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

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

Author Benfato, Izabelle Dias Autor UNIFESP Google Scholar
Moretto, Thais Ludmilla Autor UNIFESP Google Scholar
de Carvalho, Francine Pereira Autor UNIFESP Google Scholar
Barthichoto, Marcela Autor UNIFESP Google Scholar
Ferreira, Sandra Mara Google Scholar
Costa Junior, Jose Maria Google Scholar
Lazzarin, Mariana Cruz Autor UNIFESP Google Scholar
de Oliveira, Flavia Autor UNIFESP Google Scholar
Martinez, Carolina Autor UNIFESP Google Scholar
Carvalho, Carolina Prado de França Autor UNIFESP Google Scholar
Oliveira, Camila Aparecida Machado de Autor UNIFESP Google Scholar
Abstract 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 10thmonth 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 8months of age. Energy expenditure decreased from the 8thmonth. Hypothalamic BDNF protein expression and insulin signalling did not change throughout the time span studied. Leptin signalling decreased at 6 and 10months compared with 4months. Also, compared with 4months, 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.
Keywords Sedentary behavior
Leptin
Insulin
BDNF
hypothalamus
Ageing
xmlui.dri2xhtml.METS-1.0.item-coverage Hoboken
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Grant number FAPESP: 2011/05932-3
FAPESP: 2013/01624-8
Date 2017
Published in Experimental Physiology. Hoboken, v. 102, n. 11, p. 1524-1534, 2017.
ISSN 0958-0670 (Sherpa/Romeo, impact factor)
Publisher Wiley
Extent 1524-1534
Origin http://dx.doi.org/10.1113/EP086265
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000414175100020
URI https://repositorio.unifesp.br/handle/11600/58291

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