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A novel follicle-stimulating hormone vaccine for controlling fat accumulation

Author:
Han, Xingfa, Guan, Zichao, Xu, Miaomiao, Zhang, Ying, Yao, Huan, Meng, Fengyan, Zhuo, Yong, Yu, Guozhi, Cao, Xiaohan, Du, XiaoGang, Bu, Guixian, Kong, Fanli, Huang, Anqi, Zeng, Xianyin
Source:
Theriogenology 2020 v.148 pp. 103-111
ISSN:
0093-691X
Subject:
adipocytes, adipose tissue, adjuvants, amino acids, animal models, antibodies, biosynthesis, blood serum, body weight changes, epitopes, females, follicle-stimulating hormone, humans, lipids, males, mice, obesity, ovalbumin, ovariectomy, peroxisome proliferator-activated receptor gamma, signal transduction, vaccination, vaccines
Abstract:
Follicle-stimulating hormone (FSH) has been newly demonstrated to play a great role in promoting fat accumulation, providing a potential to target FSH for controlling fat accumulation and treating obesity. A short, 13-amino acid of FSHβ (FSHβ13AA) was indentified to be the FSH receptor-binding epitope in both humans and mice. By conservation analysis, we found such FSHβ13AA is highly conserved across species. Accordingly, we designed a new FSH antigen by synthesizing a tandem of FSHβ13AA (LVYKDPARPNIQK) and then conjugating it to ovalbumin (FSHβ13AA-T-OVA). Then, we tested its efficacy in suppressing fat accumulation in both ovariectomized and intact mouse models. Vaccination with this novel antigen emulsified in mild adjuvant, Specol, was highly effective in preventing ovariectomy-induced body weight gain and fat accumulation in mice (P < 0.01). Mechanistically, FSH vaccination treatment inhibited lipid biosynthesis by inactivating PPARγ adipogenic signaling pathway and simultaneously enhanced adipocyte themogenesis via upregulating UCP1 expression in both visceral and subcutaneous adipose tissues. Moreover, injection of this novel FSH vaccine also substantially reduced (P < 0.05) fat accumulation in both intact male and female mice. These actions result from the specific binding of the generated antibody to the β-subunit to block its action, rather than lowering the circulating levels of FSH, as evidenced by nearly no alterations in serum FSH levels in mice following FSH vaccination. Overall, we developed a novel FSH antigen and vaccine, and demonstrated it is highly efficacious in suppressing fat accumulation.
Agid:
6855772