title: MicroRNA-16 modulates macrophage polarization leading to improved insulin sensitivity in myoblasts.
abstract: Uncontrolled inflammation leads to several diseases such as insulin resistance, T2D and several types of cancers. The functional role of microRNAs in inflammation induced insulin resistance is poorly studied. MicroRNAs are post-transcriptional regulatory molecules which mediate diverse biological processes. We here show that miR-16 expression levels are down-regulated in different inflammatory conditions such as LPS/IFNγ or palmitate treated macrophages, palmitate exposed myoblasts and insulin responsive tissues of high sucrose diet induced insulin resistant rats. Importantly, forced expression of miR-16 in macrophages impaired the production of TNF-α, IL-6 and IFN-β leading to enhanced insulin stimulated glucose uptake in co-cultured skeletal myoblasts. Further, ectopic expression of miR-16 enhanced insulin stimulated glucose uptake in skeletal myoblasts via the up-regulation of GLUT4 and MEF2A, two key players involved in insulin stimulated glucose uptake. Collectively, our data highlight the important role of miR-16 in ameliorating inflammation induced insulin resistance.
authors.affiliation: Department of Biology, Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India.
authors.forename: Malathi
authors.initials: M
authors.lastname: Talari
authors.affiliation: Department of Biology, Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India.
authors.forename: Bandish
authors.initials: B
authors.lastname: Kapadia
authors.affiliation: Department of Biology, Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India.
authors.forename: Vasundhara
authors.initials: V
authors.lastname: Kain
authors.affiliation: Institute of Science, Nirma University, Sarkhej Gandhinagar Highway, Ahmedabad, Gujarat, India.
authors.forename: Sriram
authors.initials: S
authors.lastname: Seshadri
authors.affiliation: Institute of Science, Nirma University, Sarkhej Gandhinagar Highway, Ahmedabad, Gujarat, India.
authors.forename: Bhumika
authors.initials: B
authors.lastname: Prajapati
authors.affiliation: Institute of Science, Nirma University, Sarkhej Gandhinagar Highway, Ahmedabad, Gujarat, India.
authors.forename: Parth
authors.initials: P
authors.lastname: Rajput
authors.affiliation: Department of Biology, Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India.
authors.forename: Parimal
authors.initials: P
authors.lastname: Misra
authors.affiliation: Department of Biology, Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India. Electronic address: kishorep@drils.org.
authors.forename: Kishore V L
authors.initials: KV
authors.lastname: Parsa
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D016764:Cell Polarity / Q000187:drug effects; D018920:Coculture Techniques; D019422:Dietary Sucrose / Q000009:adverse effects; D015536:Down-Regulation / Q000187:drug effects; D004731:Endotoxins / Q000633:toxicity; D005230:Fatty Acids, Nonesterified / Q000009:adverse effects; D007333:Insulin Resistance; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D032446:Myoblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
chemical_list: D019422:Dietary Sucrose; D004731:Endotoxins; D005230:Fatty Acids, Nonesterified; C547573:MIRN16 microRNA, rat; D035683:MicroRNAs; C522604:Mirn16 microRNA, mouse; D011994:Recombinant Proteins; C044101:endotoxin, Escherichia coli; D007371:Interferon-gamma
keywords: GLUT4; High sucrose diet; Inflammation; Insulin resistance; Macrophage polarization; microRNA