Development of obesity in transgenic rats with low circulating growth hormone levels: involvement of leptin resistance.
BACKGROUND
Human growth hormone (hGH) transgenic (TG) rats have been produced in our laboratory. These TG rats are characterized by low circulating hGH levels, virtually no endogenous rGH secretion, and massive obesity.


OBJECTIVE
To elucidate how energy balance and leptin sensitivity contributed to the establishment of this obesity.


METHODS
Food intake, locomotor activity and leptin concentrations in serum and cerebrospinal fluid were measured in TG rats and their non-transgenic littermates (control). The effect of intraperitoneal and intracerebroventricular injection of leptin on food intake and body weight gain was also examined.


RESULTS
An increase in food intake and a decrease in locomotor activity were observed from 4 and 7 weeks of age, respectively, in the transgenic rats compared with control. Serum leptin concentrations of the transgenic rats were more than twice as high as those of control rats and were associated with an increased white adipose tissue mass and ob gene expression. Intraperitoneal injection of leptin significantly decreased food intake and body weight gain in control rats, but not in transgenic rats. Leptin concentration in the cerebrospinal fluid of transgenic rats was not different from that of control rats, and intracerebroventricular injection of leptin was similarly effective in reducing food intake and body weight gain as it was in control rats.


CONCLUSIONS
These results suggest that the transgenic rats, whose GH secretion is suppressed, develop obesity due to early onset of an increase in food intake and a decrease in locomotor activity with leptin resistance resulting from deteriorating leptin transport from peripheral blood to cerebrospinal fluid.
Furuhata
Y
Y
Department of Veterinary Physiology, Veterinary Medical Science, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Kagaya
R
R
Hirabayashi
K
K
Ikeda
A
A
Chang
K T
KT
Nishihara
M
M
Takahashi
M
M
D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D015152:Blotting, Northern; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005786:Gene Expression Regulation / Q000502:physiology; D019382:Human Growth Hormone / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D006801:Humans; D020738:Leptin / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009765:Obesity / Q000503:physiopathology*; D051381:Rats
D020738:Leptin; D019382:Human Growth Hormone