Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pbio.1002597
Title: Narciclasine attenuates diet-induced obesity by promoting oxidative metabolism in skeletal muscle
Authors: Julien S.G.
Kim S.-Y.
Brunmeir R. 
Sinnakannu J.R. 
Ge X.
Li H.
Ma W.
Yaligar J.
Bhanu Prakash K.N.
Velan S.S. 
R�der P.V.
Zhang Q.
Sim C.K.
Wu J.
Garcia-Miralles M. 
Pouladi M.A. 
Xie W.
McFarlane C.
Han W. 
Xu F. 
Keywords: adenine nucleotide translocase
cyclic AMP
hydroxymethylglutaryl coenzyme A reductase kinase
narciclasine
reactive oxygen metabolite
adenosine diphosphate
adenosine triphosphate
Amaryllidaceae alkaloid
biological marker
cyclic AMP
fatty acid
hydroxymethylglutaryl coenzyme A reductase kinase
narciclasine
phenanthridine derivative
protective agent
reactive oxygen metabolite
aerobic metabolism
animal cell
animal tissue
Article
blood cell
cell metabolism
controlled study
diet induced obesity
drug effect
energy expenditure
enzyme activation
enzyme synthesis
fatty acid oxidation
glycolysis
human
human tissue
in vitro study
lipid metabolism
male
metabolic clearance
mitochondrial membrane potential
mitochondrial respiration
mouse
muscle cell
myotube
nonhuman
physical activity
protein blood level
signal transduction
skeletal muscle
adverse effects
animal
animal experiment
C57BL mouse
cell culture
cell respiration
diet
drug effects
energy metabolism
lipid diet
metabolism
mitochondrion
obesity
oxidation reduction reaction
skeletal muscle
skeletal muscle cell
slow muscle fiber
Adenosine Diphosphate
Adenosine Triphosphate
Amaryllidaceae Alkaloids
AMP-Activated Protein Kinases
Animals
Biomarkers
Cell Respiration
Cells, Cultured
Cyclic AMP
Diet
Diet, High-Fat
Energy Metabolism
Enzyme Activation
Fatty Acids
Humans
Male
Membrane Potential, Mitochondrial
Mice
Mice, Inbred C57BL
Mitochondria
Muscle Fibers, Skeletal
Muscle Fibers, Slow-Twitch
Muscle, Skeletal
Obesity
Oxidation-Reduction
Phenanthridines
Physical Conditioning, Animal
Protective Agents
Reactive Oxygen Species
Signal Transduction
Issue Date: 2017
Citation: Julien S.G., Kim S.-Y., Brunmeir R., Sinnakannu J.R., Ge X., Li H., Ma W., Yaligar J., Bhanu Prakash K.N., Velan S.S., R�der P.V., Zhang Q., Sim C.K., Wu J., Garcia-Miralles M., Pouladi M.A., Xie W., McFarlane C., Han W., Xu F. (2017). Narciclasine attenuates diet-induced obesity by promoting oxidative metabolism in skeletal muscle. PLoS Biology 15 (2) : e1002597. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pbio.1002597
Rights: Attribution 4.0 International
Abstract: Obesity develops when caloric intake exceeds metabolic needs. Promoting energy expenditure represents an attractive approach in the prevention of this fast-spreading epidemic. Here, we report a novel pharmacological strategy in which a natural compound, narciclasine (ncls), attenuates diet-induced obesity (DIO) in mice by promoting energy expenditure. Moreover, ncls promotes fat clearance from peripheral metabolic tissues, improves blood metabolic parameters in DIO mice, and protects these mice from the loss of voluntary physical activity. Further investigation suggested that ncls achieves these beneficial effects by promoting a shift from glycolytic to oxidative muscle fibers in the DIO mice thereby enhancing mitochondrial respiration and fatty acid oxidation (FAO) in the skeletal muscle. Moreover, ncls strongly activates AMPK signaling specifically in the skeletal muscle. The beneficial effects of ncls treatment in fat clearance and AMPK activation were faithfully reproduced in vitro in cultured murine and human primary myotubes. Mechanistically, ncls increases cellular cAMP concentration and ADP/ATP ratio, which further lead to the activation of AMPK signaling. Blocking AMPK signaling through a specific inhibitor significantly reduces FAO in myotubes. Finally, ncls also enhances mitochondrial membrane potential and reduces the formation of reactive oxygen species in cultured myotubes. ? 2017 Julien et al.
Source Title: PLoS Biology
URI: https://scholarbank.nus.edu.sg/handle/10635/161898
ISSN: 15449173
DOI: 10.1371/journal.pbio.1002597
Rights: Attribution 4.0 International
Appears in Collections:Elements
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