Pathophysiological Significance of the<i>Obese</i>Gene Product, Leptin, in Ventromedial Hypothalamus (VMH)-Lesioned Rats: Evidence for Loss of Its Satiety Effect in VMH-Lesioned Rats<sup>1</sup>
EndocrinologyPublished 1 March 1997
Noriko Satoh, Yoshihiro Ogawa, Goro Katsuura, Tetsuo Tsuji, Hiroaki Masuzaki, Junko Hiraoka
Citations141
SJR quartileQ1
SJR score1.31
SNIP1.01
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TL;DR
Evidence is provided that VMH-lesioned rats overproduce leptin and increase its release but cannot respond to it and it is suggested that the loss of its satiety effect contributes to the development of obesity and the obesity-related phenotypes in VMH.
Abstract
To explore the pathophysiological significance of the obese (ob) gene product, leptin, in ventromedial hypothalamus (VMH)-lesioned rats, we examined the synthesis and secretion of leptin and its satiety effect in VMH-lesioned rats compared with those in sham-operated rats. Northern blot analysis revealed that ob gene expression is markedly augmented in the mesenteric and sc white adipose tissue, but remained unchanged in the epididymal white adipose tissue during the development of obesity in VMH-lesioned rats. Plasma leptin levels were relatively constant in sham-operated rats, but were elevated during the development of obesity in VMH-lesioned rats. In sham-operated rats, a single i.v. (1.0 mg/rat) or intracerebroventricular (2.0 micrograms/rat) injection of recombinant human leptin reduced food intake and body weight gain in sham-operated rats. By contrast, no significant effect on food intake or body weight gain was observed in VMH-lesioned rats. The present study provides evidence that VMH-lesioned rats overproduce leptin and increase its release but cannot respond to it and suggests that the loss of its satiety effect contributes to the development of obesity and the obesity-related phenotypes in VMH-lesioned rats.
Keywords
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