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

TitleBDNF mimetic alleviates body weight gain in obese mice by enhancing mitochondrial biogenesis in skeletal muscle
Authors
Keywords7,8-Dihydroxyflavone
Mitochondrial
Obesity
Skeletal muscle
Issue Date2018
PublisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/metabol
Citation
Metabolism, 2018, v. 87, p. 113-122 How to Cite?
AbstractBackground: 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. © 2018 Elsevier Inc.
Persistent Identifierhttp://hdl.handle.net/10722/256199
ISSN
2017 Impact Factor: 5.963
2015 SCImago Journal Rankings: 1.978
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWood, J-
dc.contributor.authorTse, CL-
dc.contributor.authorYang, X-
dc.contributor.authorBrobst, D-
dc.contributor.authorLiu, Z-
dc.contributor.authorZaw, AM-
dc.contributor.authorChow, BKC-
dc.contributor.authorLee, CW-
dc.contributor.authorChan, CB-
dc.date.accessioned2018-07-20T06:30:53Z-
dc.date.available2018-07-20T06:30:53Z-
dc.date.issued2018-
dc.identifier.citationMetabolism, 2018, v. 87, p. 113-122-
dc.identifier.issn0026-0495-
dc.identifier.urihttp://hdl.handle.net/10722/256199-
dc.description.abstractBackground: 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. © 2018 Elsevier Inc.-
dc.languageeng-
dc.publisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/metabol-
dc.relation.ispartofMetabolism-
dc.subject7,8-Dihydroxyflavone-
dc.subjectMitochondrial-
dc.subjectObesity-
dc.subjectSkeletal muscle-
dc.titleBDNF mimetic alleviates body weight gain in obese mice by enhancing mitochondrial biogenesis in skeletal muscle-
dc.typeArticle-
dc.identifier.emailTse, CL: tsecl@hku.hk-
dc.identifier.emailZaw, AM: aungmoe@HKUCC-COM.hku.hk-
dc.identifier.emailChow, BKC: bkcc@hku.hk-
dc.identifier.emailLee, CW: chiwai.lee@hku.hk-
dc.identifier.emailChan, CB: chancb@hku.hk-
dc.identifier.authorityChow, BKC=rp00681-
dc.identifier.authorityLee, CW=rp02089-
dc.identifier.authorityChan, CB=rp02140-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.metabol.2018.06.007-
dc.identifier.pmid29935237-
dc.identifier.scopuseid_2-s2.0-85050402133-
dc.identifier.hkuros286108-
dc.identifier.volume87-
dc.identifier.spage113-
dc.identifier.epage122-
dc.identifier.isiWOS:000454746800015-
dc.publisher.placeUnited States-

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