A novel follicle-stimulating hormone vaccine for controlling fat accumulation

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 FSH beta (FSH beta 13AA) was indentifled to be the FSH receptor-binding epitope in both humans and mice. By conservation analysis, we found such FSH beta 13AA is highly conserved across species. Accordingly, we designed a new FSH antigen by synthesizing a tandem of FSH beta 13AA (LVYKDPARPNIQK) and then conjugating it to ovalbumin (FSH beta 13AA-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 PPAR gamma 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 beta-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. (C) 2020 Elsevier Inc. All rights reserved.