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Using anti-adipocyte monoclonal antiboies for controlling the development of adipose tissue. Dr. Ziad Jaradat.
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Using anti-adipocyte monoclonal antiboies for controlling the development of adipose tissue. Dr. Ziad Jaradat
Polyclonal antibodies have been raised against fat cells or adipocyte plasma membrane proteins of rats, rabbits, pigs… etc. studies in rats showed that injection of anti-adipocyte polyclonal antisera resulted in long term reduction of the number of adipocyte in internal fat depots probably due to adipocyte lysis.
A decrease in total body fat as well as of dorsal and perirenal adipose tissues was obtained in experimental rabbits. In sheep, several fat depots (i.e backfat, subcutaneous, omental (One of the folds of the peritoneum that connect the stomach with other abdominal organs) , perirenal and kidney pelvic) were reduced after injection of antisera against adipocyte plasma membranes.
However, these experiments did not show out obvious improvement of carcass production. In contrast, in porcine such anti-sera led to a long term fat reduction and to an increase in lean carcass development.
Drawback; the anti-sera is not specific, so absorption with extracts of none adipose tissue is the method to increase their specificity, however, this method is laborious and expensive.
Therefore, a monoclonal antibody would be the ultimate goal. A highly specific monoclonal antibody for fat cell surface proteins has been produced.
Experimental • Treatment of young piglets with anti-adipocyte monoclonal antibody. • Monoclonal antibody preparation was injected intraperitoneally in young large white pigs two and 5 days after birth. Pigs were sacrificed 38 days after birth, and various tissues were analyzed. Heart, spleen and liver were not affected, whearase all the adipose tissue were slightly decreased in weight.
The back fat and subcutaneous ham adipose tissue reached the most significant reductions. In addition, adipocyte were small in size than the control one. Finally the total amount of lipid in the carcass was significantly decreased without affecting other organs or tissues.
When the monoclonal antibody was injected into five day old piglets and were left to reach 50-100 kg body weight, it appeared that the subcutaneous layer in the pigs was less as well as the adipose tissue in the shoulder, back fat and the kidney area without affecting the gross carcass weight.
Immunocastration of farm animals • Traditional castration generates stress to the animals and decreasing their efficiency. Therefore, it is important to find a none-invasive alternative. • Immunization against sex hormones such as LHRH, LH, FSH, and HCG can affect reproduction therefore, these hormones were the target of immunocastration. Immunization against gonadal steroids, ova and sperm were also considered.
Immunization against LHRH • LHRH is the first intracellular messenger of the control of fertility. Immunological neutralization of LHRH would expect to block pituitary secretion of LH and FSH and will lead to gonadal quiescence.
In lambs, the immunnutralisation reduced testis weight and the concentration of testosterone in serum which also reduced sexual behavior. • Likewise, immunization of heifers against LHRH lead to reduction of fertility equivalent to that of ovariectomized heifer.
However the effect of this vaccine is reversible and subsequent fertility was normal. A vaccine against LHRH is commercialized under the name Vaxstrate and is available in Australia. What happens is that the administration of the vaccine suppresses ovarian cyclicity in post pubertal females for a period of six to eight months.
After this time the effect of the vaccine disappears and the ovarian function returns to normal. To make the vaccine more efficient, it could be administered with adjuvants which prolong its effect.
Another vaccine in the market is called Improvac, which was used mainly in pigs also produced positive results and pigs treated with this vaccine grew more rapidly producing heavy boars with improved meat quality through the prevention and control of boar taint (spoilage and diseases).
Immunization against gonadal steroids • Anti-progestrone monoclonal antibody completely blocked pregnancy. The action of antibody in females was associated with a failure to initiate an implantation response. The most pronounced effect, however, was a break of embryonic development at a stage prior to cavitation.
Passive immunization against progesterone shortly after mating interferes with early hormone dependent steps which are essential for normal embryonic development. • In contrast, immunization against testosterone was not characterized by inhibition of sexual behavior in rams and there was no suppression of testicular function.
Sperm and Ova antigens • Antibodies made against sperm or ova will block gamete interactions required for fertilization. Zona pelluida forms a coating around mammalian eggs. • The ZP is comprised essentially of three major glycoproteins which are involved in sperm binding during their penetration through the zona.
ZP3 was identified as a major sperm receptor as was targeted as most likely female gamete antigen for a contraceptive vaccine. In several species immunization of females against ZP antigens can lead to control of fertility.
Now sperm antigens can be used to immunize males or females while ZP antigens are effective only in females.
