Abstract
Nuclear receptors, such as the farnesoid X receptor (FXR) and the peroxisome proliferator-activated receptors gamma and alpha (PPAR-γ, -α), are major metabolic regulators in adipose tissue and the liver, where they govern lipid, glucose, and bile acid homeostasis, as well as inflammatory cascades. Glycerol and free fatty acids are the end products of lipid droplet catabolism driven by PPARs. Aquaporins (AQPs), a family of 13 small transmembrane proteins, facilitate the shuttling of water, urea, and/or glycerol. The peculiar role of AQPs in glycerol transport makes them pivotal targets in lipid metabolism, especially considering their tissue-specific regulation by the nuclear receptors PPARγ and PPARα. Here, we review the role of nuclear receptors in the regulation of glycerol shuttling in liver and adipose tissue through the function and expression of AQPs.
Highlights
Glycerol is a necessary constituent of triglyceride (TG) backbones
Since glycerol shuttling mediated by aquaporins and nuclear receptors (NRs) transcriptional activities are strong players in regards to TG and fatty acid metabolism, we review their interplay in this article
The NR superfamily includes 48 transcription factors in humans (49 in mice) [3]; in this review, we mainly focus on the peroxisome proliferator-activated receptors (PPARs), the farnesoid X receptor (FXR), and the liver X receptors (LXRs)
Summary
TGs are the main source of energy storage for the human body, taking part in metabolic processes such as fatty acid oxidation, and the biosynthesis of other lipid molecules and lipoproteins [1]. The regulation of their metabolism is finely tuned by nuclear receptors (NRs), a family of transcriptional regulators involved in diverse functions such as glucose metabolism, lipid homeostasis, and development [2]. Aquaporins are a family of membrane water channels, which are involved in a wide range of physiological functions and diseases They mediate osmotic water transport across cell plasma membranes and glycerol diffusion, regulating pivotal physiologic functions such as cell proliferation and lipid metabolism. Since glycerol shuttling mediated by aquaporins and NR transcriptional activities are strong players in regards to TG and fatty acid metabolism, we review their interplay in this article
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