Effect of vanadium on insulin sensitivity and appetite.
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.
Wang
J
J
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
Yuen
V G
VG
McNeill
J H
JH
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001066:Appetite / Q000187:drug effects*; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D002467:Cell Nucleus / Q000378:metabolism; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D020738:Leptin / Q000032:analysis / Q000097:blood; D008297:Male; D009478:Neuropeptide Y / Q000032:analysis / Q000097:blood; D009765:Obesity / Q000097:blood / Q000378:metabolism; D011753:Pyrones / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011924:Rats, Zucker; D014638:Vanadates / Q000494:pharmacology; D014639:Vanadium / Q000494:pharmacology*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D009478:Neuropeptide Y; D011753:Pyrones; D012333:RNA, Messenger; D014639:Vanadium; C074212:bis(maltolato)oxovanadium(IV); D014638:Vanadates