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J Endocrinol Invest. 2015 Feb;38(2):125-31. doi: 10.1007/s40618-014-0225-z. Epub 2014 Dec 13.

Fuel homeostasis and locomotor behavior: role of leptin and melanocortin pathways.

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Obesity Center at the Endocrine Unit, University Hospital of Pisa, Pisa, Italy.
Obesity Center at the Endocrine Unit, University Hospital of Pisa, Pisa, Italy.
National Research Council, Institute of Clinical Physiology, Pisa, Italy.
Obesity Center at the Endocrine Unit, University Hospital of Pisa, Pisa, Italy.



While it is now accepted that genes and their products affect food intake, the concept that locomotor behavior or the propensity for physical activity is controlled by neuro hum oral regulators is frequently underappreciated. In mammals, complex interactions have developed to allow the cross-talk between fuel homeostasis and physical activity.


The aim of this review is to provide a synopsis of the influence of the leptin-melanocortin pathway, a well-studied pivotal player in body weight regulation, on locomotor behaviors.


In rodents, reductions in leptin levels that physiologically occur following acute food deprivation or a reduction of the fat mass consequent to prolonged caloric restrictions are associated with a decrease in total locomotor activity and simultaneous increase in food-anticipatory activity, a locomotor behavior which reflects a foraging attitude. These actions can be prevented by leptin administration and are at least partially mediated by the neurons of the melanocortin pathway. In humans, twin studies have attributed to genetic factors approximately 50% of the variance of physical activity. An elevated number of the genes or loci which may affect physical activity are involved in body weight homeostasis. Polymorphisms of the melanocortin-4 and leptin receptors have repeatedly been associated with the level of physical activity. Unraveling the complexity of the regulation of locomotor behavior and the interconnections with the pathways involved in energy homeostasis may help explain the substantial individual variability in physical activities in humans and disentangle the harmful effects of sedentary lifestyle, which may be distinct from the detrimental effects of obesity.


Anorexia nervosa; Food anticipatory activity; Leptin; Locomotor activity; Melanocortin system; Obesity; Physical activity

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