ArticleMolecular metabolism2022
Angiopoietin-like 4 governs diurnal lipoprotein lipase activity in brown adipose tissue.
Article in Molecular metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 13 citations in OpenAlex.
- The Anti-obesity Effects of Lotus (Nelumbo nucifera Gaertn.) Seed Red Skin (Testa) Catechins by Regulating Lipoprotein Lipase Expression and Activity.Plant foods for human nutrition (Dordrecht, Netherlands) · 2025Article
- Circadian Disruption and the Risk of Developing Obesity.Current obesity reports · 2025Review
- The role of brain-liver-gut Axis in neurological disorders.Burns & trauma · 2025Review
- Liver-targeted Angptl4 silencing by antisense oligonucleotide treatment attenuates hyperlipidaemia and atherosclerosis development in APOE*3-Leiden.CETP mice.Cardiovascular research · 2024Article
- Chromatin Immunoprecipitation in Adipose Tissue and Adipocytes: How to Proceed and Optimize the Protocol for Transcription Factor DNA Binding.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Gut liver brain axis in diseases: the implications for therapeutic interventions.Signal transduction and targeted therapy · 2023Review
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveBrown adipose tissue (BAT) burns fatty acids (FAs) to produce heat, and shows diurnal oscillation in glucose and triglyceride (TG)-derived FA-uptake, peaking around wakening. Here we aimed to gain insight in the diurnal regulation of metabolic BAT activity.
methodsRNA-sequencing, chromatin immunoprecipitation (ChIP)-sequencing, and lipidomics analyses were performed on BAT samples of wild type C57BL/6J mice collected at 3-hour intervals throughout the day. Knockout and overexpression models were used to study causal relationships in diurnal lipid handling by BAT.
resultsWe identified pronounced enrichment of oscillating genes involved in extracellular lipolysis in BAT, accompanied by oscillations of FA and monoacylglycerol content. This coincided with peak lipoprotein lipase (Lpl) expression, and was predicted to be driven by peroxisome proliferator-activated receptor gamma (PPARγ) activity. ChIP-sequencing for PPARγ confirmed oscillation in binding of PPARγ to Lpl. Of the known LPL-modulators, angiopoietin-like 4 (Angptl4) showed the largest diurnal amplitude opposite to Lpl, and both Angptl4 knockout and overexpression attenuated oscillations of LPL activity and TG-derived FA-uptake by BAT.
conclusionsOur findings highlight involvement of PPARγ and a crucial role of ANGPTL4 in mediating the diurnal oscillation of TG-derived FA-uptake by BAT, and imply that time of day is essential when targeting LPL activity in BAT to improve metabolic health.
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