COVID-19 Response: Local Logistics     National Effort

Loss of Hepatic Oscillatory Fed microRNAs Abrogates Refed Transition and Causes Liver Dysfunctions [Next Gen Genomics Facility].

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TitleLoss of Hepatic Oscillatory Fed microRNAs Abrogates Refed Transition and Causes Liver Dysfunctions [Next Gen Genomics Facility].
Publication TypeJournal Article
Year of Publication2019
AuthorsManiyadath B, Chattopadhyay T, Verma S, Kumari S, Kulkarni P, Banerjee K, Lazarus A, Kokane SS, Shetty T, Anamika K, Kolthur-Seetharam U
JournalCell Rep
Volume26
Issue8
Pagination2212-2226.e7
Date Published2019 Feb 19
ISSN2211-1247
Abstract

Inability to mediate fed-fast transitions in the liver is known to cause metabolic dysfunctions and diseases. Intuitively, a failure to inhibit futile translation of state-specific transcripts during fed-fast cycles would abrogate dynamic physiological transitions. Here, we have discovered hepatic fed microRNAs that target fasting-induced genes and are essential for a refed transition. Our findings highlight the role of these fed microRNAs in orchestrating system-level control over liver physiology and whole-body energetics. By targeting SIRT1, PGC1α, and their downstream genes, fed microRNAs regulate metabolic and mitochondrial pathways. MicroRNA expression, processing, and RISC loading oscillate during these cycles and possibly constitute an anticipatory mechanism. Fed-microRNA oscillations are deregulated during aging. Scavenging of hepatic fed microRNAs causes uncontrolled gluconeogenesis and failure in the catabolic-to-anabolic switching upon feeding, which are hallmarks of metabolic diseases. Besides identifying mechanisms that enable efficient physiological toggling, our study highlights fed microRNAs as candidate therapeutic targets.

DOI10.1016/j.celrep.2019.01.087
Alternate JournalCell Rep
PubMed ID30784600