Human Molecular Genetics, 2003, Vol. 12, No. 5 551-559
© 2003 Oxford University Press
The voltage-gated potassium channel Kv1.3 regulates energy homeostasis and body weight
1Department of Medicine, 2Section of Immunobiology, 3Department of Pharmacology, 4Howard Hughes Medical Institute and 5Yale University School of Medicine, New Haven, CT, USA, 6VA CT Medical Center, New Haven, CT, USA, 7Medical College of Georgia, Augusta, GA, USA and 8RIKEN Research Center for Allergy and Immunology, Yokohama, Japan
Received November 4, 2002; Revised December 23, 2002; Accepted January 3, 2003
Voltage-gated potassium (Kv) channels regulate cell membrane potential and control a variety of cellular processes. Kv1.3 channels are expressed in several tissues and believed to participate in cell volume regulation, apoptosis, T cell activation and renal solute homeostasis. Examination of Kv1.3-deficient mice (Kv1.3-/-), generated by gene targeting, revealed a previously unrecognized role for Kv1.3 in body weight regulation. Indeed, Kv1.3-/- mice weigh significantly less than control littermates. Moreover, knockout mice are protected from diet-induced obesity and gain significantly less weight than littermate controls when placed on a high-fat diet. While food intake did not differ significantly between Kv1.3-/- and controls, basal metabolic rate, measured at rest by indirect calorimetry, was significantly higher in knockout animals. These data indicate that Kv1.3 channels may participate in the pathways that regulate body weight and that channel inhibition increases basal metabolic rate.
* To whom correspondence should be addressed at: Section of Nephrology, Department of Medicine, Yale School of Medicine, 333 Cedar Street, LMP 2073, PO Box 208029, New Haven, CT 06520-8029, USA. Tel: +1 2035062500; Fax: +1 5084628950; Email: gary.desir{at}yale.edu
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
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