title: Dietary luteolin activates browning and thermogenesis in mice through an AMPK/PGC1α pathway-mediated mechanism.
abstract: Two brown-like adipocytes, including classical brown adipocytes from brown adipose tissues and beige cells from white adipose tissues, regulate thermogenesis. The developmental and functional induction of brown-like cells provides a defense against obesity and associated metabolic diseases. Our previous study suggests dietary luteolin can improve diet-induced obesity and insulin resistance in mice. Here we further elucidated the action of the natural flavonoid on energy expenditure and adaptive thermogenesis.
  
  
  
  Five-week-old male C57BL/6 mice were fed low-fat diet (LFD), high-fat diet (HFD) and HFD supplemented with 0.01% luteolin. After 12 weeks, their energy expenditure were detected using a combined indirect calorimetry system. Moreover, thermogenic program and associated molecular regulators were assessed in adipose tissues. In another independent study, even-aged mice were fed LFD and luteolin-containing LFD for 12 weeks, and their energy expenditure and thermogenic program were also investigated. Finally, differentiated primary brown and subcutaneous adipocytes were used to identify the critical participation of AMPK/PGC1α signaling in luteolin-regulated browning and thermogenesis.
  
  
  
  In mice fed either HFD or LFD, dietary luteolin supplement increased oxygen consumption, carbon dioxide production and respiratory exchange ratio. The enhancement in energy expenditure was accompanied by the upregulation of thermogenic genes in brown and subcutaneous adipose tissues. Meanwhile, several important AMPK/PGC1α signaling molecules were activated by dietary luteolin in the tissues. Further, luteolin treatment directly elevated thermogenic gene expressions and activated AMPK/PGC1α signaling in differentiated primary brown and subcutaneous adipocytes, whereas AMPK inhibitor Compound C reversed the efficiencies.
  
  
  
  Dietary luteolin activated browning and thermogenesis through an AMPK/PGC1α pathway-mediated mechanism.
authors.affiliation: Department of Biological Sciences, School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biological Sciences, School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, China.
authors.forename: Q-X
authors.initials: QX
authors.lastname: Zhang
authors.affiliation: Department of Biological Sciences, School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biological Sciences, School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biological Sciences, School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, China.
authors.forename: W
authors.initials: W
authors.lastname: Qu
authors.affiliation: Department of Biological Sciences, School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, China.
authors.forename: B
authors.initials: B
authors.lastname: Bao
authors.affiliation: Department of Biological Sciences, School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, China.
authors.forename: C-A
authors.initials: CA
authors.lastname: Liu
authors.affiliation: Department of Biological Sciences, School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D052437:Adipocytes, Brown / Q000187:drug effects / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000187:drug effects / Q000473:pathology*; D000818:Animals; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D007333:Insulin Resistance; D047311:Luteolin / Q000008:administration & dosage / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D022722:Thermogenesis / Q000187:drug effects / Q000502:physiology*
chemical_list: C548179:Prkaa1 protein, mouse; D055372:AMP-Activated Protein Kinases; D047311:Luteolin