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    Freeze dried broccoli extract relieves ER stress and mitochondrial inefficiency in differentiated human pre-adipocyte cells

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    Authors
    Murphy, A
    Jackisch, L.
    Azharian, S
    Aladel, A
    Barker, G
    Tripathi, G
    Chappell, M
    McTernan, P
    Affiliation
    University of Westminster
    Issue Date
    01/03/2014
    
    Metadata
    Show full item record
    Abstract
    In obesity, excess nutrients can disrupt protein folding in the endoplasmic reticulum (ER) which activates the unfolded protein response (UPR) and alters mitochondrial function. These changes can induce inflammation, oxidative stress and insulin resistance. The aim of the study was to investigate whether broccoli extract can protect against cellular damage in human adipocytes, which with mathematical modelling may help predict pathway response. Differentiated Chub-S7 cells were treated over a 72 hr time course with 10 ng/ml freeze-dried broccoli extract (hybrid Brassica oleracea var. italic) alone or combined with ER stress inducer, tunicamycin (750 ng/ml). UPR markers (ATF6, ATF4, CHOP, ERO1α, P-PERK, PERK, P-eIF2α, eIF2α, P-IRE1α and IRE1α) were measured by qRT-PCR and Western blot. Mitochondrial genes (MFN2, OPA1, UCP2, SOD2, POLG) were also measured. Mathematical modelling was undertaken. Tunicamycin led to a significant increase in UPR gene expression (P<0.05), whilst broccoli extract combined with tunicamycin significantly reduced the expression of UPR markers compared with those treated only with tunicamycin, in a time dependent manner. Tunicamycin had a detrimental effect on mitochondrial genes (P<0.05); the presence of broccoli appeared to protect against these effects. This in-vitro time-series data are being used to realistically parameterise an existing mathematical model. Broccoli extract appears to positively influence protein folding in ER stressed adipocytes, reducing UPR gene expression and causing influential changes in mitochondria. As such broccoli supplementation in the daily diet may reduce the inflammatory response posed by adipose tissue during weight gain. The mathematical model of the UPR offers the possibility of in silico optimisation for the supplementation.
    Citation
    Murphy, A., Jackisch, L., Azharian, S., Aladel, A., Barker, G., Tripathi, G., Chappell, M. and McTernan, P. (2016). 'Freeze dried broccoli extract relieves ER stress and mitochondrial inefficiency in differentiated human pre-adipocyte cells. Society for Endocrinology BES 2016. Brighton 07 - 09 Nov. Society for Endocrinology. DOI:10.1530/endoabs.44.P191.
    Publisher
    bioscientifica
    Journal
    Endocrine Abstracts
    URI
    http://hdl.handle.net/10545/624115
    DOI
    10.1530/endoabs.44.P191
    Additional Links
    https://www.endocrine-abstracts.org/ea/0044/ea0044p191.htm
    Type
    Meetings and proceedings
    Language
    en
    ISSN
    14703947
    EISSN
    14796848
    ae974a485f413a2113503eed53cd6c53
    10.1530/endoabs.44.P191
    Scopus Count
    Collections
    School of Human Sciences

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