Spontaneous physical activity and mediators of energy homeostasis in the hypothalamus of mice from 4 to 10 months of age

Abstract

The biological control of physical activity is poorly understood. Age decreases insulin, leptin and brain-derived neurotrophic factor (BDNF) signaling in the hypothalamus and all have been shown to modulate spontaneous physical activity (SPA). We investigated the age at which SPA starts to decline and whether this is associated with the emergence of hypothalamic insulin and leptin resistance and reduced BDNF expression. SPA (and other parameters of locomotion) and energy expenditure (EE) were determined monthly in mice from the 4^th to the 10^th month of age. Metabolic and hypothalamic analyses were performed in 4 (4 m), 6 (6 m) and 10-month-old mice (10 m). SPA, distance travelled and speed of locomotion started to decrease in 6-month-old mice. The reduction in SPA became more evident from 8 months of age. EE decreased from the 8^th month. Hypothalamic BDNF protein expression and insulin signaling did not change in the time span studied. Leptin signaling decreased in 6 m and 10 m in relation to 4 m. Compared to 4 m, 6 m and 10 m mice were glucose intolerant. In conclusion, SPA begins to fall in parallel with reduced hypothalamic leptin signaling. Metabolic impairment also manifests as SPA decreases, highlighting the need to understand the regulation of SPA to combat its decline.

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