학술논문
Profiling mouse brown and white adipocytes to identify metabolically relevant small ORFs and functional microproteins.
Document Type
Academic Journal
Author
Martinez TF; Department of Pharmaceutical Sciences, Department of Biological Chemistry, Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA, USA.; Lyons-Abbott S; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; Bookout AL; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; De Souza EV; Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF) and Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90616-900, Brazil; Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA, USA.; Donaldson C; Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA, USA.; Vaughan JM; Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA, USA.; Lau C; Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA, USA.; Abramov A; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; Baquero AF; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; Baquero K; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; Friedrich D; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; Huard J; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; Davis R; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; Kim B; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; Koch T; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; Mercer AJ; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; Misquith A; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; Murray SA; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; Perry S; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; Pino LK; Department of Genome Sciences, University of Washington, Seattle, WA, USA.; Sanford C; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; Simon A; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; Zhang Y; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; Zipp G; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; Bizarro CV; Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF) and Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90616-900, Brazil.; Shokhirev MN; Razavi Newman Integrative Genomics and Bioinformatics Core, Salk Institute for Biological Studies, La Jolla, CA, USA.; Whittle AJ; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA.; Searle BC; Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA.; MacCoss MJ; Department of Genome Sciences, University of Washington, Seattle, WA, USA.; Saghatelian A; Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA, USA. Electronic address: asaghatelian@salk.edu.; Barnes CA; Novo Nordisk Research Center Seattle, Inc., Seattle, WA, USA; Velia Therapeutics, Inc., San Diego, CA, USA. Electronic address: chrisb@rnes.pro.
Source
Publisher: Cell Press Country of Publication: United States NLM ID: 101233170 Publication Model: Print Cited Medium: Internet ISSN: 1932-7420 (Electronic) Linking ISSN: 15504131 NLM ISO Abbreviation: Cell Metab Subsets: MEDLINE
Subject
Language
English
Abstract
Microproteins (MPs) are a potentially rich source of uncharacterized metabolic regulators. Here, we use ribosome profiling (Ribo-seq) to curate 3,877 unannotated MP-encoding small ORFs (smORFs) in primary brown, white, and beige mouse adipocytes. Of these, we validated 85 MPs by proteomics, including 33 circulating MPs in mouse plasma. Analyses of MP-encoding mRNAs under different physiological conditions (high-fat diet) revealed that numerous MPs are regulated in adipose tissue in vivo and are co-expressed with established metabolic genes. Furthermore, Ribo-seq provided evidence for the translation of Gm8773, which encodes a secreted MP that is homologous to human and chicken FAM237B. Gm8773 is highly expressed in the arcuate nucleus of the hypothalamus, and intracerebroventricular administration of recombinant mFAM237B showed orexigenic activity in obese mice. Together, these data highlight the value of this adipocyte MP database in identifying MPs with roles in fundamental metabolic and physiological processes such as feeding.
Competing Interests: Declaration of interests All authors affiliated with the Novo Nordisk Research Center Seattle, Inc. have worked for a for-profit commercial pharmaceuticals company that produces and sells medicines for the treatment of obesity and diabetes. B.C.S. is a founder and shareholder of Proteome Software. M.J.M. has a sponsored research agreement with and is a paid consultant for Thermo Fisher Scientific. A. Saghatelian is a paid consultant and shareholder for and cofounder of Exo Therapeutics and Velia Therapeutics. T.F.M. is a paid consultant and shareholder of Velia Therapeutics. C.A.B. is a current employee of Velia Therapeutics.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of interests All authors affiliated with the Novo Nordisk Research Center Seattle, Inc. have worked for a for-profit commercial pharmaceuticals company that produces and sells medicines for the treatment of obesity and diabetes. B.C.S. is a founder and shareholder of Proteome Software. M.J.M. has a sponsored research agreement with and is a paid consultant for Thermo Fisher Scientific. A. Saghatelian is a paid consultant and shareholder for and cofounder of Exo Therapeutics and Velia Therapeutics. T.F.M. is a paid consultant and shareholder of Velia Therapeutics. C.A.B. is a current employee of Velia Therapeutics.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)