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

Autor: Benfato ID; Department of Biosciences, Institute of Health and Society, Federal University of Sao Paulo, Santos, SP, Brazil., Moretto TL; Department of Biosciences, Institute of Health and Society, Federal University of Sao Paulo, Santos, SP, Brazil., de Carvalho FP; Department of Biosciences, Institute of Health and Society, Federal University of Sao Paulo, Santos, SP, Brazil., Barthichoto M; Department of Biosciences, Institute of Health and Society, Federal University of Sao Paulo, Santos, SP, Brazil., Ferreira SM; Department of Structural and Functional Biology, Biology Institute, State University of Campinas (Unicamp), Campinas, SP, Brazil., Costa Júnior JM; Department of Structural and Functional Biology, Biology Institute, State University of Campinas (Unicamp), Campinas, SP, Brazil., Lazzarin MC; Department of Biosciences, Institute of Health and Society, Federal University of Sao Paulo, Santos, SP, Brazil., de Oliveira F; Department of Biosciences, Institute of Health and Society, Federal University of Sao Paulo, Santos, SP, Brazil., Martinez C; Department of Biosciences, Institute of Health and Society, Federal University of Sao Paulo, Santos, SP, Brazil., Prado de França Carvalho C; Department of Biosciences, Institute of Health and Society, Federal University of Sao Paulo, Santos, SP, Brazil., de Oliveira CAM; Department of Biosciences, Institute of Health and Society, Federal University of Sao Paulo, Santos, SP, Brazil.
Jazyk: angličtina
Zdroj: Experimental physiology [Exp Physiol] 2017 Nov 01; Vol. 102 (11), pp. 1524-1534. Date of Electronic Publication: 2017 Sep 20.
DOI: 10.1113/EP086265
Abstrakt: New Findings: What is the central question of this study? Is the initial decline of spontaneous physical activity (SPA) in mice related to impaired insulin and leptin signalling or brain-derived neurotrophic factor expression in the hypothalamus? What is the main finding and its importance? We showed that SPA started to decline at an early stage, concomitantly with an impairment of hypothalamic leptin signalling. Consequently, energy expenditure decreased and glucose tolerance worsened. Our results demonstrate the need to counteract the initial decline in SPA to avoid metabolic impairments and indicate the possible involvement of central leptin in the reduction in SPA with age. The biological control of physical activity is poorly understood. Age decreases insulin, leptin and brain-derived neurotrophic factor (BDNF) signalling 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. Spontaneous physical activity (and other parameters of locomotion) and energy expenditure were determined monthly in mice from the 4th to the 10th month of age. Metabolic and hypothalamic analyses were performed in 4-, 6- and 10-month-old mice. Spontaneous physical activity, 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. Energy expenditure decreased from the 8th month. Hypothalamic BDNF protein expression and insulin signalling did not change throughout the time span studied. Leptin signalling decreased at 6 and 10 months compared with 4 months. Also, compared with 4 months, 6- and 10-month-old mice were glucose intolerant. In conclusion, SPA begins to decline in parallel with reduced hypothalamic leptin signalling. Metabolic impairment also manifests as SPA decreases, highlighting the need to understand the regulation of SPA in order to combat its decline.
(© 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.)
Databáze: MEDLINE
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