Metabolic functions of FABPs—mechanisms and therapeutic implications
Open accessAbstract
Intracellular and extracellular interactions with proteins enables the functional and mechanistic diversity of lipids. Fatty acid-binding proteins (FABPs) were originally described as intracellular proteins that can affect lipid fluxes, metabolism and signalling within cells. As the functions of this protein family have been further elucidated, it has become evident that they are critical mediators of metabolism and inflammatory processes, both locally and systemically, and therefore are potential therapeutic targets for immunometabolic diseases. In particular, genetic deficiency and small molecule-mediated inhibition of FABP4 (also known as aP2) and FABP5 can potently improve glucose homeostasis and reduce atherosclerosis in mouse models. Further research has shown that in addition to their intracellular roles, some FABPs are found outside the cells, and FABP4 undergoes regulated, vesicular secretion. The circulating form of FABP4 has crucial hormonal functions in systemic metabolism. In this Review we discuss the roles and regulation of both intracellular and extracellular FABP actions, highlighting new insights that might direct drug discovery efforts and opportunities for management of chronic metabolic diseases.
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“Fatty acid-binding proteins (FABPs) are intracellular chaperones of long-chain fatty acids that regulate lipid metabolism, signal transduction, and gene expression [7, 8].”
- Authors
- Hotamisligil, G. S., & Bernlohr, D. A.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Bernlohr, David A.
- ORCID
- Bernlohr, David A.
- Venue
- Nature Reviews Endocrinology
- Published
- 2015-08-11
- Volume
- 11
- Issue
- 10
- Pages
- 592-605
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- PMC
- PMC4578711
- OpenAlex
- W1872721533
- Semantic Scholar
- 758eca5eaf7eb1dad1f5ec48b64f67b92c2c21ea
- Cited by
- 712
- References
- 179
- Citations by year
- 2026: 71 · 2025: 104 · 2024: 88 · 2023: 73 · 2022: 74 · 2021: 77 · 2020: 56 · 2019: 56 · 2018: 41 · 2017: 49 · 2016: 21 · 2015: 2
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Union Chimique Belge
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK064360, DK053189, R01DK064360, R56DK064360, R56DK053189, R01DK053189)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- fatty acid binding protein, FABP4, FABP5, AP-2, fatty acid metabolism, obesity, adipose tissue, glucose homeostasis, atherosclerosis, vesicular secretion, therapeutic target, lipid signaling, inflammation
- MeSH terms
- Animals, Humans, Inflammation, Gene Expression, Lipid Metabolism, Fatty Acid-Binding Proteins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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