Linking nutritional regulation of Angptl4, Gpihbp1, and Lmf1 to lipoprotein lipase activity in rodent adipose tissue

The system underwent moderate circadian oscillations, for LPL in phase with food intake, for ANGPTL4 and GPIHBP1 in the opposite direction. Studies with cycloheximide showed that whereas LPL protein turns over rapidly, ANGPTL4 protein turns over more slowly. Studies with the transcription blocker Actinomycin D showed that transcripts for ANGPTL4 and GPIHBP1, but not LMF1 or LPL, turn over rapidly. When food was withdrawn the expression of ANGPTL4 and GPIHBP1 increased rapidly, and LPL activity decreased. On re-feeding and after injection of insulin the expression of ANGPTL4 and GPIHBP1 decreased rapidly, and LPL activity increased. In ANGPTL4？/？ mice adipose tissue LPL activity did not show these responses. In old, obese rats that showed signs of insulin resistance, the responses of ANGPTL4 and GPIHBP1 mRNA and of LPL activity were severely blunted (at 26？weeks of age) or almost abolished (at 52？weeks of age).This study demonstrates directly that ANGPTL4 is necessary for rapid modulation of LPL activity in adipose tissue. ANGPTL4 message levels responded very rapidly to changes in the nutritional state. LPL activity always changed in the opposite direction. This did not happen in Angptl4？/？ mice. GPIHBP1 message levels also changed rapidly and in the same direction as ANGPTL4, i.e. increased on fasting when LPL activity decreased. This was unexpected because GPIHBP1 is known to stabilize LPL. The plasticity of the LPL system is severely blunted or completely lost in insulin resistant rats.Lipoprotein lipase (LPL) is produced by parenchymal cells in some tissues (e.g. adipocytes, myocytes), secreted, and transported to the luminal side of capillaries. Here the enzyme hydrolyzes triglycerides in chylomicrons and VLDL and thereby makes fatty acids available for tissue metabolism. LPL activity is rapidly modulated by the nutritional state and plays a major role in distribution of fatty acids between tissues [1,2] .The rapid daily modulations of LPL activity are mainly p