THE INFLUENCE OF IMMUNIZATION OF RATS WITH BSA-CONJUGATED PEPTIDE 269280
OF TYPE 3 MELANOCORTIN RECEPTOR ON THE METABOLIC PARAMETERS
AND THYROID FUNCTIONS
K.V. Derkach,1 E.A. Shpakova,2 O.A. Zharova,3 V.M. Bondareva,1 A.O. Shpakov 1,*
1 I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry RAS,
2 Institute of Macromolecular Compounds RAS, St. Petersburg,
and 3 Pharmaceutical Company OOO «Teva», Yaroslavl;
* e-mail: alex_shpakov@list.ru
One of the approaches to study the role of the brain hormonal signaling systems in the regulation of biochemical
and physiological processes is their shutdown using the antibodies generated to peptides corresponding to
extracellular regions of receptors. The brain type 3 melanocortin receptors (M3R) play an important role in the
central regulation of the metabolism and the endocrine system. However, the influence of prolonged inhibition
of M3R on energy metabolism, insulin resistance, and thyroid gland (TG) function is practically not studied.
The aim of the study was to investigate the influence of prolonged repeated immunization of male rats with the
BSA-conjugated peptide Ala-[Pro-Thr-Asn-Pro-Tyr-Cys-Ile-Cys-Thr-Thr-Ala-His269280]-Ala (A[269
280]A) corresponding to the third extracellular loop of M3R on their metabolic parameters and functional activity
of TG. 9 months after the first immunization, the weight of rats was reduced and after 1213 months was
significantly lower than in controls. The weight of abdominal and brown adipose tissues, on the contrary, increased.
At the same timeline there was an increase in the fasting glucose and insulin levels, and increase of the
HOMA-IR index (by 75 %) indicating that immunized animals develop insulin resistance. The rats have increased
glucose utilization due to an increase of insulin production by pancreatic β-cells. 12 months after the first
immunization, the increase of the triglycerides level (by 74 %) and the ratio of LDL- and HDL-cholesterol (by
36 %) were revealed. 13 months after the start of immunization, the levels of free and total thyroxine and total
triiodothyronine significantly decreased. In the TG plasma membranes of immunized rats the weakening adenylyl
cyclase stimulating effect of thyroid-stimulating hormone was detected. Thus, long-term decrease in the brain
M3R activity due to repeated immunization of rats with BSA-conjugated peptide A[269280]A induces the
disturbances of the peripheral metabolism and TG function.
Key words:
adenylyl cyclase, dyslipidemia, insulin resistance, type 3 melanocortin receptor, peptide,
thyroid hormone, glucose tolerance, the third extracellular loop, thyroid
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