Angiopoietin-like 4 directs uptake of dietary fat away from adipose during fasting
Open accessAbstract
Angiopoietin-like 4 (ANGPTL4) is a fasting-induced inhibitor of lipoprotein lipase (LPL) and a regulator of plasma triglyceride metabolism. Here, we examined the kinetics of Angptl4 induction and tested the hypothesis that ANGPTL4 functions physiologically to reduce triglyceride delivery to adipose tissue during nutrient deprivation. Gene expression, LPL activity, and triglyceride uptake were examined in fasted and fed wild-type and Angptl4−/− mice. Angptl4 was strongly induced early in fasting, and this induction was suppressed in mice with access to food during the light cycle. Fasted Angptl4−/− mice manifested increased LPL activity and triglyceride uptake in adipose tissue compared to wild-type mice. Angptl4 is induced early in fasting to divert uptake of fatty acids and triglycerides away from adipose tissues.
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ANGPTL4 could selectively inhibit LPL in WAT to redirect FFAs for catabolism in SkM, rather than to their storage in WAT.
“ANGPTL4 could selectively inhibit LPL in WAT to redirect FFAs for catabolism in SkM, rather than to their storage in WAT [197].”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [197]
The Discussion (page unavailable) proposes that ANGPTL4 acts locally in adipose tissue during fasting to inhibit LPL, redirecting triglyceride-derived fatty acids toward heart and muscle rather than adipose storage. It does not establish that those fatty acids are catabolized specifically in skeletal muscle. (LLM, conf=0.85)
Experimental — accuracy not yet measuredANGPTL4 may selectively inhibit WAT LPL to favor lipoprotein-derived FFAs by the exercising SkM.
“the latter may selectively inhibit WAT LPL to favor lipoprotein-derived FFAs by the exercising SkM [197].”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [197]
The Discussion (page unavailable) proposes that ANGPTL4 inhibits adipose LPL during fasting, redirecting triglyceride-derived fatty acids toward tissues including muscle. It does not establish that this adipose mechanism preferentially supplies exercising skeletal muscle; its separate mention of a shift toward exercised muscle does not link that shift to WAT LPL inhibition. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm
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Lipoprotein lipase in mouse kidney: effects of nutritional status and high-fat diet
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Hepatokines, bile acids and ketone bodies are novel Hormones regulating energy homeostasis
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ANGPTL4-the Link Binding Lipid Metabolism and Inflammation
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Adipocyte-Specific ACKR3 Regulates Lipid Levels in Adipose Tissue
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- Authors
- Cushing, E. M., Chi, X., Sylvers, K. L., Shetty, S. K., Potthoff, M. J., & Davies, B. S. J.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Davies, Brandon S.J.
- ORCID
- Venue
- Molecular Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 6
- Issue
- 8
- Pages
- 809-818
- ISSN
- 2212-8778 (ISSN-L)
- PMC
- PMC5518724
- OpenAlex
- W2697923644
- Cited by
- 88
- References
- 44
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 9 · 2023: 7 · 2022: 9 · 2021: 19 · 2020: 16 · 2019: 12 · 2018: 8
- FWCI
- 7.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Metabolism (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health (R01HL130146 [BSJD], R01DK106104 [MJP], T32GM082729 [EMC])
- American Heart Association Scientist Development (12SDG8580004 [BSJD])
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- ANGPTL4, fasting, lipoprotein lipase, triglyceride uptake, adipose tissue, dietary fat, nutrient deprivation, triglyceride metabolism, gene induction, light cycle
- MeSH terms
- Angiopoietin-Like Protein 4, Adipose Tissue, Animals, Dietary Fats, Fasting, Male, Mice, Inbred C57BL, Triglycerides, Mice
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