Abstract
Brown adipose tissue (BAT) activation via cold exposure is increasingly scrutinized as a potential approach to ameliorate cardio-metabolic risk. Transition to cold temperatures requires changes in the partitioning of energy substrates, re-routing fatty acids to BAT to fuel non-shivering thermogenesis. However, the mechanisms behind the redistribution of energy substrates to BAT remain largely unknown. Angiopoietin-like 4 (ANGPTL4), a protein that inhibits lipoprotein lipase (LPL) activity, is highly expressed in BAT. Here, we demonstrate that ANGPTL4 is part of a shuttling mechanism that directs fatty acids derived from circulating triglyceride-rich lipoproteins to BAT during cold. Specifically, we show that cold markedly down-regulates ANGPTL4 in BAT, likely via activation of AMPK, enhancing LPL activity and uptake of plasma triglyceride-derived fatty acids. In contrast, cold up-regulates ANGPTL4 in WAT, abolishing a cold-induced increase in LPL activity. Together, our data indicate that ANGPTL4 is an important regulator of plasma lipid partitioning during sustained cold.
Original language | English |
---|---|
Article number | e08428 |
Number of pages | 23 |
Journal | Elife |
Volume | 4 |
DOIs | |
Publication status | Published - 17 Oct 2015 |
Keywords
- ACTIVATED PROTEIN-KINASE
- LIPOPROTEIN-LIPASE
- FATTY-ACIDS
- EXPRESSION
- TARGET
- PLASMA
- P300
- GENE
- PHOSPHORYLATION
- DEFICIENCY