Vanadium, a potent nonselective inhibitor of
protein tyrosine phosphatases, has been shown to mimic many of the metabolic actions of
insulin both in vivo and in vitro. The mechanism(s) of the effect of
vanadium on the decrease in appetite and
body weight in Zucker fa/fa rats, an
insulin-resistant model, is still unclear. Because
insulin may inhibit hypothalamic
neuropeptide Y (NPY), which is known to be related to appetite, and increase
leptin secretion in adipose tissue, we studied the possibility that the changes in appetite produced by
vanadium may be linked to altered NPY levels in the hypothalamus. We also examined effects of
vanadium on
leptin. Zucker lean and fatty rats were chronically treated with
bis(maltolato)oxovanadium(IV) (BMOV), an organic
vanadium compound, in the
drinking water. Plasma and adipose tissue
leptin levels were measured by radioimmunoassay and immunoblotting, respectively. Hypothalamic NPY
mRNA and
peptide levels were measured using in situ hybridization and immunocytochemistry, respectively. BMOV treatment significantly reduced food intake, body fat,
body weight, plasma
insulin levels, and
glucose levels in fatty Zucker rats. Fifteen minutes after
insulin injection (5 U/kg, intravenous [IV]), circulating
leptin levels (+100%) and adipose
leptin levels (+60%) were elevated in BMOV-treated fatty rats, although these effects were not observed in untreated fatty rats. NPY
mRNA levels in the arcuate nucleus (
ARC) (-29%), NPY
peptide levels in
ARC (-31%), as well as in the paraventricular nucleus (PVN) (-37%) were decreased with BMOV treatment in these fatty rats. These data indicate that BMOV may increase
insulin sensitivity in adipose tissue and decrease appetite and body fat by decreasing NPY levels in the hypothalamus. BMOV-induced reduction in appetite and
weight gain along with normalized
insulin levels in models of
obesity, suggest its possible use as a therapeutic agent in
obesity.