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Updated: Aug 15, 2025
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Isolating Brown Adipocytes from Murine Interscapular Brown Adipose Tissue for Gene and Protein Expression Analysis
Published on: March 12, 2021
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Profiling mouse brown and white adipocytes to identify metabolically relevant small ORFs and functional microproteins
Thomas F Martinez1, Sally Lyons-Abbott2, Angie L Bookout2
1Department of Pharmaceutical Sciences, Department of Biological Chemistry, Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA, USA.
Cell Metabolism
|January 4, 2023
Summary
Researchers identified 3,877 novel microproteins (MPs) in mouse fat cells using ribosome profiling. One microprotein, Gm8773 (mFAM237B), was found to stimulate feeding in obese mice, highlighting MPs
Area of Science:
- Metabolomics and Proteomics
- Molecular Biology
- Endocrinology
Background:
- Microproteins (MPs) represent an understudied class of proteins with potential roles in metabolic regulation.
- Small open reading frames (smORFs) encoding MPs are often overlooked in genomic and proteomic studies.
- Adipose tissue is a key endocrine organ involved in energy homeostasis and metabolic regulation.
Purpose of the Study:
- To systematically identify and characterize novel microproteins (MPs) encoded by small open reading frames (smORFs) in mouse adipocytes.
- To investigate the physiological relevance and potential metabolic functions of identified MPs, particularly in adipose tissue and the central nervous system.
- To discover novel regulators of feeding behavior and energy balance.
Main Methods:
- Ribosome profiling (Ribo-seq) was employed to identify actively translated smORFs in primary brown, white, and beige mouse adipocytes.
- Proteomics was used to validate the expression and detect circulating MPs in mouse plasma.
- Quantitative PCR and in vivo studies (high-fat diet, intracerebroventricular administration) were performed to assess MP regulation and function.
Main Results:
- A comprehensive database of 3,877 unannotated MP-encoding smORFs was curated from mouse adipocytes.
- Eighty-five MPs were validated by proteomics, including 33 found in mouse plasma, suggesting potential endocrine roles.
- The microprotein Gm8773 (mFAM237B), highly expressed in the hypothalamus, demonstrated orexigenic (appetite-stimulating) activity in obese mice.
Conclusions:
- This study establishes a valuable resource of adipocyte-derived microproteins, expanding the known proteome.
- Numerous identified MPs are regulated in adipose tissue and co-expressed with known metabolic genes, indicating their involvement in metabolic processes.
- The discovery of Gm8773's orexigenic function highlights the potential of microproteins as novel regulators of feeding behavior and therapeutic targets for obesity.
