ENOblock inhibits the pathology of diet-induced obesity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Haaglim Cho, Ji-Hyung Lee, JungIn Um, Sunwook Kim, Yukyung Kim, Woong-Hee Kim, Yong Sook Kim, Haushabhau S. Pagire, Jin Hee Ahn, Youngkeun Ahn, Young-Tae Chang, Da-Woon Jung, Darren R. Williams

ABSTRACT

Obesity is a medical condition that impacts on all levels of society and causes numerous comorbidities, such as diabetes, cardiovascular disease, and cancer. We assessed the suitability of targeting enolase, a glycolysis pathway enzyme with multiple, secondary functions in cells, to treat obesity. Treating adipocytes with ENOblock, a novel modulator of these secondary 'moonlighting' functions of enolase, suppressed the adipogenic program and induced mitochondrial uncoupling. Obese animals treated with ENOblock showed a reduction in body weight and increased core body temperature. Metabolic and inflammatory parameters were improved in the liver, adipose tissue and hippocampus. The mechanism of ENOblock was identified as transcriptional repression of master regulators of lipid homeostasis (Srebp-1a and Srebp-1c), gluconeogenesis (Pck-1) and inflammation (Tnf-α and Il-6). ENOblock treatment also reduced body weight gain, lowered cumulative food intake and increased fecal lipid content in mice fed a high fat diet. Our results support the further drug development of ENOblock as a therapeutic for obesity and suggest enolase as a new target for this disorder. More... »

PAGES

493

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-018-36715-3

    DOI

    http://dx.doi.org/10.1038/s41598-018-36715-3

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111637618

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30679508


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