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dc.contributor.authorLiang, Wentaoen_US
dc.date.accessioned2015-08-05T00:50:43Z
dc.date.available2015-08-05T00:50:43Z
dc.date.issued2012
dc.date.submitted2012
dc.identifier.other(ALMA)contemp
dc.identifier.urihttps://hdl.handle.net/2144/12479
dc.descriptionThesis (M.A.)--Boston Universityen_US
dc.description.abstractMyostatin is a cytokine primarily expressed in skeletal muscle and heart muscle and acts as a negative regulator for muscle development. Inhibition of myostatin by genetic and pharmacological approaches improves metabolic health, which has been generally considered as secondary to the hypermuscularity and insulin hyper-sensitivity. Although the receptor for myostatin is ubiquitously expressed, whether and how myostatin interacts with other metabolically important cell types remain largely unknown. In this work, we provide multiple lines of evidence that myostatin directly interacts with hepatocytes. Furthermore, we show for the first time that myostatin enhances insulin signaling in both cultured hepatocytes and in mouse liver. Mice injected with adena-associated virus encoding myostatin propeptide, an endogenous myostatin inhibitor, were partially protected from diet-induced liver fat accumulation and reduced lipogenic gene expression. Consistent with the in vivo findings, increased lipid accumulation was found in cells treated with myostatin peptide or transfected with myostatin construct. Myostatin promotes the lipogenic effect of insulin by enhancing nuclear translocation of SREBP-1c, the master lipogenic transcription factor and increases expression of its downstream target genes. This effect was found to be associated with myostatin-related mTOR activation. Blocking mTOR activation by rapamycin prevents myostatinassociated increase of nuclear SREBP-1 c and its downstream lipogenic enzymes. In summary, this work identified liver as a direct target of myostatin, providing the first evidence that myostatin has opposite impacts on insulin signaling in muscle cells and hepatocytes. Our data also provided a novel mechanism for the long-term metabolic protection afforded by anti-myostatin treatments demonstrated in this work as well as elsewhere.en_US
dc.language.isoen_US
dc.publisherBoston Universityen_US
dc.rightsThis work is being made available in OpenBU by permission of its author, and is available for research purposes only. All rights are reserved to the author.en_US
dc.titleMyostatin promotes liver fat accumulation through activation of the mTOR-SREBP-1c pathwayen_US
dc.typeThesis/Dissertationen_US
etd.degree.nameMaster of Artsen_US
etd.degree.levelmastersen_US
etd.degree.disciplineMedical Nutrition Sciencesen_US
etd.degree.grantorBoston Universityen_US


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