Transplantation of lean fetal hypothalamus reduces the hyperphagia,
hyperlipidemia and hyperinsulinemia of zucker obese rats.
Fukagawa, Koji, David S. Knight, Hugh V. Price, Toshiie Sakata, and
Patrick Tso.
Department of Physiology, and Department of Anatomy, Louisiana
State University Medical Center, Shreveport, Louisiana, 71130 U.S.A.,
First Department of Internal Medicine, Oita Medical University, Oita,
879-55 Japan
APStracts 3:0042R, 1996.
Rats with lesions to the ventromedial hypothalamus (VMH) manifest
obesity, hyperphagia and hyperinsulinemia and fetal VMH
transplantation into the third cerebroventricle of VMH-lesioned rats
reduces the development of obesity caused by the lesion. The aim of
this study was to determine whether the hyperphagia, hyperlipidemia
and hyperinsulinemia of obese Zucker rats could be corrected by the
transplantation of lean fetal Zucker hypothalamic tissue into the
third cerebral ventricle of Zucker obese rats. Following the fetal
hypothalamic transplant (Obese-HY), the rate of weight gain was
significantly diminished compared to the unoperated Zucker obese rats
(Obese) and the obese rats that received the transplantation of a
similar amount of frontal cortical tissue from the same fetus (Obese
-FC). Food intake was significantly lower, and plasma triacylglycerol
and insulin concentrations were also significantly reduced in the
Obese-HY rats compared to the Obese and Obese-FC rats. The weight of
the adrenal glands, the plasma ACTH concentration, the liver weight
and the liver lipid content in Obese-HY were significantly less than
those observed in the Obese and Obese-FC animals. There were no
significant differences between the Obese and the Obese-FC animals or
between Lean (unoperated Zucker lean rats) and Lean-HY rats (Lean
rats transplanted with lean fetal hypothalamus) in all the parameters
we determined in this study. Neovascularization and normal cellular
morphology of the transplanted fetal hypothalamic tissue suggest that
the transplanted neural and glial cells were viable and
physiologically functional. In conclusion, this study offers evidence
suggesting that the hypothalamic-pituitary-adrenal function is
defective in Zucker obese rats, resulting in excessive weight gain,
hyperphagia, hyperlipidemia and hyperinsulinemia. The hypothalamic
dysfunction in the Zucker obese rats is corrected by the
transplantation of lean fetal hypothalamus.
Received 9 June 1994; accepted in final form 29 January 1996.
APS Manuscript Number R318-4.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 14 February 96