Peroxisomal proliferator-activated receptor α-b deficiency induces the reprogramming of nutrient metabolism in zebrafish
- 1 October 2020
- journal article
- research article
- Published by Wiley in Journal Of Physiology-London
- Vol. 598 (20), 4537-4553
- https://doi.org/10.1113/JP279814
Abstract
Dysfunction of lipid metabolism is involved in the pathogenesis of several chronic metabolic diseases. Peroxisome proliferator-activated receptor alpha (PPAR alpha) is essential for normal metabolic homeostasis and, in particular, for the regulation of fatty acid beta-oxidation (FAO). However, little is known about its regulation roles in systemic nutrient metabolism. To explore the underlying modulation role of PPAR alpha in metabolic homeostasis, we generated apparab-knockout zebrafish (Danio rerio) model. Thepparabmutants demonstrated lower expression of key enzymes involved in FAO, as well as lower mitochondrial and peroxisomal FAO in tissues, which was associated with lipid accumulation in liver and visceral mass. Conversely, glucose utilization was higher because they demonstrated lower blood glucose and tissue glycogen concentrations, as well as activation of the phosphoinositide 3-kinase/AKT pathway. In addition,pparab-deficient zebrafish demonstrated activation of AKT/mammalian target of rapamycin signalling and higher protein content, implying greater protein synthesis and/or lower amino acid breakdown. These data clearly revealed thatpparabdeletion reduces FAO but increases glucose utilization and protein deposition to maintain energy homeostasis. The present study provides new insights into the comprehensive regulatory role of PPAR alpha in systemic energy metabolism in fish, and this pparab-deficient zebrafish also constitutes a valuable model for investigating the functions of PPAR alpha in mammals from comparative physiology aspects.Funding Information
- National Natural Science Foundation of China (31830102, 31772859)
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