NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipose

Stable Identifier
R-HSA-9031528
Type
Pathway
Species
Homo sapiens
Synonyms
LXRs regulate gene expression linked to triglyceride lipolysis in adipose
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Adipose tissue triglycerides (TGs) represent the major energy store of the body. During adipocyte lipolysis triglycerides (TGs) are hydrolyzed into free fatty acids (FFAs) and glycerol by the action of adipose triglyceride lipase (ATGL, encoded by PNPLA2), then hormone-sensitive lipase (HSL), which is activated by glucagon and adrenaline (epinephrine) and inhibited by insulin. Both isoforms of liver X receptor, LXRα (NR1H3) and LXRβ (NR1H2), are expressed in mature mouse and human adipocytes (Juvet LK et al. 2003). Expression of NR1H3 is up-regulated during adipocyte differentiation (Juvet LK et al. 2003; Darimont C et al. 2006). Ligand activation of LXRs (NR1H2 or NR1H3) can induce adipocyte lipolysis and FFA oxidation (Stenson BM et al. 2011; Ross SE et al. 2002). For instance, in mouse 3T3L1 adipocytes and human primary adipocytes, LXR activation led to an increase in basal, but not hormone-stimulated, lipolysis as measured by glycerol release (Ross SE et al. 2002; Stenson BM et al. 2011). Another study showed that administration of synthetic ligands of NR1H2/ NR1H3, T0901317 or GW3965, to mice resulted in smaller adipocytes and increased serum free fatty acid and glycerol concentrations, suggesting increased adipocyte lipolysis (Commerford SR et al. 2007). Further, microarray analysis of human adipocytes following NR1H3 or NR1H2 activation revealed altered gene expression of several lipolysis-regulating proteins such as perilipin1 (PLIN1), which was also confirmed by quantitative real-time PCR (Stenson BM et al. 2011). Selective knockdown of either NR1H2 or NR1H3 showed that NR1H3 (LXRα) was the major isoform mediating the lipolysis-related effects of LXR agonists (Stenson BM et al. 2011). In addition, the absence of NR1H3 (LXRα) in mouse adipose tissue resulted in elevated adiposity through a decrease of both lipolytic and oxidative capacities in white adipose tissue (Dib L et al. 2014).

Literature References
PubMed ID Title Journal Year
21030586 Liver X receptor (LXR) regulates human adipocyte lipolysis

Stenson, BM, Rydén, M, Venteclef, N, Dahlman, I, Pettersson, AM, Mairal, A, Aström, G, Blomqvist, L, Wang, V, Jocken, JW, Clément, K, Langin, D, Arner, P, Laurencikiene, J

J. Biol. Chem. 2011
22370853 Liver X receptors and fat cell metabolism

Laurencikiene, J, Rydén, M

Int J Obes (Lond) 2012
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