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Biochem Mol biol J

ISSN: 2471-8084

Volume 3, Issue 2

Metabolomics Conference 2017

August 29-30, 2017 Prague, Czech Republic

9

th

International Conference and Exhibition on

Metabolomics and Systems Biology

Notes:

Page 36

Cholinergic microRNA-132 sheds new light

on the links between psychological stress

and metabolic impairments

Hermona Soreq

The Hebrew University of Jerusalem, Israel

C

holinergic signaling affects both anxiety-related and

metabolic disorders and is continuously subjected

to epigenetic and microRNA (miR) regulation. However,

key anxiety-induced microRNAs may potentiate both

cholinergic-mediated suppression of inflammation and

metabolic syndrome-related processes. Specifically,

genomic, epigenetic and microRNA regulators of

acetylcholine signaling (CholinomiRs) may implement

inherited and/or acquired anxiety-prone states while

acting as inflammatory suppressors, which in peripheral

tissues can shift the balance towards metabolic disorders.

To study the

in vivo

contributions of specific cholinergic

targets to miR-mediated phenotypes, we quantified their

levels in diet-induced obese mice with hepatic steatosis,

diverse nonalcoholic steatohepatitis (NASH) models and

LDLR-/- mice, a model for familial hyperlipidemia. All of

these models displayed hepatic increases of the anxiety-

induced miR-132, accompanied by variable decreases in

multiple miR-132 targets and lipolysis-related transcripts,

and elevations in lipogenesis-related transcripts.

Furthermore, engineered mice over-expressing miR-132

presented severe fatty liver phenotype, multiple miR-132

target decreases and increased body weight, serum LDL/

VLDL, liver triglycerides, and prosteatotic and lipogenesis-

related transcripts. Inversely, injecting diet-induced obese

and LDLR-/- mice with anti-miR-132 oligonucleotides, but

not knockdown of individual miR-132 targets, efficiently

reversed the hepatic miR-132 excess, hepatic steatosis

and hyper-lipidemic phenotype. Our findings identify miR-

132 as an upstream CholinomiR regulator of both anxiety

and hepatic lipid homeostasis, which displays context-

dependent suppression of multiple targets with cumulative

synergistic effects; and call for interrogating cholinergic

impairments as co-regulating causes of anxiety-related

disorders, hepatic steatosis and NASH. Furthermore,

realization of the intriguing cholinergic-mediated tradeoff

between anxiety and metabolic-related phenomena

may offer novel opportunities for re-classifying healthy

and un-healthy anxiety- and metabolic-prone states,

discriminating between causes of stress-related and

metabolic disorders, and cautiously identifying novel

cholinergic biomarkers and management strategies.

Biography

Hermona Soreq was trained at Weizmann Institute of Science and the

Rockefeller University. At Hebrew University of Jerusalem, she holds a

University Slesinger Chair in Molecular Neuroscience and is also a founding

member of the Edmond and Lily Safra Center for Brain Science. Her research

pioneered the application of molecular biology and genomics to the study of

cholinergic signaling, with a recent focus on its microRNA regulation and on

signaling changes in health and in nervous system and metabolic disease. She

is the elected Head of International Organization of Cholinergic Mechanisms,

served as elected Dean of Hebrew University’s Faculty of Science from 2005-

2008, authored hundreds of publications and won numerous awards in Israel.

[email protected]

Hermona Soreq, Biochem Mol biol J, 3:2

DOI: 10.21767/2471-8084-C1-002