Diet-Induced Obesity Resistance of Kv1.3−/− Mice is Olfactory Bulb Dependent

• Published in: Journal of neuroendocrinology 2012-08, Vol.24 (8), p.1087-1095
• Main Authors: Tucker, K., Overton, J. M., Fadool, D. A.
• Format: Article
• Language: English
• Subjects: Age; Animals; Behavior, Animal; Biological and medical sciences; Calorimetry, Indirect; Diet; diet-induced obesity; Energy balance; Energy expenditure; Energy Intake; Energy metabolism; Fasting; Fundamental and applied biological sciences. Psychology; Gene Targeting; Glucose; High fat diet; Kv1.3 Potassium Channel - genetics; Kv1.3 Potassium Channel - physiology; Leptin; Light effects; Locomotor activity; Medical sciences; Metabolic diseases; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Obesity - genetics; Obesity - physiopathology; Obesity - prevention & control; Olfactory bulb; Olfactory Bulb - physiopathology; Olfactory Bulb - surgery; olfactory bulbectomy; Olfactory system; Olfactory system and olfaction. Gustatory system and gustation; Olfactory thresholds; Oxygen consumption; potassium channel; Potassium channels (voltage-gated); super-smeller; Surgery; Vertebrates: endocrinology; Vertebrates: nervous system and sense organs; Water intake
• ISSN: 0953-8194; 1365-2826
• DOI: 10.1111/j.1365-2826.2012.02314.x

Gene‐targeted deletion of the voltage‐gated potassium channel, Kv1.3 (Kv1.3−/−), increases olfactory sensitivity and discriminatory ability, and causes resistance to diet‐induced obesity (DIO) in mice. The present study aimed to determine whether the enhanced olfactory ability of the Kv1.3−/− mouse contributes to the resistance to DIO. Kv1.3+/+ and Kv1.3−/− mice were subject to bilateral olfactory bulbectomy (OBX) or sham surgery at 9 weeks of age and placed on either a control chow diet or a 32% moderately high‐fat diet (MHF). Caloric and water intake, locomotor activity and oxygen consumption were monitored after 5 weeks of diet treatment. At the end of 26 weeks of diet treatment, fat pad weight and blood chemistry were evaluated. Kv1.3+/+ mice exhibited a significant increase in weight, adiposity, fasting glucose and fasting leptin in response to the MHF‐diet, with or without OBX. When treated with a MHF‐diet, Kv1.3−/− mice gained significantly less weight than Kv1.3+/+ mice and exhibited a significant increase in light phase metabolism. OBX of Kv1.3−/− mice prevented the resistance to DIO and concomitant up‐regulation of light phase metabolism at the same time as decreasing dark phase metabolism and total energy expenditure. These findings suggest that pathways activated in Kv1.3−/− that increased energy expenditure and led to resistance to DIO are olfactory bulb dependent. Thus, these findings add to a growing body of evidence suggesting that the olfactory system can modulate the pathways involved in the regulation of energy balance.