was significantly higher in the Sham group than in the Cast group, but higher IL6 and IL10 mRNA expressions in Sham group than in Cast group were only observed in RWAT. BGP exerted different effects on different depots. While the Cast+BGP group had significantly higher Fkbp5 mRNA expression in RWAT, this group showed down-regulation of this gene in IWAT, compared to the CAST group. BGP up-regulated TNFα, IL6, IL4 and IL10 mRNA expressions only in RWAT but not other depots. Ucp1 mRNA was up-regulated only in the IWAT of the Cast+BGP, compared to the Sham group, implying enhanced browning in this depot. On the other hand, Ucp2 mRNA of RWAT was up-regulated in the Cast+BGP group to a level comparable to that of the Sham group. As for adipogenic genes, the Cast+BGP group showed significantly higher mRNA expressions of Cebpα in RWAT and Pparγ in EWAT than those of the Cast group. This group also had significantly lower mean adipocyte sizes than Cast group. In conclusion, androgen deficiency and dietary BGP supplementation showed depot-specific impacts on mRNA expressions of genes related to AR signaling, adipogenesis, lipid metabolism and inflammation in the white adipose tissues. Based on our results, some of the BGP effect might be through AR, but others might not.
Databáze: Networked Digital Library of Theses & Dissertations
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