PMID- 29914985
OWN - NLM
STAT- MEDLINE
DCOM- 20190228
LR  - 20210205
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 293
IP  - 34
DP  - 2018 Aug 24
TI  - Inhibition of the CD36 receptor reduces visceral fat accumulation and improves 
      insulin resistance in obese mice carrying the BDNF-Val66Met variant.
PG  - 13338-13348
LID - 10.1074/jbc.RA118.002405 [doi]
AB  - Obesity-induced metabolic dysfunctions increase the risk for vascular diseases, 
      including type II diabetes and stroke. Managing obesity is of interest to address 
      the worldwide health problem; however, the role of genetic variability in human 
      obesity development and specific targets for obesity-related metabolic disease 
      have not been thoroughly studied. A SNP in the brain-derived neurotropic factor 
      (BDNF) gene that results in the substitution of a valine with a methionine at 
      codon 66 (Val66Met) occurs with a high frequency in humans. This study addressed 
      the effect of genetic variability in developing obesity and the efficacy of the 
      inhibition of cluster of differentiation 36 (CD36), a multifunctional receptor 
      implicated in obesity and insulin resistance, in WT mice and mice with the BDNF 
      Val66Met variant. CD36 inhibition by salvionolic acid B (SAB) in diet-induced 
      obese WT mice reduced visceral fat accumulation and improved insulin resistance. 
      The benefit of SAB was abrogated in CD36 knockout mice, showing the specificity 
      of SAB. In addition, mice with the Val66Met variant in both alleles (BDNF(M/M)) 
      fed a high-fat diet exhibited extreme obesity with increased CD36 gene and 
      protein levels in macrophages. Chronic SAB treatment in BDNF(M/M) mice 
      significantly decreased visceral fat accumulation and improved insulin 
      resistance. Notably, the effect of SAB was greater in the extremely obese 
      BDNF(M/M) mice compared with the WT mice. The study demonstrated a link between 
      BDNF Val66Met and elevated CD36 expression and suggested that CD36 inhibition may 
      be a potential strategy to improve metabolic dysfunctions and to normalize risk 
      factors for vascular diseases in the obese population.
CI  - (c) 2018 Yang et al.
FAU - Yang, Jiwon
AU  - Yang J
AD  - From the Burke Medical Research Institute, White Plains, New York 10605 and.
FAU - Park, Keun Woo
AU  - Park KW
AD  - From the Burke Medical Research Institute, White Plains, New York 10605 and.
FAU - Cho, Sunghee
AU  - Cho S
AD  - From the Burke Medical Research Institute, White Plains, New York 10605 and 
      suc2002@med.cornell.edu.
AD  - the Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New 
      York, New York 10065.
LA  - eng
GR  - R01 HL082511/HL/NHLBI NIH HHS/United States
GR  - R01 NS077897/NS/NINDS NIH HHS/United States
GR  - R01 NS095359/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180618
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Bdnf protein, mouse)
RN  - 0 (Benzofurans)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (CD36 Antigens)
RN  - AE28F7PNPL (Methionine)
RN  - C1GQ844199 (salvianolic acid B)
RN  - HG18B9YRS7 (Valine)
SB  - IM
CIN - J Biol Chem. 2018 Aug 24;293(34):13349-13350. PMID: 30143599
MH  - Animals
MH  - Benzofurans/*pharmacology
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - CD36 Antigens/*antagonists & inhibitors/physiology
MH  - Cell Differentiation
MH  - Diet, High-Fat/adverse effects
MH  - *Insulin Resistance
MH  - *Intra-Abdominal Fat
MH  - Male
MH  - Methionine/chemistry/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Obese
MH  - *Mutation
MH  - Obesity/etiology/metabolism/pathology/*prevention & control
MH  - Valine/chemistry/genetics/metabolism
PMC - PMC6109932
OTO - NOTNLM
OT  - CD36
OT  - Type 2 diabetes
OT  - brain-derived neurotrophic factor (BDNF)
OT  - diabetes
OT  - insulin resistance
OT  - obesity
OT  - salvianolic acid B
COIS- Patent applications have been filed by Cornell Research Foundation, Inc. (CRF) 
      for the technology (CD36 inhibition to control visceral obesity/insulin 
      resistance) described in this article
EDAT- 2018/06/20 06:00
MHDA- 2019/03/01 06:00
PMCR- 2018/06/18
CRDT- 2018/06/20 06:00
PHST- 2018/02/12 00:00 [received]
PHST- 2018/06/12 00:00 [revised]
PHST- 2018/06/20 06:00 [pubmed]
PHST- 2019/03/01 06:00 [medline]
PHST- 2018/06/20 06:00 [entrez]
PHST- 2018/06/18 00:00 [pmc-release]
AID - S0021-9258(20)31039-5 [pii]
AID - RA118.002405 [pii]
AID - 10.1074/jbc.RA118.002405 [doi]
PST - ppublish
SO  - J Biol Chem. 2018 Aug 24;293(34):13338-13348. doi: 10.1074/jbc.RA118.002405. Epub 
      2018 Jun 18.