Synergistic effect of arcuate and raphe nuclei graft to alleviate insulinemia and obesity in Zucker rats

The arcuate nucleus (AN) of the hypothalamus is a key area in which endocri ne messages are relayed to the brain, while midbrain raphe nucleus (RN) is the source of brain serotonin. Both nuclei contribute to the central mechan ism of energy homeostasis. This experiment aimed to determine the impact of AN and RN grafts on insulinemia and obesity in diabetic rats. AN and RN we re dissected from 15-day (Fa/Fa) lean embryos and grafted separately or tog ether into the third brain ventricle of obese (fa/fa) male Zucker rats. His tological analysis showed the functional maturity of grafts, which were vas cularized, contained neurons reinnervating the periventricular hypothalamus and hypophysis, and expressed neuropeptide Y and enzymes for dopamine and serotonin synthesis. Three months after transplantation, the rats grafted w ith AN or RN had a lower body weight gain compared to sham-operated rats (1 9% and 17%, respectively). Rats grafted with AN together with RN gained sig nificantly less body weight than rats grafted with AN or RN separately (31% vs. sham-operated rats), and showed a decreased plasma insulin concentrati on (132 +/- 33 muU/ml) vs. sham-operated rats (459 +/- 108 muU/ml, p < 0.05 ). A synergistic effect on alleviating obesity and insulinemia by double AN and RN grafts suggests that both these nuclei are functionally interrelate d in maintaining energy homeostasis, and normal functioning of both nuclei is altered during obesity.