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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
9th 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.
Hermona Soreq, Biochem Mol biol J, 3:2
DOI: 10.21767/2471-8084-C1-002