The fasting-induced adipose factor/angiopoietin-like protein 4 is physically associated with lipoproteins and governs plasma lipid levels and adiposity
Open accessAbstract
Proteins secreted from adipose tissue are increasingly recognized to play an important role in the regulation of glucose metabolism. However, much less is known about their effect on lipid metabolism. The fasting-induced adipose factor (FIAF/angiopoietin-like protein 4/peroxisome proliferator-activated receptor gamma angiopoietin-related protein) was previously identified as a target of hypolipidemic fibrate drugs and insulin-sensitizing thiazolidinediones. Using transgenic mice that mildly overexpress FIAF in peripheral tissues we show that FIAF is an extremely powerful regulator of lipid metabolism and adiposity. FIAF overexpression caused a 50% reduction in adipose tissue weight, partly by stimulating fatty acid oxidation and uncoupling in fat. In addition, FIAF overexpression increased plasma levels of triglycerides, free fatty acids, glycerol, total cholesterol, and high density lipoprotein (HDL)-cholesterol. Functional tests indicated that FIAF overexpression severely impaired plasma triglyceride clearance but had no effect on very low density lipoprotein production. The effects of FIAF overexpression were amplified by a high fat diet, resulting in markedly elevated plasma and liver triglycerides, plasma free fatty acids, and plasma glycerol levels, and impaired glucose tolerance in FIAF transgenic mice fed a high fat diet. Remarkably, in mice the full-length form of FIAF was physically associated with HDL, whereas truncated FIAF was associated with low density lipoprotein. In human both full-length and truncated FIAF were associated with HDL. The composite data suggest that via physical association with plasma lipoproteins, FIAF acts as a powerful signal from fat and other tissues to prevent fat storage and stimulate fat mobilization. Our data indicate that disturbances in FIAF signaling might be involved in dyslipidemia.
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Both FGF21 and ANGPTL4 induce WAT lipolysis.
“While both FGF21 [166] and ANGPTL4 [176,177] induce WAT lipolysis (4)”
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- Authors
- Mandard, S., Zandbergen, F., van Straten, E., Wahli, W., Kuipers, F., Müller, M., & Kersten, S.
- Affiliations
- Wageningen University & Research (NL)
- University of Lausanne (CH)
- University Medical Center Groningen (NL)
- Corresponding author
- Kersten, Sander
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 281
- Issue
- 2
- Pages
- 934-944
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2108629423
- Cited by
- 433
- References
- 38
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 17 · 2023: 14 · 2022: 25 · 2021: 23 · 2020: 29 · 2019: 21 · 2018: 22 · 2017: 21 · 2016: 18 · 2015: 22 · 2014: 37 · 2013: 30 · 2012: 28
- FWCI
- 7.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion)
- IRIS (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- FIAF, ANGPTL4, lipoprotein binding, HDL cholesterol, lipid metabolism, adiposity, fatty acid oxidation, uncoupling, high-fat diet, glucose tolerance, dyslipidemia, transgenic mice, thiazolidinediones
- MeSH terms
- Angiopoietin-Like Protein 4, Adipose Tissue, Animals, Blood Proteins, Body Weight, Cholesterol, Fats, Glucose, Glucose Tolerance Test, Humans, Hypercholesterolemia, Insulin, Lipase, Lipids, Lipoproteins, Lipoproteins, HDL, Lipoproteins, LDL, Lipoproteins, VLDL, Liver, Male, Mice, Transgenic, Models, Genetic, Protein Binding, RNA, Messenger, Time Factors, Triglycerides, Immunoblotting, Signal Transduction, Up-Regulation, Gene Expression, Oligonucleotide Array Sequence Analysis, Angiopoietins, 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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