Abstract
Following the chemically-induced lesion of the ventromedial nucleus, gold-thioglucose treated rodents display hypothalamic leptin resistance, hyperphagia, hyperinsulinemia and obesity. Despite the exuberant hyperinsulinemia following gold-thioglucose treatment, systemic insulin sensitivity is preserved during the early phase of the obesity syndrome, resulting in extensive fat production and markedly increased leptin levels. Leptin and adiponectin levels are inversely associated in vivo . However, the reciprocal relationship between leptin and adiponectin can not be explained by in vitro observations, suggesting the involvement of the central nervous system. We measured leptin and adiponectin expression levels in gold-thioglucose obese and control mice. In this study, we show that gold-thioglucose treatment causes a profound reduction in the number of hypothalamic glucokinase transcripts in rodents. Also, we demonstrate that the adiponectin expression levels and protein content are increased in gold-thioglucose treated animals, which can explain the increased insulin sensitivity during the early phase of the obesity syndrome. Furthermore, as the increased leptin production in gold-thioglucose obese mice is not paralleled by reduced adiponectin production, our data suggest that the inverse regulation between leptin and adiponectin levels is, at least partially, mediated via the hypothalamus.
Key words
Adipokines - leptin - hypothalamus - adipose tissue - insulin sensitivity
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Correspondence
P. Huypens
Diabetes Research Center·Vrije Universiteit Brussel
Laarbeeklaan 103·1090 Brussels·Belgium
Phone: +32/2/477 44 71
Fax: +32/2/477 44 72
Email: Peter.Huypens@vub.ac.be