Profiling mouse brown and white adipocytes to identify metabolically relevant small ORFs and functional microproteins
Copyright policy )Profiling mouse brown and white adipocytes to identify metabolically relevant small ORFs and functional microproteins
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.
- University of California, Irvine United States
- The Ohio State University United States
- University of California, San Francisco United States
- University of Mary United States
- Salk Institute for Biological Studies United States
data-independent acquisition mass spectrometry, diet-induced obesity, Adipose Tissue, White, Adipocytes, White, White, Medical Biochemistry and Metabolomics, small ORFs, Endocrinology & Metabolism, Mice, Open Reading Frames, Ribo-seq, white adipose tissue, Adipose Tissue, Brown, Genetics, Adipocytes, microproteins, Humans, Animals, Obesity, Micropeptides, Metabolic and endocrine, Nutrition, ribosome profiling, Diabetes, Brown, brown adipose tissue, Adipocytes, Brown, Adipose Tissue, Biochemistry and Cell Biology, secreted microproteins
data-independent acquisition mass spectrometry, diet-induced obesity, Adipose Tissue, White, Adipocytes, White, White, Medical Biochemistry and Metabolomics, small ORFs, Endocrinology & Metabolism, Mice, Open Reading Frames, Ribo-seq, white adipose tissue, Adipose Tissue, Brown, Genetics, Adipocytes, microproteins, Humans, Animals, Obesity, Micropeptides, Metabolic and endocrine, Nutrition, ribosome profiling, Diabetes, Brown, brown adipose tissue, Adipocytes, Brown, Adipose Tissue, Biochemistry and Cell Biology, secreted microproteins
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