PMID- 34063911
OWN - NLM
STAT- MEDLINE
DCOM- 20210622
LR  - 20240402
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 11
DP  - 2021 May 21
TI  - Deficient Leptin Cellular Signaling Plays a Key Role in Brain Ultrastructural 
      Remodeling in Obesity and Type 2 Diabetes Mellitus.
LID - 10.3390/ijms22115427 [doi]
LID - 5427
AB  - The triad of obesity, metabolic syndrome (MetS), Type 2 diabetes mellitus (T2DM) 
      and advancing age are currently global societal problems that are expected to 
      grow over the coming decades. This triad is associated with multiple end-organ 
      complications of diabetic vasculopathy (maco-microvessel disease), neuropathy, 
      retinopathy, nephropathy, cardiomyopathy, cognopathy encephalopathy and/or 
      late-onset Alzheimer's disease. Further, obesity, MetS, T2DM and their 
      complications are associated with economical and individual family burdens. This 
      review with original data focuses on the white adipose tissue-derived 
      adipokine/hormone leptin and how its deficient signaling is associated with brain 
      remodeling in hyperphagic, obese, or hyperglycemic female mice. Specifically, the 
      ultrastructural remodeling of the capillary neurovascular unit, brain endothelial 
      cells (BECs) and their endothelial glycocalyx (ecGCx), the blood-brain barrier 
      (BBB), the ventricular ependymal cells, choroid plexus, blood-cerebrospinal fluid 
      barrier (BCSFB), and tanycytes are examined in female mice with impaired leptin 
      signaling from either dysfunction of the leptin receptor (DIO and db/db models) 
      or the novel leptin deficiency (BTBR ob/ob model).
FAU - Hayden, Melvin R
AU  - Hayden MR
AUID- ORCID: 0000-0001-5178-4245
AD  - Departments of Internal Medicine, Endocrinology Diabetes and Metabolism, Diabetes 
      and Cardiovascular Disease Center, University of Missouri-Columbia School of 
      Medicine, One Hospital Drive, Columbia, MO 65212, USA.
FAU - Banks, William A
AU  - Banks WA
AD  - Geriatrics Research, Education and Clinical Center, Veterans Affairs Puget Sound 
      Health Care System, 1660 S. Columbian Way, 810C/Bldg 1, Seattle, WA 98108, USA.
AD  - Department of Medicine, Division of Gerontology and Geriatric Medicine, 
      University of Washington, Seattle, WA 98108, USA.
LA  - eng
GR  - 1R01AG059088/NH/NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20210521
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Leptin)
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier/metabolism
MH  - Brain/*metabolism
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Disease Models, Animal
MH  - Humans
MH  - Leptin/*metabolism
MH  - Mice, Obese/metabolism
MH  - Obesity/*metabolism
MH  - Signal Transduction/*physiology
MH  - Mice
PMC - PMC8196569
OTO - NOTNLM
OT  - adipose tissue
OT  - aging
OT  - blood-brain barrier
OT  - blood-cerebrospinal fluid barrier
OT  - endothelial cell
OT  - endothelial glycocalyx
OT  - insulin resistance
OT  - leptin resistance
OT  - microglia
OT  - neurovascular unit
OT  - obesity
OT  - permeability
OT  - ultrastructure
COIS- The authors declare no conflict of interest.
EDAT- 2021/06/03 06:00
MHDA- 2021/06/23 06:00
PMCR- 2021/05/21
CRDT- 2021/06/02 01:08
PHST- 2021/04/14 00:00 [received]
PHST- 2021/05/13 00:00 [revised]
PHST- 2021/05/15 00:00 [accepted]
PHST- 2021/06/02 01:08 [entrez]
PHST- 2021/06/03 06:00 [pubmed]
PHST- 2021/06/23 06:00 [medline]
PHST- 2021/05/21 00:00 [pmc-release]
AID - ijms22115427 [pii]
AID - ijms-22-05427 [pii]
AID - 10.3390/ijms22115427 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 May 21;22(11):5427. doi: 10.3390/ijms22115427.