PMID- 28786537
OWN - NLM
STAT- MEDLINE
DCOM- 20180709
LR  - 20181202
IS  - 1469-445X (Electronic)
IS  - 0958-0670 (Linking)
VI  - 102
IP  - 11
DP  - 2017 Nov 1
TI  - Spontaneous physical activity and mediators of energy homeostasis in the 
      hypothalamus of mice from 4 to 10 months of age.
PG  - 1524-1534
LID - 10.1113/EP086265 [doi]
AB  - 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.
CI  - (c) 2017 The Authors. Experimental Physiology (c) 2017 The Physiological Society.
FAU - Benfato, Izabelle Dias
AU  - Benfato ID
AD  - Department of Biosciences, Institute of Health and Society, Federal University of 
      Sao Paulo, Santos, SP, Brazil.
FAU - Moretto, Thais Ludmilla
AU  - Moretto TL
AD  - Department of Biosciences, Institute of Health and Society, Federal University of 
      Sao Paulo, Santos, SP, Brazil.
FAU - de Carvalho, Francine Pereira
AU  - de Carvalho FP
AD  - Department of Biosciences, Institute of Health and Society, Federal University of 
      Sao Paulo, Santos, SP, Brazil.
FAU - Barthichoto, Marcela
AU  - Barthichoto M
AD  - Department of Biosciences, Institute of Health and Society, Federal University of 
      Sao Paulo, Santos, SP, Brazil.
FAU - Ferreira, Sandra Mara
AU  - Ferreira SM
AD  - Department of Structural and Functional Biology, Biology Institute, State 
      University of Campinas (Unicamp), Campinas, SP, Brazil.
FAU - Costa Junior, Jose Maria
AU  - Costa Junior JM
AD  - Department of Structural and Functional Biology, Biology Institute, State 
      University of Campinas (Unicamp), Campinas, SP, Brazil.
FAU - Lazzarin, Mariana Cruz
AU  - Lazzarin MC
AD  - Department of Biosciences, Institute of Health and Society, Federal University of 
      Sao Paulo, Santos, SP, Brazil.
FAU - de Oliveira, Flavia
AU  - de Oliveira F
AD  - Department of Biosciences, Institute of Health and Society, Federal University of 
      Sao Paulo, Santos, SP, Brazil.
FAU - Martinez, Carolina
AU  - Martinez C
AD  - Department of Biosciences, Institute of Health and Society, Federal University of 
      Sao Paulo, Santos, SP, Brazil.
FAU - Prado de Franca Carvalho, Carolina
AU  - Prado de Franca Carvalho C
AD  - Department of Biosciences, Institute of Health and Society, Federal University of 
      Sao Paulo, Santos, SP, Brazil.
FAU - de Oliveira, Camila Aparecida Machado
AU  - de Oliveira CAM
AD  - Department of Biosciences, Institute of Health and Society, Federal University of 
      Sao Paulo, Santos, SP, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20170920
PL  - England
TA  - Exp Physiol
JT  - Experimental physiology
JID - 9002940
RN  - 0 (Blood Glucose)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Insulin)
RN  - 0 (Leptin)
SB  - IM
MH  - Adiposity
MH  - Age Factors
MH  - Aging/*metabolism
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - *Energy Metabolism
MH  - Glucose Intolerance/metabolism
MH  - Homeostasis
MH  - Hypothalamus/*metabolism
MH  - Insulin/metabolism
MH  - Insulin Resistance
MH  - Leptin/metabolism
MH  - Locomotion
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Muscle, Skeletal/metabolism
MH  - *Physical Exertion
MH  - Sedentary Behavior
MH  - Signal Transduction
OTO - NOTNLM
OT  - Ageing
OT  - BDNF
OT  - Insulin
OT  - Leptin
OT  - Sedentary behavior
OT  - hypothalamus
EDAT- 2017/08/09 06:00
MHDA- 2018/07/10 06:00
CRDT- 2017/08/09 06:00
PHST- 2017/01/12 00:00 [received]
PHST- 2017/08/04 00:00 [accepted]
PHST- 2017/08/09 06:00 [pubmed]
PHST- 2018/07/10 06:00 [medline]
PHST- 2017/08/09 06:00 [entrez]
AID - 10.1113/EP086265 [doi]
PST - ppublish
SO  - Exp Physiol. 2017 Nov 1;102(11):1524-1534. doi: 10.1113/EP086265. Epub 2017 Sep 
      20.