PMID- 30076527
OWN - NLM
STAT- MEDLINE
DCOM- 20190806
LR  - 20201119
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Print)
IS  - 0893-7648 (Linking)
VI  - 56
IP  - 4
DP  - 2019 Apr
TI  - Modulation of Glucose Metabolism in Hippocampal Neurons by Adiponectin and 
      Resistin.
PG  - 3024-3037
LID - 10.1007/s12035-018-1271-x [doi]
AB  - Obese individuals exhibit altered circulating levels of adipokines, the proteins 
      secreted by adipose tissue to mediate tissue cross-talk and regulate appetite and 
      energy expenditure. The effect of adipokines on neuronal glucose metabolism, 
      however, remains largely unknown. Two adipokines produced in adipose tissue, 
      adiponectin and resistin, can gain access to the central nervous system (CNS), 
      and their levels in the cerebrospinal fluid (CSF) are altered in obesity. We 
      hypothesized that dysregulated adipokines in the CNS may underlie the reported 
      link between obesity and higher risk of neurological disorders like Alzheimer's 
      disease (AD), by affecting glucose metabolism in hippocampal neurons. Using 
      cultured primary rat hippocampal neurons and mouse hippocampus slices, we show 
      that recombinant adiponectin and resistin, at a concentration found in the CSF, 
      have opposing effects on glucose metabolism. Adiponectin enhanced glucose uptake, 
      glycolytic rate, and ATP production through an AMP-activated protein kinase 
      (AMPK)-dependent mechanism; inhibiting AMPK abrogated the effects of adiponectin 
      on glucose uptake and utilization. In contrast, resistin reduced glucose uptake, 
      glycolytic rate, and ATP production, in part, by inhibiting hexokinase (HK) 
      activity in hippocampal neurons. These data suggest that altered CNS levels of 
      adipokines in the context of obesity may impact glucose metabolism in hippocampal 
      neurons, brain region involved in learning and memory functions.
FAU - Cisternas, Pedro
AU  - Cisternas P
AD  - Centro de Envejecimiento y Regeneracion (CARE-UC), Departamento de Biologia 
      Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad 
      Catolica de Chile, Alameda Bernardo O'Higgins 340, P. O. Box 114-D, Santiago, 
      Chile. pcisternas@bio.puc.cl.
FAU - Martinez, Milka
AU  - Martinez M
AD  - Centro de Envejecimiento y Regeneracion (CARE-UC), Departamento de Biologia 
      Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad 
      Catolica de Chile, Alameda Bernardo O'Higgins 340, P. O. Box 114-D, Santiago, 
      Chile.
FAU - Ahima, Rexford S
AU  - Ahima RS
AD  - Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns 
      Hopkins University School of Medicine, Baltimore, MD, USA.
FAU - William Wong, G
AU  - William Wong G
AD  - Department of Physiology and Center for Metabolism and Obesity Research, Johns 
      Hopkins University School of Medicine, Baltimore, MD, USA.
FAU - Inestrosa, Nibaldo C
AU  - Inestrosa NC
AUID- ORCID: 0000-0003-3118-9726
AD  - Centro de Envejecimiento y Regeneracion (CARE-UC), Departamento de Biologia 
      Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad 
      Catolica de Chile, Alameda Bernardo O'Higgins 340, P. O. Box 114-D, Santiago, 
      Chile. ninestrosa@bio.puc.cl.
AD  - Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, 
      University of New South Wales, Sydney, Australia. ninestrosa@bio.puc.cl.
AD  - Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de 
      Magallanes, Punta Arenas, Chile. ninestrosa@bio.puc.cl.
LA  - eng
GR  - R01 DK084171/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20180803
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Adiponectin)
RN  - 0 (Resistin)
RN  - IY9XDZ35W2 (Glucose)
MH  - Adiponectin/*pharmacology
MH  - Animals
MH  - Cells, Cultured
MH  - Glucose/*metabolism
MH  - Glycolysis/drug effects
MH  - Hippocampus/*cytology/*metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Models, Biological
MH  - Neurons/drug effects/*metabolism
MH  - Rats, Sprague-Dawley
MH  - Resistin/*pharmacology
PMC - PMC7672532
MID - NIHMS1645631
OTO - NOTNLM
OT  - Adiponectin
OT  - Brain functions
OT  - Glucose metabolism
OT  - Hippocampus
OT  - Obesity
OT  - Resistin
COIS- Conflict of Interest The authors declare that they have no conflicts of interest.
EDAT- 2018/08/05 06:00
MHDA- 2019/08/07 06:00
PMCR- 2020/11/18
CRDT- 2018/08/05 06:00
PHST- 2018/05/24 00:00 [received]
PHST- 2018/07/19 00:00 [accepted]
PHST- 2018/08/05 06:00 [pubmed]
PHST- 2019/08/07 06:00 [medline]
PHST- 2018/08/05 06:00 [entrez]
PHST- 2020/11/18 00:00 [pmc-release]
AID - 10.1007/s12035-018-1271-x [pii]
AID - 10.1007/s12035-018-1271-x [doi]
PST - ppublish
SO  - Mol Neurobiol. 2019 Apr;56(4):3024-3037. doi: 10.1007/s12035-018-1271-x. Epub 
      2018 Aug 3.