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Sci Rep. 2019 Jan 24;9(1):493. doi: 10.1038/s41598-018-36715-3.

ENOblock inhibits the pathology of diet-induced obesity.

Author information

1
New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju, 61005, Republic of Korea.
2
Cell Regeneration Research Center, Department of Cardiology, Cardiovascular Center, Chonnam National University Hospital, 42 Jebong-ro, Dong-gu, Gwangju, 61469, Republic of Korea.
3
Department of Chemistry, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju, 61005, Republic of Korea.
4
Center for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang, 37673, Republic of Korea.
5
Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.
6
New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju, 61005, Republic of Korea. jung@gist.ac.kr.
7
New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju, 61005, Republic of Korea. darren@gist.ac.kr.

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.

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