| First Author | van Eenige R | Year | 2022 |
| Journal | Mol Metab | Volume | 60 |
| Pages | 101497 | PubMed ID | 35413480 |
| Mgi Jnum | J:357308 | Mgi Id | MGI:7265853 |
| Doi | 10.1016/j.molmet.2022.101497 | Citation | van Eenige R, et al. (2022) Angiopoietin-like 4 governs diurnal lipoprotein lipase activity in brown adipose tissue. Mol Metab 60:101497 |
| abstractText | OBJECTIVE: Brown 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. METHODS: RNA-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. RESULTS: We 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 (PPARgamma) activity. ChIP-sequencing for PPARgamma confirmed oscillation in binding of PPARgamma 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. CONCLUSIONS: Our findings highlight involvement of PPARgamma 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. |
