BDNF mimetic alleviates body weight gain in obese mice by enhancing mitochondrial biogenesis in skeletal muscle

John Wood, Margaret Chui Ling Tse, Xiuying Yang, Daniel Brobst, Zhixue Liu, Brian Pak Shing Pang, Wing Suen Chan, Aung Moe Zaw, Billy K.C. Chow, Keqiang Ye, Chi Wai Lee, Chi Bun Chan*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

44 Citations (Scopus)

Abstract

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-1α 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.

Original languageEnglish
Pages (from-to)113-122
Number of pages10
JournalMetabolism: Clinical and Experimental
Volume87
Early online date20 Jun 2018
DOIs
Publication statusPublished - Oct 2018

User-Defined Keywords

  • 7,8-Dihydroxyflavone
  • Obesity
  • Mitochondrial
  • Skeletal muscle

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