PMID- 29935237
OWN - NLM
STAT- MEDLINE
DCOM- 20190325
LR  - 20220301
IS  - 1532-8600 (Electronic)
IS  - 0026-0495 (Linking)
VI  - 87
DP  - 2018 Oct
TI  - BDNF mimetic alleviates body weight gain in obese mice by enhancing mitochondrial 
      biogenesis in skeletal muscle.
PG  - 113-122
LID - S0026-0495(18)30141-0 [pii]
LID - 10.1016/j.metabol.2018.06.007 [doi]
AB  - BACKGROUND: 7,8-Dihydroxyflavone (7,8-DHF) is a small molecular weight compound 
      that mimics the functions of brain-derived neurotrophic factor (BDNF). The 
      current study aims to elucidate the molecular mechanism of 7,8-DHF-induced body 
      weight regulation. METHODS: Obese female C57/BL6 (20-week-old) mice that have 
      been fed with high-fat diet for 13 weeks were treated with 7,8-DHF for 9 weeks. 
      Various biochemical and molecular analyses were performed to examine the signal 
      transduction pathway, metabolite content, and mitochondrial mass in the animals. 
      Moreover, systemic energy metabolism and insulin sensitivity were determined by 
      indirect calorimetry and insulin/glucose-tolerance tests. We have also determined 
      the metabolic actions of 7,8-DHF on cultured myotubes. RESULTS: 7,8-DHF treatment 
      increased cellular respiration by promoting mitochondrial biogenesis in cultured 
      skeletal muscle cells. In diet-induced obese mice, subsequent 7,8-DHF consumption 
      triggered the AMPK/CREB/PGC-1alpha pathways to increase the muscular mitochondrial 
      content. Systemic energy metabolism was thus elevated, which reduced the body 
      weight gain in obese animals. Consequently, hyperlipidemia, hyperglycemia 
      hyperinsulinemia, and ectopic lipid accumulation in skeletal muscle and liver of 
      the obese animals were alleviated after 7,8-DHF treatment. Moreover, insulin 
      sensitivity of the obese muscle was improved after 7,8-DHF consumption. 
      CONCLUSION: 7,8-DHF treatment increases muscular mitochondrial respiration and 
      systemic energy expenditure, which alleviates the body weight gain and partially 
      reverse the metabolic abnormalities induced by obesity.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Wood, John
AU  - Wood J
AD  - Department of Physiology, the University of Oklahoma Health Sciences Center, 
      Oklahoma City, USA.
FAU - Tse, Margaret Chui Ling
AU  - Tse MCL
AD  - School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of 
      Hong Kong, China.
FAU - Yang, Xiuying
AU  - Yang X
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Beijing Key Laboratory of Drug Target and Screening Research, Institute of 
      Materia Medica of Peking Union Medical College, Beijing, China.
FAU - Brobst, Daniel
AU  - Brobst D
AD  - Department of Physiology, the University of Oklahoma Health Sciences Center, 
      Oklahoma City, USA.
FAU - Liu, Zhixue
AU  - Liu Z
AD  - Department of Physiology, the University of Oklahoma Health Sciences Center, 
      Oklahoma City, USA.
FAU - Pang, Brian Pak Shing
AU  - Pang BPS
AD  - School of Biological Sciences, the University of Hong Kong, Hong Kong, SAR, 
      China.
FAU - Chan, Wing Suen
AU  - Chan WS
AD  - School of Biological Sciences, the University of Hong Kong, Hong Kong, SAR, 
      China.
FAU - Zaw, Aung Moe
AU  - Zaw AM
AD  - School of Biological Sciences, the University of Hong Kong, Hong Kong, SAR, 
      China.
FAU - Chow, Billy K C
AU  - Chow BKC
AD  - School of Biological Sciences, the University of Hong Kong, Hong Kong, SAR, 
      China.
FAU - Ye, Keqiang
AU  - Ye K
AD  - Department of Pathology, Emory University School of Medicine, Atlanta, USA.
FAU - Lee, Chi Wai
AU  - Lee CW
AD  - School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of 
      Hong Kong, China.
FAU - Chan, Chi Bun
AU  - Chan CB
AD  - School of Biological Sciences, the University of Hong Kong, Hong Kong, SAR, 
      China; State Key Laboratory of Pharmaceutical Biotechnology, The University of 
      Hong Kong, Hong Kong, SAR, China. Electronic address: chancb@hku.hk.
LA  - eng
GR  - U2C DK093000/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180620
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (6,7-dihydroxyflavone)
RN  - 0 (Anti-Obesity Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Flavones)
SB  - IM
MH  - Adipocytes/drug effects/ultrastructure
MH  - Animals
MH  - Anti-Obesity Agents/*pharmacology
MH  - *Biomimetics
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Diet, High-Fat
MH  - Energy Metabolism/drug effects
MH  - Female
MH  - Flavones/*pharmacology
MH  - Glucose Tolerance Test
MH  - Insulin Resistance
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Obese
MH  - Mitochondria, Muscle/*drug effects
MH  - Muscle, Skeletal/*drug effects
MH  - Obesity/*drug therapy
MH  - Organelle Biogenesis
MH  - Signal Transduction/drug effects
MH  - Weight Gain/*drug effects
OTO - NOTNLM
OT  - 7,8-Dihydroxyflavone
OT  - Mitochondrial
OT  - Obesity
OT  - Skeletal muscle
EDAT- 2018/06/24 06:00
MHDA- 2019/03/26 06:00
CRDT- 2018/06/24 06:00
PHST- 2018/01/29 00:00 [received]
PHST- 2018/05/14 00:00 [revised]
PHST- 2018/06/17 00:00 [accepted]
PHST- 2018/06/24 06:00 [pubmed]
PHST- 2019/03/26 06:00 [medline]
PHST- 2018/06/24 06:00 [entrez]
AID - S0026-0495(18)30141-0 [pii]
AID - 10.1016/j.metabol.2018.06.007 [doi]
PST - ppublish
SO  - Metabolism. 2018 Oct;87:113-122. doi: 10.1016/j.metabol.2018.06.007. Epub 2018 
      Jun 20.