Identification of a physiological role for leptin in the regulation of ambulatory activity and wheel running in mice

• Published in: American journal of physiology: endocrinology and metabolism Vol. 300; no. 2; pp. E392 - E401
• Main Authors: Morton, Gregory J., Kaiyala, Karl J., Fisher, Jonathan D., Ogimoto, Kayoko, Schwartz, Michael W., Wisse, Brent E.
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.02.2011
• Subjects: Animal subjects; Animals; Blood; Body Composition; Calorimetry, Indirect; Darkness; Dose-Response Relationship, Drug; Energy cost; Energy Metabolism; Enzyme-Linked Immunosorbent Assay; Exercise; Fasting - physiology; Food availability; Genetics; Hormones; Hypothalamus - metabolism; Leptin - metabolism; Leptin - pharmacology; Leptin - physiology; Light; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Motor Activity - drug effects; Motor Activity - physiology; Neuropeptides - biosynthesis; Neuropeptides - genetics; Oxygen Consumption - physiology; Physiology; Plasma; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Running (effects); Running - physiology
• ISSN: 0193-1849; 1522-1555; 1522-1555
• DOI: 10.1152/ajpendo.00546.2010

Mechanisms regulating spontaneous physical activity remain poorly characterized despite evidence of influential genetic and acquired factors. We evaluated ambulatory activity and wheel running in leptin-deficient ob/ob mice and in wild-type mice rendered hypoleptinemic by fasting in both the presence and absence of subcutaneous leptin administration. In ob/ob mice, leptin treatment to plasma levels characteristic of wild-type mice acutely increased both ambulatory activity (by 4,000 ± 200 beam breaks/dark cycle, P < 0.05) and total energy expenditure (TEE; by 0.11 ± 0.01 kcal/h during the dark cycle, P < 0.05) in a dose-dependent manner and acutely increased wheel running (+350%, P < 0.05). Fasting potently increased ambulatory activity and wheel running in wild-type mice (AA: +25%, P < 0.05; wheel running: +80%, P < 0.05), and the effect of fasting was more pronounced in ob/ob mice (AA: +400%, P < 0.05; wheel running: +1,600%, P < 0.05). However, unlike what occurred in ad libitum-fed ob/ob mice, physiological leptin replacement attenuated or prevented fasting-induced increases of ambulatory activity and wheel running in both wild-type and ob/ob mice. Thus, plasma leptin is a physiological regulator of spontaneous physical activity, but the nature of leptin's effect on activity is dependent on food availability.