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Evolutionarily conserved gene family important for fat storage
Open accessAbstract
The ability to store fat in the form of cytoplasmic triglyceride droplets is conserved from Saccharomyces cerevisiae to humans. Although much is known regarding the composition and catabolism of lipid droplets, the molecular components necessary for the biogenesis of lipid droplets have remained obscure. Here we report the characterization of a conserved gene family important for lipid droplet formation named fat-inducing transcript (FIT). FIT1 and FIT2 are endoplasmic reticulum resident membrane proteins that induce lipid droplet accumulation in cell culture and when expressed in mouse liver. shRNA silencing of FIT2 in 3T3-LI adipocytes prevents accumulation of lipid droplets, and depletion of FIT2 in zebrafish blocks diet-induced accumulation of lipid droplets in the intestine and liver, highlighting an important role for FIT2 in lipid droplet formation in vivo. Together these studies identify and characterize a conserved gene family that is important in the fundamental process of storing fat.
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“For instance, in vitro FIT2 overexpression promoted LD accumulation in human embryonic kidney 293 cells, while FIT2 knockdown reduced TG levels and LD accumulation in mouse adipocytes (58).”
From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [58]
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“Since FIT2 is primarily involved in TG-mediated LD development (58), sterol esters might still contribute to LD formation without this FIT isoform.”
From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [58]
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Metadata
- Authors
- Kadereit, B., Kumar, P., Wang, W.-J., Miranda, D., Snapp, E. L., Severina, N., Torregroza, I., Evans, T., & Silver, D. L.
- Affiliations
- *Department of Biochemistry and the Marion Bessin Liver Research Center and
- Albert Einstein College of Medicine (US)
- University of California, San Francisco (US)
- Corresponding author
- Silver, David L.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-01-08
- Volume
- 105
- Issue
- 1
- Pages
- 94-99
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2224239
- OpenAlex
- W2163138997
- Cited by
- 252
- References
- 37
- Citations by year
- 2026: 12 · 2025: 7 · 2024: 9 · 2023: 13 · 2022: 23 · 2021: 15 · 2020: 15 · 2019: 17 · 2018: 22 · 2017: 15 · 2016: 10 · 2015: 13 · 2014: 12 · 2013: 9 · 2012: 12
- FWCI
- 4.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (DK41296)
- National Institute on Aging (R21AG032544)
- National Heart, Lung, and Blood Institute (R01HL064282)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK41296, P30DK041296)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- lipid droplet formation, fat deposition, endoplasmic reticulum membrane protein, adipocytes, zebrafish, mouse liver
- MeSH terms
- Adipose Tissue, Amino Acid Sequence, Animals, Diabetes Mellitus, Experimental, Gene Expression Regulation, Humans, Lipids, Liver, Membrane Proteins, Models, Biological, Molecular Sequence Data, Triglycerides, Zebrafish, Conserved Sequence, Sequence Homology, Amino Acid, Adipocytes, Evolution, Molecular, 3T3-L1 Cells, Mice
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