Oral vanadium enhances the catabolic effects of central leptin in young adult rats.
Recently, vanadium has been shown to enhance leptin signal transduction in vitro. We hypothesized that chronic oral administration of an organic vanadium complex would enhance both leptin signaling and physiological responsiveness in vivo. Three-month-old F344 x Brown Norway male rats were provided a solution containing escalating doses of vanadyl acetoacetonate (V), peaking at 60 mg/liter elemental vanadium in drinking water on the 11th d of V treatment. Although V treatment tended to suppress weight gain, absolute body weights did not significantly differ between groups after 62 d of treatment. At this point, a permanent cannula was placed into the left lateral ventricle of all animals. The cannula was connected to a sc minipump providing either 5 microg/d leptin or artificial cerebral spinal fluid (ACSF) control solution. This yielded four groups: C-ACSF, C-leptin, V-ACSF, and V-leptin. During the ensuing 26 d, weight gain was similar in C-ACSF and V-ACSF. As expected, leptin caused dramatic weight loss in C-leptin, but leptin-induced weight loss was 43% greater in V-leptin. V enhanced leptin-induced signal transducer and activator of transcription-3 phosphorylation in the hypothalamus, whereas V alone had no effect. V also augmented the leptin-induced increase in brown adipose tissue uncoupling protein-1. The effects of vanadium on responsiveness to a submaximal dose of leptin (0.25 microg/d) were also evaluated, yielding qualitatively similar results. These data demonstrate, for the first time, that chronic V administration enhances the weight-reducing effects of centrally administered leptin in young adult animals, and the mechanism appears to involve enhanced leptin signal transduction.
Wilsey
Jared
J
Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, Florida 32608-1197, USA.
Matheny
Michael K
MK
Scarpace
Philip J
PJ
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D005951:Glucose Tolerance Test; D007276:Injections, Intraventricular; D020738:Leptin / Q000008:administration & dosage* / Q000097:blood* / Q000235:genetics / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D014639:Vanadium / Q000008:administration & dosage / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
D001786:Blood Glucose; D020738:Leptin; D012333:RNA, Messenger; D014639:Vanadium